Journal of Fungi

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7 pages, 2710 KiB

Open AccessArticle

Do Pentraxins Bind to Fungi in Invasive Human Gastrointestinal Candidiasis?

by Umamaheshwari Golconda, Richard E. Sobonya and Stephen A. Klotz

J. Fungi 2018, 4(3), 111; https://doi.org/10.3390/jof4030111 - 17 Sep 2018

Cited by 3 | Viewed by 2799

Abstract

Tissue from 13 autopsy cases with invasive gastrointestinal candidiasis was studied for the binding of the pentraxins, C-reactive protein (CRP), pentraxin 3 (PTX3), and serum amyloid P component (SAP) to fungal surfaces. Invasive candidal infection was demonstrated using a hematoxylin and eosin stain [...] Read more.

Tissue from 13 autopsy cases with invasive gastrointestinal candidiasis was studied for the binding of the pentraxins, C-reactive protein (CRP), pentraxin 3 (PTX3), and serum amyloid P component (SAP) to fungal surfaces. Invasive candidal infection was demonstrated using a hematoxylin and eosin stain and a Gomori methenamine silver stain (GMS). Immunohistochemistry was performed with CRP and PTX3 monoclonal antibodies and did not demonstrate CRP or PTX3 bound to fungi (0 of 13 cases), although CRP was extensively deposited on human tissue. A polyclonal antibody to SAP showed that SAP was bound to fungi in 12 of 13 cases. Although all three pentraxins have been reported to bind to fungi or bacteria, only SAP was bound to filamentous and yeast forms of Candida in human tissue, as detected by immunohistochemistry. SAP was abundantly present on fungi and may have affected the host innate immune response to the invading fungi. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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17 pages, 5634 KiB

Open AccessArticle

Impact of Fungal MAPK Pathway Targets on the Cell Wall

by Jacky Chow, Marysa Notaro, Aditi Prabhakar, Stephen J. Free and Paul J. Cullen

J. Fungi 2018, 4(3), 93; https://doi.org/10.3390/jof4030093 - 09 Aug 2018

Cited by 13 | Viewed by 4897

Abstract

The fungal cell wall is an extracellular organelle that provides structure and protection to cells. The cell wall also influences the interactions of cells with each other and surfaces. The cell wall can be reorganized in response to changing environmental conditions and different [...] Read more.

The fungal cell wall is an extracellular organelle that provides structure and protection to cells. The cell wall also influences the interactions of cells with each other and surfaces. The cell wall can be reorganized in response to changing environmental conditions and different types of stress. Signaling pathways control the remodeling of the cell wall through target proteins that are in many cases not well defined. The Mitogen Activated Protein Kinase pathway that controls filamentous growth in yeast (fMAPK) was required for normal growth in media containing the cell wall perturbing agent Calcofluor White (CFW). A mass spectrometry (MASS-SPEC) approach and analysis of expression profiling data identified cell wall proteins and modifying enzymes whose levels were influenced by the fMAPK pathway. These include Flo11p, Flo10p, Tip1p, Pry2p and the mannosyltransferase, Och1p. Cells lacking Flo11p or Och1p were sensitive to CFW. The identification of cell wall proteins controlled by a MAPK pathway may provide insights into how signaling pathways regulate the cell wall. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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18 pages, 5003 KiB

Open AccessArticle

Biological Roles of Protein-Coding Tandem Repeats in the Yeast Candida Albicans

by Matt Wilkins, Ningxin Zhang and Jan Schmid

J. Fungi 2018, 4(3), 78; https://doi.org/10.3390/jof4030078 - 29 Jun 2018

Cited by 10 | Viewed by 3775

Abstract

Tandem repeat (TR) DNA mutates faster than other DNA by insertion and deletion of repeats. Large parts of eukaryotic proteomes are encoded by ORFs containing protein-coding TRs (TR-ORFs, pcTRs) with largely unknown biological consequences. We explored these in the yeast Candida albicans, [...] Read more.

