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20 pages, 3797 KiB

Open AccessArticle

SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites

by Guilherme C. Lechuga, Franklin Souza-Silva, Carolina Q. Sacramento, Monique R. O. Trugilho, Richard H. Valente, Paloma Napoleão-Pêgo, Suelen S. G. Dias, Natalia Fintelman-Rodrigues, Jairo R. Temerozo, Nicolas Carels, Carlos R. Alves, Mirian C. S. Pereira, David W. Provance, Jr., Thiago M. L. Souza and Salvatore G. De-Simone

Int. J. Mol. Sci. 2021, 22(16), 9035; https://doi.org/10.3390/ijms22169035 - 21 Aug 2021

Cited by 36 | Viewed by 4851

Abstract

(1) Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to hematological dysfunctions, but there are little experimental data that explain this. Spike (S) and Nucleoprotein (N) proteins have been putatively associated with these dysfunctions. [...] Read more.

(1) Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to hematological dysfunctions, but there are little experimental data that explain this. Spike (S) and Nucleoprotein (N) proteins have been putatively associated with these dysfunctions. In this work, we analyzed the recruitment of hemoglobin (Hb) and other metabolites (hemin and protoporphyrin IX-PpIX) by SARS-Cov2 proteins using different approaches. (2) Methods: shotgun proteomics (LC–MS/MS) after affinity column adsorption identified hemin-binding SARS-CoV-2 proteins. The parallel synthesis of the peptides technique was used to study the interaction of the receptor bind domain (RBD) and N-terminal domain (NTD) of the S protein with Hb and in silico analysis to identify the binding motifs of the N protein. The plaque assay was used to investigate the inhibitory effect of Hb and the metabolites hemin and PpIX on virus adsorption and replication in Vero cells. (3) Results: the proteomic analysis by LC–MS/MS identified the S, N, M, Nsp3, and Nsp7 as putative hemin-binding proteins. Six short sequences in the RBD and 11 in the NTD of the spike were identified by microarray of peptides to interact with Hb and tree motifs in the N protein by in silico analysis to bind with heme. An inhibitory effect in vitro of Hb, hemin, and PpIX at different levels was observed. Strikingly, free Hb at 1mM suppressed viral replication (99%), and its interaction with SARS-CoV-2 was localized into the RBD region of the spike protein. (4) Conclusions: in this study, we identified that (at least) five proteins (S, N, M, Nsp3, and Nsp7) of SARS-CoV-2 recruit Hb/metabolites. The motifs of the RDB of SARS-CoV-2 spike, which binds Hb, and the sites of the heme bind-N protein were disclosed. In addition, these compounds and PpIX block the virus’s adsorption and replication. Furthermore, we also identified heme-binding motifs and interaction with hemin in N protein and other structural (S and M) and non-structural (Nsp3 and Nsp7) proteins. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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15 pages, 4625 KiB

Open AccessArticle

Previous Influenza Infection Exacerbates Allergen Specific Response and Impairs Airway Barrier Integrity in Pre-Sensitized Mice

by Kevin Looi, Alexander N. Larcombe, Kara L. Perks, Luke J. Berry, Graeme R. Zosky, Paul Rigby, Darryl A. Knight, Anthony Kicic and Stephen M. Stick

Int. J. Mol. Sci. 2021, 22(16), 8790; https://doi.org/10.3390/ijms22168790 - 16 Aug 2021

Cited by 5 | Viewed by 1974

Abstract

In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving [...] Read more.

In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving a second ovalbumin sensitization and challenge with saline, ovalbumin (OVA) or house dust mite (HDM). Fifteen days post-infection, bronchoalveolar inflammation, serum antibodies, responsiveness to methacholine and barrier integrity were assessed. There was no effect of infection alone on bronchoalveolar lavage cellular inflammation 15 days post-infection; however, OVA or HDM challenge resulted in increased bronchoalveolar inflammation dominated by eosinophils/neutrophils or neutrophils, respectively. Previously infected mice had higher serum OVA-specific IgE compared with uninfected mice. Mice previously infected, sensitized and challenged with OVA were most responsive to methacholine with respect to airway resistance, while HDM challenge caused significant increases in both tissue damping and tissue elastance regardless of previous infection status. Previous influenza infection was associated with decreased claudin-1 expression in all groups and decreased occludin expression in OVA or HDM-challenged mice. This study demonstrates the importance of the respiratory epithelium in pre-sensitized individuals, where influenza-infection-induced barrier disruption resulted in increased systemic OVA sensitization and downstream effects on lung function. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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18 pages, 1414 KiB

Open AccessArticle

Analysis of DnaK Expression from a Strain of Mycoplasma fermentans in Infected HCT116 Human Colon Carcinoma Cells

by Sabrina Curreli, Hervé Tettelin, Francesca Benedetti, Selvi Krishnan, Fiorenza Cocchi, Marvin Reitz, Robert C. Gallo and Davide Zella

Int. J. Mol. Sci. 2021, 22(8), 3885; https://doi.org/10.3390/ijms22083885 - 09 Apr 2021

Cited by 6 | Viewed by 2522

Abstract

Several species of mycoplasmas, including Mycoplasma fermentans, are associated with certain human cancers. We previously isolated and characterized in our laboratory a strain of human mycoplasma M. fermentans subtype incognitus (MF-I1) able to induce lymphoma in a Severe Combined Immuno-Deficient (SCID) mouse [...] Read more.

Several species of mycoplasmas, including Mycoplasma fermentans, are associated with certain human cancers. We previously isolated and characterized in our laboratory a strain of human mycoplasma M. fermentans subtype incognitus (MF-I1) able to induce lymphoma in a Severe Combined Immuno-Deficient (SCID) mouse model, and we demonstrated that its chaperone protein, DnaK, binds and reduces functions of human poly-ADP ribose polymerase-1 (PARP1) and ubiquitin carboxyl-terminal hydrolase protein-10 (USP10), which are required for efficient DNA repair and proper p53 activities, respectively. We also showed that other bacteria associated with human cancers (including Mycoplasmapneumoniae, Helicobacterpylori, Fusobacteriumnucleatum, Chlamydiathrachomatis, and Chlamydia pneumoniae) have closely related DnaK proteins, indicating a potential common mechanism of cellular transformation. Here, we quantify dnaK mRNA copy number by RT-qPCR analysis in different cellular compartments following intracellular MF-I1 infection of HCT116 human colon carcinoma cells. DnaK protein expression in infected cells was also detected and quantified by Western blot. The amount of viable intracellular mycoplasma reached a steady state after an initial phase of growth and was mostly localized in the cytoplasm of the invaded cells, while we detected a logarithmically increased number of viable extracellular bacteria. Our data indicate that, after invasion, MF-I1 is able to establish a chronic intracellular infection. Extracellular replication was more efficient while MF-I1 cultured in cell-free axenic medium showed a markedly reduced growth rate. We also identified modifications of important regulatory regions and heterogeneous lengths of dnaK mRNA transcripts isolated from intracellular and extracellular MF-I1. Both characteristics were less evident in dnaK mRNA transcripts isolated from MF-I1 grown in cell-free axenic media. Taken together, our data indicate that MF-I1, after establishing a chronic infection in eukaryotic cells, accumulates different forms of dnaK with efficient RNA turnover. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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31 pages, 8262 KiB

Open AccessArticle

Altered microRNA Transcriptome in Cultured Human Liver Cells upon Infection with Ebola Virus

by Idrissa Diallo, Jeffrey Ho, Benoit Laffont, Jonathan Laugier, Abderrahim Benmoussa, Marine Lambert, Zeinab Husseini, Geoff Soule, Robert Kozak, Gary P. Kobinger and Patrick Provost

Int. J. Mol. Sci. 2021, 22(7), 3792; https://doi.org/10.3390/ijms22073792 - 06 Apr 2021

Cited by 11 | Viewed by 3571

Abstract

Ebola virus (EBOV) is a virulent pathogen, notorious for inducing life-threatening hemorrhagic fever, that has been responsible for several outbreaks in Africa and remains a public health threat. Yet, its pathogenesis is still not completely understood. Although there have been numerous studies on [...] Read more.

