Antimicrobial Resistance: What Can We Learn from Genomics?

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Genetic and Biochemical Studies of Antibiotic Activity and Resistance".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 12565

Special Issue Editors

Associate Professor (Docent) of Medical Microbiology, University of Helsinki, Helsinki, Finland
Interests: genomics; metagenomics; microbiology; bioinformatics; viromics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Virology, University of Helsinki, Helsinki, Finland
Interests: One Health; microbiology and microbial evolution; zoonoses; emerging infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Internationalization and industrialization have dramatically changed the vulnerability of human and animal populations to emerging and re-emerging infectious diseases, changing both the scale and pace of disease outbreaks. Luckily, over the past decade, the development of high-throughput sequencing has facilitated considerable progress in the detection pathogens and strategies for outbreak response efforts. It is now feasible to sequence the genome of a pathogen rapidly, economically, and with high sensitivity, transforming the fields of diagnostics, surveillance, and pathogenesis.

Here, in this Special Issue, we aim to provide an insight into the genomic/comparative/metagenomic research on antimicrobial-resistant pathogens. Researchers are invited to submit both original research papers and review articles on studies related to the genomics of different antimicrobial-resistant pathogens using the comparative genomics or metagenomics approach. Other papers present results to predict or track antimicrobial resistance based on genome sequences are also welcome.

Dr. Ravi Kant
Dr. Tarja Sironen
Guest Editors

Manuscript Submission Information

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Keywords

  • genomics
  • comparative genomics
  • metagenomics
  • microbiology
  • emerging infections
  • pathogens
  • bioinformatics

Published Papers (6 papers)