Tandem repeat (TR) DNA mutates faster than other DNA by insertion and deletion of repeats. Large parts of eukaryotic proteomes are encoded by ORFs containing protein-coding TRs (TR-ORFs, pcTRs) with largely unknown biological consequences. We explored these in the yeast Candida albicans, an opportunistic human pathogen. We found that almost half of C. albicans’ proteins are encoded by TR-ORFs. pcTR frequency differed only moderately between different gene (GO) categories. Bioinformatic predictions of genome-wide mutation rates and clade-specific differences in pcTR allele frequencies indicated that pcTRs (i) significantly increase the genome-wide mutation rate; (ii) significantly impact on fitness and (iii) allow the evolution of selectively advantageous clade-specific protein variants. Synonymous mutations reduced the repetitiveness of many amino acid repeat-encoding pcTRs. A survey, in 58 strains, revealed that in some pcTR regions in which repetitiveness was not significantly diminished by synonymous mutations the habitat predicted which alleles were present, suggesting roles of pcTR mutation in short-term adaptation and pathogenesis. In C. albicans pcTR mutation apparently is an important mechanism for mutational advance and possibly also rapid adaptation, with synonymous mutations providing a mechanism for adjusting mutation rates of individual pcTRs. Analyses of Arabidopsis and human pcTRs showed that the latter also occurs in other eukaryotes. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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12 pages, 3405 KiB

Open AccessArticle

An In Vitro Model for Candida albicans–Streptococcus gordonii Biofilms on Titanium Surfaces

by Daniel Montelongo-Jauregui, Anand Srinivasan, Anand K. Ramasubramanian and Jose L. Lopez-Ribot

J. Fungi 2018, 4(2), 66; https://doi.org/10.3390/jof4020066 - 04 Jun 2018

Cited by 33 | Viewed by 4707

Abstract

The oral cavity serves as a nutrient-rich haven for over 600 species of microorganisms. Although many are essential to maintaining the oral microbiota, some can cause oral infections such as caries, periodontitis, mucositis, and endodontic infections, and this is further exacerbated with dental [...] Read more.

The oral cavity serves as a nutrient-rich haven for over 600 species of microorganisms. Although many are essential to maintaining the oral microbiota, some can cause oral infections such as caries, periodontitis, mucositis, and endodontic infections, and this is further exacerbated with dental implants. Most of these infections are mixed species in nature and associated with a biofilm mode of growth. Here, after optimization of different parameters including cell density, growth media, and incubation conditions, we have developed an in vitro model of C. albicans–S. gordonii mixed-species biofilms on titanium discs that is relevant to infections of peri-implant diseases. Our results indicate a synergistic effect for the development of biofilms when both microorganisms were seeded together, confirming the existence of beneficial, mutualistic cross-kingdom interactions for biofilm formation. The morphological and architectural features of these dual-species biofilms formed on titanium were determined using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Mixed biofilms formed on titanium discs showed a high level of resistance to combination therapy with antifungal and antibacterial drugs. This model can serve as a platform for further analyses of complex fungal/bacterial biofilms and can also be applied to screening of new drug candidates against mixed-species biofilms. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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Review

Jump to: Research

18 pages, 1169 KiB

Open AccessReview

The Significance of Lipids to Biofilm Formation in Candida albicans: An Emerging Perspective

by Darakshan Alim, Shabnam Sircaik and Sneh Lata Panwar

J. Fungi 2018, 4(4), 140; https://doi.org/10.3390/jof4040140 - 18 Dec 2018

Cited by 41 | Viewed by 11476

Abstract

Candida albicans, the dimorphic opportunistic human fungal pathogen, is capable of forming highly drug-resistant biofilms in the human host. Formation of biofilm is a multistep and multiregulatory process involving various adaptive mechanisms. The ability of cells in a biofilm to alter membrane [...] Read more.