Ebola virus (EBOV) is a virulent pathogen, notorious for inducing life-threatening hemorrhagic fever, that has been responsible for several outbreaks in Africa and remains a public health threat. Yet, its pathogenesis is still not completely understood. Although there have been numerous studies on host transcriptional response to EBOV, with an emphasis on the clinical features, the impact of EBOV infection on post-transcriptional regulatory elements, such as microRNAs (miRNAs), remains largely unexplored. MiRNAs are involved in inflammation and immunity and are believed to be important modulators of the host response to viral infection. Here, we have used small RNA sequencing (sRNA-Seq), qPCR and functional analyses to obtain the first comparative miRNA transcriptome (miRNome) of a human liver cell line (Huh7) infected with one of the following three EBOV strains: Mayinga (responsible for the first Zaire outbreak in 1976), Makona (responsible for the West Africa outbreak in 2013–2016) and the epizootic Reston (presumably innocuous to humans). Our results highlight specific miRNA-based immunity pathways and substantial differences between the strains beyond their clinical manifestation and pathogenicity. These analyses shed new light into the molecular signature of liver cells upon EBOV infection and reveal new insights into miRNA-based virus attack and host defense strategy. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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15 pages, 2797 KiB

Open AccessArticle

Newly Isolated Animal Pathogen Corynebacterium silvaticum Is Cytotoxic to Human Epithelial Cells

by Jens Möller, Anne Busch, Christian Berens, Helmut Hotzel and Andreas Burkovski

Int. J. Mol. Sci. 2021, 22(7), 3549; https://doi.org/10.3390/ijms22073549 - 29 Mar 2021

Cited by 10 | Viewed by 2926

Abstract

Corynebacterium silvaticum is a newly identified animal pathogen of forest animals such as roe deer and wild boars. The species is closely related to the emerging human pathogen Corynebacterium ulcerans and the widely distributed animal pathogen Corynebacterium pseudotuberculosis. In this study, Corynebacterium [...] Read more.

Corynebacterium silvaticum is a newly identified animal pathogen of forest animals such as roe deer and wild boars. The species is closely related to the emerging human pathogen Corynebacterium ulcerans and the widely distributed animal pathogen Corynebacterium pseudotuberculosis. In this study, Corynebacterium silvaticum strain W25 was characterized with respect to its interaction with human cell lines. Microscopy, measurement of transepithelial electric resistance and cytotoxicity assays revealed detrimental effects of C. silvaticum to different human epithelial cell lines and to an invertebrate animal model, Galleria mellonella larvae, comparable to diphtheria toxin-secreting C. ulcerans. Furthermore, the results obtained may indicate a considerable zoonotic potential of this newly identified species. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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15 pages, 3882 KiB

Open AccessArticle

A Genomic Blueprint of Flax Fungal Parasite Fusarium oxysporum f. sp. lini

by Anastasia Samsonova, Alexander Kanapin, Michael Bankin, Anton Logachev, Maria Gretsova, Tatyana Rozhmina and Maria Samsonova

Int. J. Mol. Sci. 2021, 22(5), 2665; https://doi.org/10.3390/ijms22052665 - 06 Mar 2021

Cited by 6 | Viewed by 2381

Abstract

Fusarium wilt of flax is an aggressive disease caused by the soil-borne fungal pathogen Fusarium oxysporum f. sp. lini. It is a challenging pathogen presenting a constant threat to flax production industry worldwide. Previously, we reported chromosome-level assemblies of 5 highly pathogenic [...] Read more.

Fusarium wilt of flax is an aggressive disease caused by the soil-borne fungal pathogen Fusarium oxysporum f. sp. lini. It is a challenging pathogen presenting a constant threat to flax production industry worldwide. Previously, we reported chromosome-level assemblies of 5 highly pathogenic F. oxysporum f. sp. lini strains. We sought to characterize the genomic architecture of the fungus and outline evolutionary mechanisms shaping the pathogen genome. Here, we reveal the complex multi-compartmentalized genome organization and uncover its diverse evolutionary dynamics, which boosts genetic diversity and facilitates host adaptation. In addition, our results suggest that host of functions implicated in the life cycle of mobile genetic elements are main contributors to dissimilarity between proteomes of different Fusaria. Finally, our experiments demonstrate that mobile genetics elements are expressed in planta upon infection, alluding to their role in pathogenicity. On the whole, these results pave the way for further in-depth studies of evolutionary forces shaping the host–pathogen interaction. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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23 pages, 32800 KiB

Open AccessArticle

Comparative Genomics: Insights on the Pathogenicity and Lifestyle of Rhizoctonia solani

by Nurhani Mat Razali, Siti Norvahida Hisham, Ilakiya Sharanee Kumar, Rohit Nandan Shukla, Melvin Lee, Mohd Faizal Abu Bakar and Kalaivani Nadarajah

Int. J. Mol. Sci. 2021, 22(4), 2183; https://doi.org/10.3390/ijms22042183 - 22 Feb 2021

Cited by 11 | Viewed by 3218

Abstract

Proper management of agricultural disease is important to ensure sustainable food security. Staple food crops like rice, wheat, cereals, and other cash crops hold great export value for countries. Ensuring proper supply is critical; hence any biotic or abiotic factors contributing to the [...] Read more.

Proper management of agricultural disease is important to ensure sustainable food security. Staple food crops like rice, wheat, cereals, and other cash crops hold great export value for countries. Ensuring proper supply is critical; hence any biotic or abiotic factors contributing to the shortfall in yield of these crops should be alleviated. Rhizoctonia solani is a major biotic factor that results in yield losses in many agriculturally important crops. This paper focuses on genome informatics of our Malaysian Draft R. solani AG1-IA, and the comparative genomics (inter- and intra- AG) with four AGs including China AG1-IA (AG1-IA_KB317705.1), AG1-IB, AG3, and AG8. The genomic content of repeat elements, transposable elements (TEs), syntenic genomic blocks, functions of protein-coding genes as well as core orthologous genic information that underlies R. solani’s pathogenicity strategy were investigated. Our analyses show that all studied AGs have low content and varying profiles of TEs. All AGs were dominant for Class I TE, much like other basidiomycete pathogens. All AGs demonstrate dominance in Glycoside Hydrolase protein-coding gene assignments suggesting its importance in infiltration and infection of host. Our profiling also provides a basis for further investigation on lack of correlation observed between number of pathogenicity and enzyme-related genes with host range. Despite being grouped within the same AG with China AG1-IA, our Draft AG1-IA exhibits differences in terms of protein-coding gene proportions and classifications. This implies that strains from similar AG do not necessarily have to retain similar proportions and classification of TE but must have the necessary arsenal to enable successful infiltration and colonization of host. In a larger perspective, all the studied AGs essentially share core genes that are generally involved in adhesion, penetration, and host colonization. However, the different infiltration strategies will depend on the level of host resilience where this is clearly exhibited by the gene sets encoded for the process of infiltration, infection, and protection from host. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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23 pages, 4037 KiB

Open AccessArticle

Immune-Mediated Aggravation of the Campylobacter concisus-Induced Epithelial Barrier Dysfunction

by Praveen Kumar Nattramilarasu, Fábia Daniela Lobo de Sá, Jörg-Dieter Schulzke and Roland Bücker

Int. J. Mol. Sci. 2021, 22(4), 2043; https://doi.org/10.3390/ijms22042043 - 19 Feb 2021

Cited by 5 | Viewed by 2627

Abstract

Campylobacter concisus is a human-pathogenic bacterium of the gastrointestinal tract. This study aimed at the contribution of the mucosal immune system in the context of intestinal epithelial barrier dysfunction induced by C. concisus. As an experimental leaky gut model, we used in [...] Read more.

Campylobacter concisus is a human-pathogenic bacterium of the gastrointestinal tract. This study aimed at the contribution of the mucosal immune system in the context of intestinal epithelial barrier dysfunction induced by C. concisus. As an experimental leaky gut model, we used in vitro co-cultures of colonic epithelial cell monolayers (HT-29/B6-GR/MR) with M1-macrophage-like THP-1 cells on the basal side. Forty-eight hours after C. concisus infection, the decrease in the transepithelial electrical resistance in cell monolayers was more pronounced in co-culture condition and 22 ± 2% (p < 0.001) higher than the monoculture condition without THP-1 cells. Concomitantly, we observed a reduction in the expression of the tight junction proteins occludin and tricellulin. We also detected a profound increase in 4 kDa FITC-dextran permeability in C. concisus-infected cell monolayers only in co-culture conditions. This is explained by loss of tricellulin from tricellular tight junctions (tTJs) after C. concisus infection. As an underlying mechanism, we observed an inflammatory response after C. concisus infection through pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) released from THP-1 cells in the co-culture condition. In conclusion, the activation of subepithelial immune cells exacerbates colonic epithelial barrier dysfunction by C. concisus through tricellulin disruption in tTJs, leading to increased antigen permeability (leaky gut concept). Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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15 pages, 2105 KiB

Open AccessArticle

Two 20-Residue-Long Peptides Derived from Plasmodium vivax Merozoite Surface Protein 10 EGF-Like Domains Are Involved in Binding to Human Reticulocytes

by Laura Alejandra Ricaurte-Contreras, Andrea Lovera, Darwin Andrés Moreno-Pérez, Michel David Bohórquez, Carlos Fernando Suárez, Elizabeth Gutiérrez-Vásquez, Laura Cuy-Chaparro, Diego Garzón-Ospina and Manuel Alfonso Patarroyo

Int. J. Mol. Sci. 2021, 22(4), 1609; https://doi.org/10.3390/ijms22041609 - 05 Feb 2021

Cited by 2 | Viewed by 2461

Abstract

Plasmodium parasites’ invasion of their target cells is a complex, multi-step process involving many protein-protein interactions. Little is known about how complex the interaction with target cells is in Plasmodium vivax and few surface molecules related to reticulocytes’ adhesion have been described to [...] Read more.

Plasmodium parasites’ invasion of their target cells is a complex, multi-step process involving many protein-protein interactions. Little is known about how complex the interaction with target cells is in Plasmodium vivax and few surface molecules related to reticulocytes’ adhesion have been described to date. Natural selection, functional and structural analysis were carried out on the previously described vaccine candidate P. vivax merozoite surface protein 10 (PvMSP10) for evaluating its role during initial contact with target cells. It has been shown here that the recombinant carboxyl terminal region (rPvMSP10-C) bound to adult human reticulocytes but not to normocytes, as validated by two different protein-cell interaction assays. Particularly interesting was the fact that two 20-residue-long regions (³⁸⁸DKEECRCRANYMPDDSVDYF⁴⁰⁷ and ⁴¹⁵KDCSKENGNCDVNAECSIDK⁴³⁴) were able to inhibit rPvMSP10-C binding to reticulocytes and rosette formation using enriched target cells. These peptides were derived from PvMSP10 epidermal growth factor (EGF)-like domains (precisely, from a well-defined electrostatic zone) and consisted of regions having the potential of being B- or T-cell epitopes. These findings provide evidence, for the first time, about the fragments governing PvMSP10 binding to its target cells, thus highlighting the importance of studying them for inclusion in a P. vivax antimalarial vaccine. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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19 pages, 7343 KiB

Open AccessArticle

Characterization of Pathogenicity-Associated V2 Protein of Tobacco Curly Shoot Virus

by Mingjun Li, Changchang Li, Kairong Jiang, Ke Li, Junlei Zhang, Miao Sun, Gentu Wu and Ling Qing

Int. J. Mol. Sci. 2021, 22(2), 923; https://doi.org/10.3390/ijms22020923 - 18 Jan 2021

Cited by 9 | Viewed by 2204

Abstract

V2 proteins encoded by some whitefly-transmitted geminiviruses were reported to be functionally important proteins. However, the functions of the V2 protein of tobacco curly shoot virus (TbCSV), a monopartite begomovirus that causes leaf curl disease on tomato and tobacco in China, remains to [...] Read more.

V2 proteins encoded by some whitefly-transmitted geminiviruses were reported to be functionally important proteins. However, the functions of the V2 protein of tobacco curly shoot virus (TbCSV), a monopartite begomovirus that causes leaf curl disease on tomato and tobacco in China, remains to be characterized. In our report, an Agrobacterium infiltration-mediated transient expression assay indicated that TbCSV V2 can suppress local and systemic RNA silencing and the deletion analyses demonstrated that the amino acid region 1–92 of V2, including the five predicted α-helices, are required for local RNA silencing suppression. Site-directed substitutions showed that the conserved basic and ring-structured amino acids in TbCSV V2 are critical for its suppressor activity. Potato virus X-mediated heteroexpression of TbCSV V2 in Nicotiana benthamiana induced hypersensitive response-like (HR-like) cell death and systemic necrosis in a manner independent of V2′s suppressor activity. Furthermore, TbCSV infectious clone mutant with untranslated V2 protein (TbCSV_∆V2) could not induce visual symptoms, and coinfection with betasatellite (TbCSB) could obviously elevate the viral accumulation and symptom development. Interestingly, symptom recovery occurred at 15 days postinoculation (dpi) and onward in TbCSV_∆V2/TbCSB-inoculated plants. The presented work contributes to understanding the RNA silencing suppression activity of TbCSV V2 and extends our knowledge of the multifunctional role of begomovirus-encoded V2 proteins during viral infections. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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18 pages, 1259 KiB

Open AccessArticle

Virus–Host Protein–Protein Interactions between Human Papillomavirus 16 E6 A1 and D2/D3 Sub-Lineages: Variances and Similarities

by Guillem Dayer, Mehran L. Masoom, Melissa Togtema and Ingeborg Zehbe

Int. J. Mol. Sci. 2020, 21(21), 7980; https://doi.org/10.3390/ijms21217980 - 27 Oct 2020

Cited by 3 | Viewed by 5368

Abstract

High-risk strains of human papillomavirus are causative agents for cervical and other mucosal cancers, with type 16 being the most frequent. Compared to the European Prototype (EP; A1), the Asian-American (AA; D2/D3) sub-lineage seems to have increased abilities to promote carcinogenesis. Here, we [...] Read more.