Candida albicans, the dimorphic opportunistic human fungal pathogen, is capable of forming highly drug-resistant biofilms in the human host. Formation of biofilm is a multistep and multiregulatory process involving various adaptive mechanisms. The ability of cells in a biofilm to alter membrane lipid composition is one such adaptation crucial for biofilm development in C. albicans. Lipids modulate mixed species biofilm formation in vivo and inherent antifungal resistance associated with these organized communities. Cells in C. albicans biofilms display phase-dependent changes in phospholipid classes and in levels of lipid raft formation. Systematic studies with genetically modified strains in which the membrane phospholipid composition can be manipulated are limited in C. albicans. In this review, we summarize the knowledge accumulated on the impact that alterations in phospholipids may have on the biofilm forming ability of C. albicans in the human host. This review may provide the requisite impetus to analyze lipids from a therapeutic standpoint in managing C. albicans biofilms. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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10 pages, 1364 KiB

Open AccessReview

Going with the Flo: The Role of Flo11-Dependent and Independent Interactions in Yeast Mat Formation

by Todd B. Reynolds

J. Fungi 2018, 4(4), 132; https://doi.org/10.3390/jof4040132 - 07 Dec 2018

Cited by 12 | Viewed by 5470

Abstract

Strains of the bakers’ yeast Saccharomyces cerevisiae that are able to generate a multicellular structure called a mat on low percentage (0.3%) agar plates are given a selective advantage over strains that cannot exhibit this phenotype. This environment may exhibit some similarities to [...] Read more.

Strains of the bakers’ yeast Saccharomyces cerevisiae that are able to generate a multicellular structure called a mat on low percentage (0.3%) agar plates are given a selective advantage over strains that cannot exhibit this phenotype. This environment may exhibit some similarities to the rotting fruit on which S. cerevisiae often grows in nature. Mat formation occurs when the cells spread over the plate as they grow, and cells in the center of the biofilm aggregate to form multicellular structures that resemble a floral pattern. This multicellular behavior is dependent on the cell surface flocculin Flo11. This review covers recent information on the structure of Flo11 and how this likely impacts mat formation as well as how variegated expression of Flo11 influences mat formation. Finally, it also discusses several Flo11-independent genetic factors that control mat formation, such as vacuolar protein sorting (VPS) genes, cell wall signaling components, and heat shock proteins. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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28 pages, 4731 KiB

Open AccessReview

Adhesins of Yeasts: Protein Structure and Interactions

by Ronnie G. Willaert

J. Fungi 2018, 4(4), 119; https://doi.org/10.3390/jof4040119 - 27 Oct 2018

Cited by 54 | Viewed by 7874

Abstract

The ability of yeast cells to adhere to other cells or substrates is crucial for many yeasts. The budding yeast Saccharomyces cerevisiae can switch from a unicellular lifestyle to a multicellular one. A crucial step in multicellular lifestyle adaptation is self-recognition, self-interaction, and [...] Read more.

The ability of yeast cells to adhere to other cells or substrates is crucial for many yeasts. The budding yeast Saccharomyces cerevisiae can switch from a unicellular lifestyle to a multicellular one. A crucial step in multicellular lifestyle adaptation is self-recognition, self-interaction, and adhesion to abiotic surfaces. Infectious yeast diseases such as candidiasis are initiated by the adhesion of the yeast cells to host cells. Adhesion is accomplished by adhesin proteins that are attached to the cell wall and stick out to interact with other cells or substrates. Protein structures give detailed insights into the molecular mechanism of adhesin-ligand interaction. Currently, only the structures of a very limited number of N-terminal adhesion domains of adhesins have been solved. Therefore, this review focuses on these adhesin protein families. The protein architectures, protein structures, and ligand interactions of the flocculation protein family of S. cerevisiae; the epithelial adhesion family of C. glabrata; and the agglutinin-like sequence protein family of C. albicans are reviewed and discussed. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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13 pages, 594 KiB

Open AccessReview

Tipping the Balance: C. albicans Adaptation in Polymicrobial Environments

by Amit Ranjan and Anna Dongari-Bagtzoglou

J. Fungi 2018, 4(3), 112; https://doi.org/10.3390/jof4030112 - 18 Sep 2018

Cited by 15 | Viewed by 4086

Abstract

Candida albicans is a pleiomorphic fungus which co-exists with commensal bacteria in mucosal and skin sites of mammalian hosts. It is also a major co-isolated organism from polymicrobial systemic infections, with high potential for morbidity or mortality in immunocompromised patients. Traditionally, resident mucosal [...] Read more.