High-risk strains of human papillomavirus are causative agents for cervical and other mucosal cancers, with type 16 being the most frequent. Compared to the European Prototype (EP; A1), the Asian-American (AA; D2/D3) sub-lineage seems to have increased abilities to promote carcinogenesis. Here, we studied protein–protein interactions (PPIs) between host proteins and sub-lineages of the key transforming E6 protein. We transduced human keratinocyte with EP or AA E6 genes and co-immunoprecipitated E6 proteins along with interacting cellular proteins to detect virus–host binding partners. AAE6 and EPE6 may have unique PPIs with host cellular proteins, conferring gain or loss of function and resulting in varied abilities to promote carcinogenesis. Using liquid chromatography-mass spectrometry and stringent interactor selection criteria based on the number of peptides, we identified 25 candidates: 6 unique to AAE6 and EPE6, along with 13 E6 targets common to both. A novel approach based on pathway selection discovered 171 target proteins: 90 unique AAE6 and 61 unique EPE6 along with 20 common E6 targets. Interpretations were made using databases, such as UniProt, BioGRID, and Reactome. Detected E6 targets were differentially implicated in important hallmarks of cancer: deregulating Notch signaling, energetics and hypoxia, DNA replication and repair, and immune response. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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21 pages, 4162 KiB

Open AccessArticle

Proteome Analysis of Walnut Bacterial Blight Disease

by Cíntia H. D. Sagawa, Renata de A. B. Assis, Paulo A. Zaini, Phillip A. Wilmarth, Brett S. Phinney, Leandro M. Moreira and Abhaya M. Dandekar

Int. J. Mol. Sci. 2020, 21(20), 7453; https://doi.org/10.3390/ijms21207453 - 09 Oct 2020

Cited by 11 | Viewed by 3696

Abstract

The interaction between the plant host, walnut (Juglans regia; Jr), and a deadly pathogen (Xanthomonas arboricola pv. juglandis 417; Xaj) can lead to walnut bacterial blight (WB), which depletes walnut productivity by degrading the nut quality. Here, we dissect this [...] Read more.

The interaction between the plant host, walnut (Juglans regia; Jr), and a deadly pathogen (Xanthomonas arboricola pv. juglandis 417; Xaj) can lead to walnut bacterial blight (WB), which depletes walnut productivity by degrading the nut quality. Here, we dissect this pathosystem using tandem mass tag quantitative proteomics. Walnut hull tissues inoculated with Xaj were compared to mock-inoculated tissues, and 3972 proteins were identified, of which 3296 are from Jr and 676 from Xaj. Proteins with differential abundance include oxidoreductases, proteases, and enzymes involved in energy metabolism and amino acid interconversion pathways. Defense responses and plant hormone biosynthesis were also increased. Xaj proteins detected in infected tissues demonstrate its ability to adapt to the host microenvironment, limiting iron availability, coping with copper toxicity, and maintaining energy and intermediary metabolism. Secreted proteases and extracellular secretion apparatus such as type IV pilus for twitching motility and type III secretion effectors indicate putative factors recognized by the host. Taken together, these results suggest intense degradation processes, oxidative stress, and general arrest of the biosynthetic metabolism in infected nuts. Our results provide insights into molecular mechanisms and highlight potential molecular tools for early detection and disease control strategies. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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25 pages, 10792 KiB

Open AccessArticle

Fatty Acid Synthase Beta Dehydratase in the Lipid Biosynthesis Pathway Is Required for Conidiogenesis, Pigmentation and Appressorium Formation in Magnaporthe oryzae S6

by Vaanee Sangappillai and Kalaivani Nadarajah

Int. J. Mol. Sci. 2020, 21(19), 7224; https://doi.org/10.3390/ijms21197224 - 30 Sep 2020

Cited by 15 | Viewed by 3676

Abstract

Lipid biosynthesis produces glycerol, which is important in fueling turgor pressure necessary for germination and penetration of plant host by fungi. As the relationship between pathogenicity and the lipid biosynthetic pathway is not fully understood, we have elucidated the role of the fatty [...] Read more.

Lipid biosynthesis produces glycerol, which is important in fueling turgor pressure necessary for germination and penetration of plant host by fungi. As the relationship between pathogenicity and the lipid biosynthetic pathway is not fully understood, we have elucidated the role of the fatty acid synthase beta subunit dehydratase (FAS1) gene in lipid biosynthesis. The FAS1 gene was silenced through homologous double crossover in Magnaporthe oryzae strain S6 to study the effect on lipid biosynthesis. The vegetative growth of Δfas1 mutants show the highest drop on oleic acid (between 10 and 50%), while the mycelial dry weight of mutants dropped significantly on all media. Conidiation of FAS1 mutants show a ~10- and ~5-fold reduction on oatmeal and Potato Dextrose Agar (PDA), respectively. Mutants formed mycelium that were mildly pigmented, indicating that the deletion of FAS1 may have affected melanin biosynthesis. Biochemical and gene expression studies concluded that the fatty acid degradation pathway might have been interrupted by FAS1 deletion. FAS1 mutants showed no enzyme activity on glucose or olive oil, suggesting that the mutants may lack functional peroxisomes and be defective in β-oxidation of fatty acids, hence explaining the reduced lipid deposits in the spores. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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12 pages, 1979 KiB

Open AccessArticle

Activation of Mechanistic Target of Rapamycin (mTOR) in Human Endothelial Cells Infected with Pathogenic Spotted Fever Group Rickettsiae

by Abha Sahni, Hema P. Narra and Sanjeev K. Sahni

Int. J. Mol. Sci. 2020, 21(19), 7179; https://doi.org/10.3390/ijms21197179 - 29 Sep 2020

Cited by 7 | Viewed by 2312

Abstract

Attributed to the tropism for host microvascular endothelium lining the blood vessels, vascular inflammation and dysfunction represent salient features of rickettsial pathogenesis, yet the details of fundamentally important pathogen interactions with host endothelial cells (ECs) as the primary targets of infection remain poorly [...] Read more.

Attributed to the tropism for host microvascular endothelium lining the blood vessels, vascular inflammation and dysfunction represent salient features of rickettsial pathogenesis, yet the details of fundamentally important pathogen interactions with host endothelial cells (ECs) as the primary targets of infection remain poorly appreciated. Mechanistic target of rapamycin (mTOR), a serine/threonine protein kinase of the phosphatidylinositol kinase-related kinase family, assembles into two functionally distinct complexes, namely mTORC1 (Raptor) and mTORC2 (Rictor), implicated in the determination of innate immune responses to intracellular pathogens via transcriptional regulation. In the present study, we investigated activation status of mTOR and its potential contributions to host EC responses during Rickettsia rickettsii and R. conorii infection. Protein lysates from infected ECs were analyzed for threonine 421/serine 424 phosphorylation of p70 S6 kinase (p70 S6K) and that of serine 2448 on mTOR itself as established markers of mTORC1 activation. For mTORC2, we assessed phosphorylation of protein kinase B (PKB or Akt) and protein kinase C (PKC), respectively, on serine 473 and serine 657. The results suggest increased phosphorylation of p70 S6K and mTOR during Rickettsia infection of ECs as early as 3 h and persisting for up to 24 h post-infection. The steady-state levels of phospho-Akt and phospho-PKC were also increased. Infection with pathogenic rickettsiae also resulted in the formation of microtubule-associated protein 1A/1B-light chain 3 (LC3-II) puncta and increased lipidation of LC3-II, a response significantly inhibited by introduction of siRNA targeting mTORC1 into ECs. These findings thus yield first evidence for the activation of both mTORC1 and mTORC2 during EC infection in vitro with Rickettsia species and suggest that early induction of autophagy in response to intracellular infection might be regulated by this important pathway known to function as a central integrator of cellular immunity and inflammation. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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20 pages, 3086 KiB

Open AccessArticle

Xylella fastidiosa subsp. pauca Strains Fb7 and 9a5c from Citrus Display Differential Behavior, Secretome, and Plant Virulence

by Jessica Brito de Souza, Hebréia Oliveira Almeida-Souza, Paulo Adriano Zaini, Mônica Neli Alves, Aline Gomes de Souza, Paulo Marques Pierry, Aline Maria da Silva, Luiz Ricardo Goulart, Abhaya M. Dandekar and Rafael Nascimento

Int. J. Mol. Sci. 2020, 21(18), 6769; https://doi.org/10.3390/ijms21186769 - 15 Sep 2020

Cited by 8 | Viewed by 3829

Abstract

Xylella fastidiosa colonizes the xylem of various cultivated and native plants worldwide. Citrus production in Brazil has been seriously affected, and major commercial varieties remain susceptible to Citrus Variegated Chlorosis (CVC). Collective cellular behaviors such as biofilm formation influence virulence and insect transmission [...] Read more.

Xylella fastidiosa colonizes the xylem of various cultivated and native plants worldwide. Citrus production in Brazil has been seriously affected, and major commercial varieties remain susceptible to Citrus Variegated Chlorosis (CVC). Collective cellular behaviors such as biofilm formation influence virulence and insect transmission of X. fastidiosa. The reference strain 9a5c produces a robust biofilm compared to Fb7 that remains mostly planktonic, and both were isolated from symptomatic citrus trees. This work deepens our understanding of these distinct behaviors at the molecular level, by comparing the cellular and secreted proteomes of these two CVC strains. Out of 1017 identified proteins, 128 showed differential abundance between the two strains. Different protein families were represented such as proteases, hemolysin-like proteins, and lipase/esterases, among others. Here we show that the lipase/esterase LesA is among the most abundant secreted proteins of CVC strains as well, and demonstrate its functionality by complementary activity assays. More severe symptoms were observed in Nicotiana tabacum inoculated with strain Fb7 compared to 9a5c. Our results support that systemic symptom development can be accelerated by strains that invest less in biofilm formation and more in plant colonization. This has potential application in modulating the bacterial-plant interaction and reducing disease severity. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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21 pages, 5112 KiB

Open AccessArticle

IKKγ/NEMO Is Required to Confer Antimicrobial Innate Immune Responses in the Yellow Mealworm, Tenebrio Molitor

by Hye Jin Ko, Yong Hun Jo, Bharat Bhusan Patnaik, Ki Beom Park, Chang Eun Kim, Maryam Keshavarz, Ho Am Jang, Yong Seok Lee and Yeon Soo Han

Int. J. Mol. Sci. 2020, 21(18), 6734; https://doi.org/10.3390/ijms21186734 - 14 Sep 2020

Cited by 11 | Viewed by 2446

Abstract

IKKγ/NEMO is the regulatory subunit of the IκB kinase (IKK) complex, which regulates the NF-κB signaling pathway. Within the IKK complex, IKKγ/NEMO is the non-catalytic subunit, whereas IKKα and IKKβ are the structurally related catalytic subunits. In [...] Read more.

IKKγ/NEMO is the regulatory subunit of the IκB kinase (IKK) complex, which regulates the NF-κB signaling pathway. Within the IKK complex, IKKγ/NEMO is the non-catalytic subunit, whereas IKKα and IKKβ are the structurally related catalytic subunits. In this study, TmIKKγ was screened from the Tenebrio molitor RNA-Seq database and functionally characterized using RNAi screening for its role in regulating T. molitor antimicrobial peptide (AMP) genes after microbial challenges. The TmIKKγ transcript is 1521 bp that putatively encodes a polypeptide of 506 amino acid residues. TmIKKγ contains a NF-κB essential modulator (NEMO) and a leucine zipper domain of coiled coil region 2 (LZCC2). A phylogenetic analysis confirmed its homology to the red flour beetle, Tribolium castaneum IKKγ (TcIKKγ). The expression of TmIKKγ mRNA showed that it might function in diverse tissues of the insect, with a higher expression in the hemocytes and the fat body of the late-instar larvae. TmIKKγ mRNA expression was induced by Escherichia coli, Staphylococcus aureus, and Candida albicans challenges in the whole larvae and in tissues such as the hemocytes, gut and fat body. The knockdown of TmIKKγ mRNA significantly reduced the survival of the larvae after microbial challenges. Furthermore, we investigated the tissue-specific induction patterns of fourteen T. molitor AMP genes in TmIKKγ mRNA-silenced individuals after microbial challenges. In general, the mRNA expression of TmTenecin1, -2, and -4; TmDefensin1 and -2; TmColeoptericin1 and 2; and TmAttacin1a, 1b, and 2 were found to be downregulated in the hemocytes, gut, and fat body tissues in the TmIKKγ-silenced individuals after microbial challenges. Under similar conditions, TmRelish (NF-κB transcription factor) mRNA was also found to be downregulated. Thus, TmIKKγ is an important factor in the antimicrobial innate immune response of T. molitor. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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19 pages, 5601 KiB

Open AccessArticle

Biosurfactants Induce Antimicrobial Peptide Production through the Activation of TmSpatzles in Tenebrio molitor

by Tariku Tesfaye Edosa, Yong Hun Jo, Maryam Keshavarz, In Seon Kim and Yeon Soo Han

Int. J. Mol. Sci. 2020, 21(17), 6090; https://doi.org/10.3390/ijms21176090 - 24 Aug 2020

Cited by 7 | Viewed by 2268

Abstract

Biosurfactant immunomodulatory activities in mammals, nematodes, and plants have been investigated. However, the immune activation property of biosurfactants in insects has not been reported. Therefore, here, we studied the defense response triggered by lipopeptides (fengycin and iturin A), glycolipids (rhamnolipid), and cyclic polypeptides [...] Read more.