Candida albicans is a pleiomorphic fungus which co-exists with commensal bacteria in mucosal and skin sites of mammalian hosts. It is also a major co-isolated organism from polymicrobial systemic infections, with high potential for morbidity or mortality in immunocompromised patients. Traditionally, resident mucosal bacteria have been thought to antagonize C. albicans in its ability to colonize or cause infection. However, recent investigations have revealed synergistic relationships with certain bacterial species that colonize the same mucosal sites with C. albicans. Such relationships broaden the research landscape in pathogenesis but also contribute to clinical challenges in the prevention or treatment of mucosal candidiasis. This review sheds light on interactions of C. albicans and mucosal bacteria, with special emphasis on the effects of the resident bacterial microbiota on C. albicans physiology as they relate to its adaptation in mucosal sites as a commensal colonizer or as a pathogenic organism. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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19 pages, 771 KiB

Open AccessReview

Cryptococcal Traits Mediating Adherence to Biotic and Abiotic Surfaces

by Emma Camacho and Arturo Casadevall

J. Fungi 2018, 4(3), 88; https://doi.org/10.3390/jof4030088 - 29 Jul 2018

Cited by 18 | Viewed by 6313

Abstract

Several species in the genus Cryptococcus are facultative intracellular pathogens capable of causing disease associated with high mortality and morbidity in humans. These fungi interact with other organisms in the soil, and these interactions may contribute to the development of adaptation mechanisms that [...] Read more.

Several species in the genus Cryptococcus are facultative intracellular pathogens capable of causing disease associated with high mortality and morbidity in humans. These fungi interact with other organisms in the soil, and these interactions may contribute to the development of adaptation mechanisms that function in virulence by promoting fungal survival in animal hosts. Fungal adhesion molecules, also known as adhesins, have been classically considered as cell-surface or secreted proteins that play critical roles in microbial pathogenesis or in biofilm formation as structural components. Pathogenic Cryptococcus spp. differ from other pathogenic yeasts in having a polysaccharide capsule that covers the cell wall surface and precludes interactions of those structures with host cell receptors. Hence, pathogenic Cryptococcus spp. use unconventional tools for surface attachment. In this essay, we review the unique traits and mechanisms favoring adhesion of Cryptococcus spp. to biotic and abiotic surfaces. Knowledge of the traits that mediate adherence could be exploited in the development of therapeutic, biomedical, and/or industrial products. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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16 pages, 1129 KiB

Open AccessReview

Candida glabrata’s Genome Plasticity Confers a Unique Pattern of Expressed Cell Wall Proteins

by Eunice López-Fuentes, Guadalupe Gutiérrez-Escobedo, Bea Timmermans, Patrick Van Dijck, Alejandro De Las Peñas and Irene Castaño

J. Fungi 2018, 4(2), 67; https://doi.org/10.3390/jof4020067 - 05 Jun 2018

Cited by 23 | Viewed by 4021

Abstract

Candida glabrata is the second most common cause of candidemia, and its ability to adhere to different host cell types, to microorganisms, and to medical devices are important virulence factors. Here, we consider three characteristics that confer extraordinary advantages to C. glabrata within [...] Read more.