Biosurfactant immunomodulatory activities in mammals, nematodes, and plants have been investigated. However, the immune activation property of biosurfactants in insects has not been reported. Therefore, here, we studied the defense response triggered by lipopeptides (fengycin and iturin A), glycolipids (rhamnolipid), and cyclic polypeptides (bacitracin) in the coleopteran insect, mealworm Tenebrio molitor. The in vitro antimicrobial activities against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and fungi (Candida albicans) were assessed by mixing these pathogens with the hemolymph of biosurfactant-immune-activated larvae. E. coli growth was remarkably inhibited by this hemolymph. The antimicrobial peptide (AMP) induction results also revealed that all biosurfactants tested induced several AMPs, exclusively in hemocytes. The survivability analysis of T. molitor larvae challenged by E. coli (10⁶ CFU/µL) at 24 h post biosurfactant-immune activation showed that fengycin, iturin A, and rhamnopid significantly increased survivability against E. coli. Biosurfactant-induced TmSpatzles activation was also monitored, and the results showed that TmSpz3 and TmSpz-like were upregulated in the hemocytes of iturin A-injected larvae, while TmSpz4 and TmSpz6 were upregulated in the fat bodies of the fengycin-, iturin A-, and rhamnolipid-injected larvae. Overall, these results suggest that lipopeptide and glycolipid biosurfactants induce the expression of AMPs in T. molitor via the activation of spätzle genes, thereby increasing the survivability of T. molitor against E. coli. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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23 pages, 3197 KiB

Open AccessArticle

Choline Supplementation Sensitizes Legionella dumoffii to Galleria mellonella Apolipophorin III

by Marta Palusińska-Szysz, Agnieszka Zdybicka-Barabas, Rafał Luchowski, Emilia Reszczyńska, Justyna Śmiałek, Paweł Mak, Wiesław I. Gruszecki and Małgorzata Cytryńska

Int. J. Mol. Sci. 2020, 21(16), 5818; https://doi.org/10.3390/ijms21165818 - 13 Aug 2020

Cited by 4 | Viewed by 2577

Abstract

The growth of Legionella dumoffii can be inhibited by Galleria mellonella apolipophorin III (apoLp-III) which is an insect homologue of human apolipoprotein E., and choline-cultured L. dumoffii cells are considerably more susceptible to apoLp-III than bacteria grown without choline supplementation. In the present [...] Read more.

The growth of Legionella dumoffii can be inhibited by Galleria mellonella apolipophorin III (apoLp-III) which is an insect homologue of human apolipoprotein E., and choline-cultured L. dumoffii cells are considerably more susceptible to apoLp-III than bacteria grown without choline supplementation. In the present study, the interactions of apoLp-III with intact L. dumoffii cells cultured without and with exogenous choline were analyzed to explain the basis of this difference. Fluorescently labeled apoLp-III (FITC-apoLp-III) bound more efficiently to choline-grown L. dumoffii, as revealed by laser scanning confocal microscopy. The cell envelope of these bacteria was penetrated more deeply by FITC-apoLp-III, as demonstrated by fluorescence lifetime imaging microscopy analyses. The increased susceptibility of the choline-cultured L. dumoffii to apoLp-III was also accompanied by alterations in the cell surface topography and nanomechanical properties. A detailed analysis of the interaction of apoLp-III with components of the L. dumoffii cells was carried out using both purified lipopolysaccharide (LPS) and liposomes composed of L. dumoffii phospholipids and LPS. A single micelle of L. dumoffii LPS was formed from 12 to 29 monomeric LPS molecules and one L. dumoffii LPS micelle bound two molecules of apoLp-III. ApoLp-III exhibited the strongest interactions with liposomes with incorporated LPS formed of phospholipids isolated from bacteria cultured on exogenous choline. These results indicated that the differences in the phospholipid content in the cell membrane, especially PC, and LPS affected the interactions of apoLp-III with bacterial cells and suggested that these differences contributed to the increased susceptibility of the choline-cultured L. dumoffii to G. mellonella apoLp-III. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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21 pages, 5490 KiB

Open AccessArticle

Role of Bacterial and Host DNases on Host-Pathogen Interaction during Streptococcus suis Meningitis

by Marita Meurer, Sophie Öhlmann, Marta C. Bonilla, Peter Valentin-Weigand, Andreas Beineke, Isabel Hennig-Pauka, Christian Schwerk, Horst Schroten, Christoph G. Baums, Maren von Köckritz-Blickwede and Nicole de Buhr

Int. J. Mol. Sci. 2020, 21(15), 5289; https://doi.org/10.3390/ijms21155289 - 25 Jul 2020

Cited by 20 | Viewed by 2685

Abstract

Streptococcus suis is a zoonotic agent causing meningitis in pigs and humans. Neutrophils, as the first line of defense against S. suis infections, release neutrophil extracellular traps (NETs) to entrap pathogens. In this study, we investigated the role of the secreted nuclease A [...] Read more.

Streptococcus suis is a zoonotic agent causing meningitis in pigs and humans. Neutrophils, as the first line of defense against S. suis infections, release neutrophil extracellular traps (NETs) to entrap pathogens. In this study, we investigated the role of the secreted nuclease A of S. suis (SsnA) as a NET-evasion factor in vivo and in vitro. Piglets were intranasally infected with S. suis strain 10 or an isogenic ssnA mutant. DNase and NET-formation were analyzed in cerebrospinal fluid (CSF) and brain tissue. Animals infected with S. suis strain 10 or S. suis 10ΔssnA showed the presence of NETs in CSF and developed similar clinical signs. Therefore, SsnA does not seem to be a crucial virulence factor that contributes to the development of meningitis in pigs. Importantly, DNase activity was detectable in the CSF of both infection groups, indicating that host nucleases, in contrast to bacterial nuclease SsnA, may play a major role during the onset of meningitis. The effect of DNase 1 on neutrophil functions was further analyzed in a 3D-cell culture model of the porcine blood–CSF barrier. We found that DNase 1 partially contributes to enhanced killing of S. suis by neutrophils, especially when plasma is present. In summary, host nucleases may partially contribute to efficient innate immune response in the CSF. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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18 pages, 3168 KiB

Open AccessArticle

Tubulin Folding Cofactor TBCB is a Target of the Salmonella Effector Protein SseK1

by Juan Luis Araujo-Garrido, Fernando Baisón-Olmo, Joaquín Bernal-Bayard, Francisco Romero and Francisco Ramos-Morales

Int. J. Mol. Sci. 2020, 21(9), 3193; https://doi.org/10.3390/ijms21093193 - 30 Apr 2020

Cited by 6 | Viewed by 2752

Abstract

Salmonella enterica serovar Typhimurium is a human and animal pathogen that uses type III secretion system effectors to manipulate the host cell and fulfill infection. SseK1 is a Salmonella effector with glycosyltransferase activity. We carried out a yeast two-hybrid screen and have identified [...] Read more.

Salmonella enterica serovar Typhimurium is a human and animal pathogen that uses type III secretion system effectors to manipulate the host cell and fulfill infection. SseK1 is a Salmonella effector with glycosyltransferase activity. We carried out a yeast two-hybrid screen and have identified tubulin-binding cofactor B (TBCB) as a new binding partner for this effector. SseK1 catalyzed the addition of N-acetylglucosamine to arginine on TBCB, and its expression promoted the stabilization of the microtubule cytoskeleton of HEK293T cells. The conserved Asp-x-Asp (DxD) motif that is essential for the activity of SseK1 was required for the binding and modification of TBCB and for the effect on the cytoskeleton. Our study has identified a novel target for SseK1 and suggests that this effector may have a role in the manipulation of the host cell microtubule network to provide a safe niche for this pathogen. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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16 pages, 3450 KiB

Open AccessArticle

Aedes albopictus Autophagy-Related Gene 8 (AaAtg8) Is Required to Confer Anti-Bacterial Gut Immunity

by Chang Eun Kim, Ki Beom Park, Hye Jin Ko, Maryam Keshavarz, Young Min Bae, BoBae Kim, Bharat Bhusan Patnaik, Ho Am Jang, Yong Seok Lee, Yeon Soo Han and Yong Hun Jo

Int. J. Mol. Sci. 2020, 21(8), 2944; https://doi.org/10.3390/ijms21082944 - 22 Apr 2020

Cited by 10 | Viewed by 2846

Abstract

Autophagy is an important process by which pathogens and damaged or unused organelles are eliminated. The role of autophagy in development and the immune response to pathogens is well established. Autophagy-related protein 8 (Atg8) is involved in the formation of the autophagosome and, [...] Read more.

Autophagy is an important process by which pathogens and damaged or unused organelles are eliminated. The role of autophagy in development and the immune response to pathogens is well established. Autophagy-related protein 8 (Atg8) is involved in the formation of the autophagosome and, with the help of the serine protease Atg4, mediates the delivery of both vesicles and the autophagosome to the vacuole. Here, we cloned the Aedes albopictus autophagy-related protein 8 (AaAtg8) gene and characterized its role in the innate immunity of the mosquito against microbial infections. AaAtg8 is comprised of an open reading frame (ORF) region of 357 bp encoding a polypeptide of 118 amino acid residues. A domain analysis of AaAtg8 revealed an Atg8 ubiquitin-like domain, Atg7/Atg4 interaction sites, and peptide binding sites. The AaAtg8 mRNA expression was high in the Malpighian tubules and heads of both sugar-fed and blood-fed adult female mosquitoes. The expression level of AaAtg8 mRNA increased in the midgut and abdominal carcass following being challenged with Listeria monocytogenes. To investigate the role of AaAtg8 in the innate immune responses of Ae. albopictus, AaAtg8 gene-silenced adult mosquitoes were challenged by injection or by being fed microorganisms in blood. High mortality rates were observed in mosquitoes in which AaAtg8 was silenced after challenges of microorganisms to the host by blood feeding. This suggests that Atg8-autophagy plays a critical role in the gut immunity in Ae. albopictus. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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12 pages, 835 KiB

Open AccessArticle

Construction of a Lectin–Glycan Interaction Network from Enterohemorrhagic Escherichia coli Strains by Multi-omics Analysis

by Seung-Hak Cho, Kang Mo Lee, Cheorl-Ho Kim and Sung Soon Kim

Int. J. Mol. Sci. 2020, 21(8), 2681; https://doi.org/10.3390/ijms21082681 - 12 Apr 2020

Cited by 8 | Viewed by 2559

Abstract

Enterohemorrhagic Escherichia coli (EHEC) causes hemorrhagic colitis and hemolytic uremic syndrome. EHEC infection begins with bacterial adherence to the host intestine via lectin-like adhesins that bind to the intestinal wall. However, EHEC-related lectin–glycan interactions (LGIs) remain unknown. Here, we conducted a genome-wide investigation [...] Read more.

Enterohemorrhagic Escherichia coli (EHEC) causes hemorrhagic colitis and hemolytic uremic syndrome. EHEC infection begins with bacterial adherence to the host intestine via lectin-like adhesins that bind to the intestinal wall. However, EHEC-related lectin–glycan interactions (LGIs) remain unknown. Here, we conducted a genome-wide investigation of putative adhesins to construct an LGI network. We performed microarray-based transcriptomic and proteomic analyses with E. coli EDL933. Using PSORTb-based analysis, potential outer-membrane-embedded adhesins were predicted from the annotated genes of 318 strains. Predicted proteins were classified using TMHMM v2.0, SignalP v5.0, and LipoP v1.0. Functional and protein–protein interaction analyses were performed using InterProScan and String databases, respectively. Structural information of lectin candidate proteins was predicted using Iterative Threading ASSEmbly Refinement (I-TASSER) and Spatial Epitope Prediction of Protein Antigens (SEPPA) tools based on 3D structure and B-cell epitopes. Pathway analysis returned 42,227 Gene Ontology terms; we then selected 2585 lectin candidate proteins by multi-omics analysis and performed homology modeling and B-cell epitope analysis. We predicted a total of 24,400 outer-membrane-embedded proteins from the genome of 318 strains and integrated multi-omics information into the genomic information of the proteins. Our integrated multi-omics data will provide a useful resource for the construction of LGI networks of E. coli. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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17 pages, 969 KiB

Open AccessReview

The Role of Lipids in Legionella-Host Interaction

by Bozena Kowalczyk, Elzbieta Chmiel and Marta Palusinska-Szysz

Int. J. Mol. Sci. 2021, 22(3), 1487; https://doi.org/10.3390/ijms22031487 - 02 Feb 2021

Cited by 9 | Viewed by 3667

Abstract

Legionella are Gram-stain-negative rods associated with water environments: either natural or man-made systems. The inhalation of aerosols containing Legionella bacteria leads to the development of a severe pneumonia termed Legionnaires’ disease. To establish an infection, these bacteria adapt to growth in the hostile [...] Read more.

Legionella are Gram-stain-negative rods associated with water environments: either natural or man-made systems. The inhalation of aerosols containing Legionella bacteria leads to the development of a severe pneumonia termed Legionnaires’ disease. To establish an infection, these bacteria adapt to growth in the hostile environment of the host through the unusual structures of macromolecules that build the cell surface. The outer membrane of the cell envelope is a lipid bilayer with an asymmetric composition mostly of phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet. The major membrane-forming phospholipid of Legionella spp. is phosphatidylcholine (PC)—a typical eukaryotic glycerophospholipid. PC synthesis in Legionella cells occurs via two independent pathways: the N-methylation (Pmt) pathway and the Pcs pathway. The utilisation of exogenous choline by Legionella spp. leads to changes in the composition of lipids and proteins, which influences the physicochemical properties of the cell surface. This phenotypic plasticity of the Legionella cell envelope determines the mode of interaction with the macrophages, which results in a decrease in the production of proinflammatory cytokines and modulates the interaction with antimicrobial peptides and proteins. The surface-exposed O-chain of Legionella pneumophila sg1 LPS consisting of a homopolymer of 5-acetamidino-7-acetamido-8-O-acetyl-3,5,7,9-tetradeoxy-l-glycero-d-galacto-non-2-ulosonic acid is probably the first component in contact with the host cell that anchors the bacteria in the host membrane. Unusual in terms of the structure and function of individual LPS regions, it makes an important contribution to the antigenicity and pathogenicity of Legionella bacteria. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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23 pages, 1736 KiB

Open AccessReview

Insights into the Role of Tick Salivary Protease Inhibitors during Ectoparasite–Host Crosstalk

by Mohamed Amine Jmel, Hajer Aounallah, Chaima Bensaoud, Imen Mekki, Jindřich Chmelař, Fernanda Faria, Youmna M’ghirbi and Michalis Kotsyfakis

Int. J. Mol. Sci. 2021, 22(2), 892; https://doi.org/10.3390/ijms22020892 - 17 Jan 2021

Cited by 13 | Viewed by 4398

Abstract

Protease inhibitors (PIs) are ubiquitous regulatory proteins present in all kingdoms. They play crucial tasks in controlling biological processes directed by proteases which, if not tightly regulated, can damage the host organism. PIs can be classified according to their targeted proteases or their [...] Read more.