Candida glabrata is the second most common cause of candidemia, and its ability to adhere to different host cell types, to microorganisms, and to medical devices are important virulence factors. Here, we consider three characteristics that confer extraordinary advantages to C. glabrata within the host. (1) C. glabrata has a large number of genes encoding for adhesins most of which are localized at subtelomeric regions. The number and sequence of these genes varies substantially depending on the strain, indicating that C. glabrata can tolerate high genomic plasticity; (2) The largest family of CWPs (cell wall proteins) is the EPA (epithelial adhesin) family of adhesins. Epa1 is the major adhesin and mediates adherence to epithelial, endothelial and immune cells. Several layers of regulation like subtelomeric silencing, cis-acting regulatory regions, activators, nutritional signaling, and stress conditions tightly regulate the expression of many adhesin-encoding genes in C. glabrata, while many others are not expressed. Importantly, there is a connection between acquired resistance to xenobiotics and increased adherence; (3) Other subfamilies of adhesins mediate adherence to Candida albicans, allowing C. glabrata to efficiently invade the oral epithelium and form robust biofilms. It is noteworthy that every C. glabrata strain analyzed presents a unique pattern of CWPs at the cell surface. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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16 pages, 1612 KiB

Open AccessReview

Adhesins in Candida glabrata

by Bea Timmermans, Alejandro De Las Peñas, Irene Castaño and Patrick Van Dijck

J. Fungi 2018, 4(2), 60; https://doi.org/10.3390/jof4020060 - 20 May 2018

Cited by 62 | Viewed by 6252

Abstract

The human fungal pathogen Candida glabrata is causing more and more problems in hospitals, as this species shows an intrinsic antifungal drug resistance or rapidly becomes resistant when challenged with antifungals. C. glabrata only grows in the yeast form, so it is lacking [...] Read more.

The human fungal pathogen Candida glabrata is causing more and more problems in hospitals, as this species shows an intrinsic antifungal drug resistance or rapidly becomes resistant when challenged with antifungals. C. glabrata only grows in the yeast form, so it is lacking a yeast-to-hyphae switch, which is one of the main virulence factors of C. albicans. An important virulence factor of C. glabrata is its capacity to strongly adhere to many different substrates. To achieve this, C. glabrata expresses a large number of adhesin-encoding genes and genome comparisons with closely related species, including the non-pathogenic S. cerevisiae, which revealed a correlation between the number of adhesin-encoding genes and pathogenicity. The adhesins are involved in the first steps during an infection; they are the first point of contact with the host. For several of these adhesins, their importance in adherence to different substrates and subsequent biofilm formation was demonstrated in vitro or in vivo. In this review, we provide an overview of the role of C. glabrata adhesins during adhesion and biofilm formation both, under in vitro and in vivo conditions. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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20 pages, 1296 KiB

Open AccessReview

What We Do Not Know about Fungal Cell Adhesion Molecules

by Peter N. Lipke

J. Fungi 2018, 4(2), 59; https://doi.org/10.3390/jof4020059 - 17 May 2018

Cited by 60 | Viewed by 7307

Abstract

There has been extensive research on structure and function of fungal cell adhesion molecules, but the most of the work has been about adhesins in Candida albicans and Saccharomyces cerevisiae. These yeasts are members of a single ascomycete order, and adhesion molecules from [...] Read more.

There has been extensive research on structure and function of fungal cell adhesion molecules, but the most of the work has been about adhesins in Candida albicans and Saccharomyces cerevisiae. These yeasts are members of a single ascomycete order, and adhesion molecules from the six other fungal phyla are only sparsely described in the literature. In these other phyla, most of the research is at the cellular level, rather than at the molecular level, so there has been little characterization of the adhesion molecules themselves. A catalog of known adhesins shows some common features: high Ser/Thr content, tandem repeats, N- and O-glycosylations, GPI anchors, dibasic sequence motifs, and potential amyloid-forming sequences. However, none of these features is universal. Known ligands include proteins and glycans on homologous cells and host cells. Existing and novel tools can exploit the availability of genome sequences to identify and characterize new fungal adhesins. These include bioinformatics tools and well-established yeast surface display models, which could be coupled with an adhesion substrate array. Thus, new knowledge could be exploited to answer key questions in fungal ecology, animal and plant pathogenesis, and roles of biofilms in infection and biomass turnover. Full article

(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)

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