Protease inhibitors (PIs) are ubiquitous regulatory proteins present in all kingdoms. They play crucial tasks in controlling biological processes directed by proteases which, if not tightly regulated, can damage the host organism. PIs can be classified according to their targeted proteases or their mechanism of action. The functions of many PIs have now been characterized and are showing clinical relevance for the treatment of human diseases such as arthritis, hepatitis, cancer, AIDS, and cardiovascular diseases, amongst others. Other PIs have potential use in agriculture as insecticides, anti-fungal, and antibacterial agents. PIs from tick salivary glands are special due to their pharmacological properties and their high specificity, selectivity, and affinity to their target proteases at the tick–host interface. In this review, we discuss the structure and function of PIs in general and those PI superfamilies abundant in tick salivary glands to illustrate their possible practical applications. In doing so, we describe tick salivary PIs that are showing promise as drug candidates, highlighting the most promising ones tested in vivo and which are now progressing to preclinical and clinical trials. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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18 pages, 1365 KiB

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Regulatory RNAs: A Universal Language for Inter-Domain Communication

by Emma Layton, Anna-Marie Fairhurst, Sam Griffiths-Jones, Richard K. Grencis and Ian S. Roberts

Int. J. Mol. Sci. 2020, 21(23), 8919; https://doi.org/10.3390/ijms21238919 - 24 Nov 2020

Cited by 17 | Viewed by 4588

Abstract

In eukaryotes, microRNAs (miRNAs) have roles in development, homeostasis, disease and the immune response. Recent work has shown that plant and mammalian miRNAs also mediate cross-kingdom and cross-domain communications. However, these studies remain controversial and are lacking critical mechanistic explanations. Bacteria do not [...] Read more.

In eukaryotes, microRNAs (miRNAs) have roles in development, homeostasis, disease and the immune response. Recent work has shown that plant and mammalian miRNAs also mediate cross-kingdom and cross-domain communications. However, these studies remain controversial and are lacking critical mechanistic explanations. Bacteria do not produce miRNAs themselves, and therefore it is unclear how these eukaryotic RNA molecules could function in the bacterial recipient. In this review, we compare and contrast the biogenesis and functions of regulatory RNAs in eukaryotes and bacteria. As a result, we discovered several conserved features and homologous components in these distinct pathways. These findings enabled us to propose novel mechanisms to explain how eukaryotic miRNAs could function in bacteria. Further understanding in this area is necessary to validate the findings of existing studies and could facilitate the use of miRNAs as novel tools for the directed remodelling of the human microbiota. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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24 pages, 5520 KiB

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Interactions and Signal Transduction Pathways Involved during Central Nervous System Entry by Neisseria meningitidis across the Blood–Brain Barriers

by Julia Borkowski, Horst Schroten and Christian Schwerk

Int. J. Mol. Sci. 2020, 21(22), 8788; https://doi.org/10.3390/ijms21228788 - 20 Nov 2020

Cited by 4 | Viewed by 3496

Abstract

The Gram-negative diplococcus Neisseria meningitidis, also called meningococcus, exclusively infects humans and can cause meningitis, a severe disease that can lead to the death of the afflicted individuals. To cause meningitis, the bacteria have to enter the central nervous system (CNS) by [...] Read more.

The Gram-negative diplococcus Neisseria meningitidis, also called meningococcus, exclusively infects humans and can cause meningitis, a severe disease that can lead to the death of the afflicted individuals. To cause meningitis, the bacteria have to enter the central nervous system (CNS) by crossing one of the barriers protecting the CNS from entry by pathogens. These barriers are represented by the blood–brain barrier separating the blood from the brain parenchyma and the blood–cerebrospinal fluid (CSF) barriers at the choroid plexus and the meninges. During the course of meningococcal disease resulting in meningitis, the bacteria undergo several interactions with host cells, including the pharyngeal epithelium and the cells constituting the barriers between the blood and the CSF. These interactions are required to initiate signal transduction pathways that are involved during the crossing of the meningococci into the blood stream and CNS entry, as well as in the host cell response to infection. In this review we summarize the interactions and pathways involved in these processes, whose understanding could help to better understand the pathogenesis of meningococcal meningitis. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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18 pages, 702 KiB

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Phytopathogenic Cercosporoid Fungi—From Taxonomy to Modern Biochemistry and Molecular Biology

by Urszula Świderska-Burek, Margaret E. Daub, Elizabeth Thomas, Magdalena Jaszek, Anna Pawlik and Grzegorz Janusz

Int. J. Mol. Sci. 2020, 21(22), 8555; https://doi.org/10.3390/ijms21228555 - 13 Nov 2020

Cited by 15 | Viewed by 4576

Abstract

Phytopathogenic cercosporoid fungi have been investigated comprehensively due to their important role in causing plant diseases. A significant amount of research has been focused on the biology, morphology, systematics, and taxonomy of this group, with less of a focus on molecular or biochemical [...] Read more.

Phytopathogenic cercosporoid fungi have been investigated comprehensively due to their important role in causing plant diseases. A significant amount of research has been focused on the biology, morphology, systematics, and taxonomy of this group, with less of a focus on molecular or biochemical issues. Early and extensive research on these fungi focused on taxonomy and their classification based on in vivo features. Lately, investigations have mainly addressed a combination of characteristics such as morphological traits, host specificity, and molecular analyses initiated at the end of the 20th century. Some species that are important from an economic point of view have been more intensively investigated by means of genetic and biochemical methods to better understand the pathogenesis processes. Cercosporin, a photoactivated toxin playing an important role in Cercospora diseases, has been extensively studied. Understanding cercosporin toxicity in relation to reactive oxygen species (ROS) production facilitated the discovery and regulation of the cercosporin biosynthesis pathway, including the gene cluster encoding pathway enzymes. Furthermore, these fungi may be a source of other biotechnologically important compounds, e.g., industrially relevant enzymes. This paper reviews methods and important results of investigations of this group of fungi addressed at different levels over the years. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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35 pages, 377 KiB

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Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

by Daniel M. Mrochen, Liliane M. Fernandes de Oliveira, Dina Raafat and Silva Holtfreter

Int. J. Mol. Sci. 2020, 21(19), 7061; https://doi.org/10.3390/ijms21197061 - 25 Sep 2020

Cited by 18 | Viewed by 4120

Abstract

Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus [...] Read more.

Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naïve laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S.aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

22 pages, 1363 KiB

Open AccessReview

Keeping in Touch with Type-III Secretion System Effectors: Mass Spectrometry-Based Proteomics to Study Effector–Host Protein–Protein Interactions

by Margaux De Meyer, Joren De Ryck, Sofie Goormachtig and Petra Van Damme

Int. J. Mol. Sci. 2020, 21(18), 6891; https://doi.org/10.3390/ijms21186891 - 19 Sep 2020

Cited by 4 | Viewed by 4483

Abstract

Manipulation of host cellular processes by translocated bacterial effectors is key to the success of bacterial pathogens and some symbionts. Therefore, a comprehensive understanding of effectors is of critical importance to understand infection biology. It has become increasingly clear that the identification of [...] Read more.

Manipulation of host cellular processes by translocated bacterial effectors is key to the success of bacterial pathogens and some symbionts. Therefore, a comprehensive understanding of effectors is of critical importance to understand infection biology. It has become increasingly clear that the identification of host protein targets contributes invaluable knowledge to the characterization of effector function during pathogenesis. Recent advances in mapping protein–protein interaction networks by means of mass spectrometry-based interactomics have enabled the identification of host targets at large-scale. In this review, we highlight mass spectrometry-driven proteomics strategies and recent advances to elucidate type-III secretion system effector–host protein–protein interactions. Furthermore, we highlight approaches for defining spatial and temporal effector–host interactions, and discuss possible avenues for studying natively delivered effectors in the context of infection. Overall, the knowledge gained when unravelling effector complexation with host factors will provide novel opportunities to control infectious disease outcomes. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 2.0)

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