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Research

17 pages, 6145 KiB  
Article
Whole Genome Sequencing Reveals Antimicrobial Resistance and Virulence Genes of Both Pathogenic and Non-Pathogenic B. cereus Group Isolates from Foodstuffs in Thailand
by Phornphan Sornchuer, Kritsakorn Saninjuk, Sumet Amonyingcharoen, Jittiporn Ruangtong, Nattaya Thongsepee, Pongsakorn Martviset, Pathanin Chantree and Kant Sangpairoj
Antibiotics 2024, 13(3), 245; https://doi.org/10.3390/antibiotics13030245 - 07 Mar 2024
Viewed by 1171
Abstract
Members of the Bacillus cereus group are spore-forming Gram-positive bacilli that are commonly associated with diarrheal or emetic food poisoning. They are widespread in nature and frequently present in both raw and processed food products. Here, we genetically characterized 24 B. cereus group [...] Read more.
Members of the Bacillus cereus group are spore-forming Gram-positive bacilli that are commonly associated with diarrheal or emetic food poisoning. They are widespread in nature and frequently present in both raw and processed food products. Here, we genetically characterized 24 B. cereus group isolates from foodstuffs. Whole-genome sequencing (WGS) revealed that most of the isolates were closely related to B. cereus sensu stricto (12 isolates), followed by B. pacificus (5 isolates), B. paranthracis (5 isolates), B. tropicus (1 isolate), and “B. bingmayongensis” (1 isolate). The most detected virulence genes were BAS_RS06430, followed by bacillibactin biosynthesis genes (dhbA, dhbB, dhbC, dhbE, and dhbF), genes encoding the three-component non-hemolytic enterotoxin (nheA, nheB, and nheC), a gene encoding an iron-regulated leucine-rich surface protein (ilsA), and a gene encoding a metalloprotease (inhA). Various biofilm-associated genes were found, with high prevalences of tasA and sipW genes (matrix protein-encoding genes); purA, purC, and purL genes (eDNA synthesis genes); lytR and ugd genes (matrix polysaccharide synthesis genes); and abrB, codY, nprR, plcR, sinR, and spo0A genes (biofilm transcription regulator genes). Genes related to fosfomycin and beta-lactam resistance were identified in most of the isolates. We therefore demonstrated that WGS analysis represents a useful tool for rapidly identifying and characterizing B. cereus group strains. Determining the genetic epidemiology, the presence of virulence and antimicrobial resistance genes, and the pathogenic potential of each strain is crucial for improving the risk assessment of foodborne B. cereus group strains. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: What Can We Learn from Genomics?)
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12 pages, 1640 KiB  
Article
Associations between Isolation Source, Clonal Composition, and Antibiotic Resistance Genes in Escherichia coli Collected in Washington State, USA
by Mary Jewell, Erica R. Fuhrmeister, Marilyn C. Roberts, Scott J. Weissman, Peter M. Rabinowitz and Stephen E. Hawes
Antibiotics 2024, 13(1), 103; https://doi.org/10.3390/antibiotics13010103 - 20 Jan 2024
Viewed by 1205
Abstract
Antimicrobial resistance (AMR) is a global health problem stemming from the use of antibiotics in humans, animals, and the environment. This study used whole-genome sequencing (WGS) of E. coli to explore patterns of AMR across sectors in Washington State, USA (WA). The WGS [...] Read more.
Antimicrobial resistance (AMR) is a global health problem stemming from the use of antibiotics in humans, animals, and the environment. This study used whole-genome sequencing (WGS) of E. coli to explore patterns of AMR across sectors in Washington State, USA (WA). The WGS data from 1449 E. coli isolates were evaluated for isolation source (humans, animals, food, or the environment) and the presence of antibiotic resistance genes (ARGs). We performed sequence typing using PubMLST and used ResFinder to identify ARGs. We categorized isolates as being pan-susceptible, resistant, or multidrug-resistant (MDR), defined as carrying resistance genes for at least three or more antimicrobial drug classes. In total, 60% of isolates were pan-susceptible, while 18% were resistant, and 22% exhibited MDR. The proportion of resistant isolates varied significantly according to the source of the isolates (p < 0.001). The greatest resistance was detected in isolates from humans and then animals, while environmental isolates showed the least resistance. This study demonstrates the feasibility of comparing AMR across various sectors in Washington using WGS and a One Health approach. Such analysis can complement other efforts for AMR surveillance and potentially lead to targeted interventions and monitoring activities to reduce the overall burden of AMR. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: What Can We Learn from Genomics?)
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19 pages, 2821 KiB  
Article
Genomic Characterization of International High-Risk Clone ST410 Escherichia coli Co-Harboring ESBL-Encoding Genes and blaNDM-5 on IncFIA/IncFIB/IncFII/IncQ1 Multireplicon Plasmid and Carrying a Chromosome-Borne blaCMY-2 from Egypt
by Nelly M. Mohamed, Azza S. Zakaria and Eva A. Edward
Antibiotics 2022, 11(8), 1031; https://doi.org/10.3390/antibiotics11081031 - 30 Jul 2022
Cited by 8 | Viewed by 1897
Abstract
The accelerated dispersion of multidrug-resistant (MDR) Escherichia coli due to the production of extended-spectrum β-lactamases (ESBLs) or AmpC enzymes has been noted in Egypt, presenting a serious treatment challenge. In this study, we investigate the prevalence of ESBLs and AmpC enzymes among 48 [...] Read more.
The accelerated dispersion of multidrug-resistant (MDR) Escherichia coli due to the production of extended-spectrum β-lactamases (ESBLs) or AmpC enzymes has been noted in Egypt, presenting a serious treatment challenge. In this study, we investigate the prevalence of ESBLs and AmpC enzymes among 48 E. coli isolates collected from patients with urinary tract infections admitted to a teaching hospital in Alexandria. Phenotypic and genotypic methods of detection are conducted. Isolates producing both enzymes are tested for the mobilization of their genes by a broth mating experiment. Whole genome sequencing (WGS) is performed for isolate EC13655. The results indicate that 80% of the isolates are MDR, among which 52% and 13% were ESBL and AmpC producers, respectively. Conjugation experiments fail to show the mobilization of blaCMY-2 in EC13655, which was chosen for WGS. In silico analysis reveals that the isolate belongs to a ST410-H24Rx high-risk clone. It coharbors the ESBL-encoding genes blaCTX-M-15, blaTEM-1, blaOXA-1 and blaNDM-5 on an IncFIA/IncFIB/IncFII/IncQ1 multireplicon plasmid. The chromosomal location of blaCMY-2 is detected with a flanking upstream copy of ISEcp1. This chromosomal integration of blaCMY-2 establishes the stable maintenance of the gene and thus, necessitates an imperative local surveillance to reduce further spread of such strains in different clinical settings. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: What Can We Learn from Genomics?)
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15 pages, 1898 KiB  
Article
Whole-Genome Sequence of Multidrug-Resistant Methicillin-Resistant Staphylococcus epidermidis Carrying Biofilm-Associated Genes and a Unique Composite of SCCmec
by Hisham N. Altayb, Hana S. Elbadawi, Othman Baothman, Imran Kazmi, Faisal A. Alzahrani, Muhammad Shahid Nadeem, Salman Hosawi and Kamel Chaieb
Antibiotics 2022, 11(7), 861; https://doi.org/10.3390/antibiotics11070861 - 24 Jun 2022
Cited by 2 | Viewed by 2086
Abstract
Staphylococcus epidermidis is part of the normal human flora that has recently become an important opportunistic pathogen causing nosocomial infections and tends to be multidrug-resistant. In this investigation, we aimed to study the genomic characteristics of methicillin-resistant S. epidermidis isolated from clinical specimens. [...] Read more.
Staphylococcus epidermidis is part of the normal human flora that has recently become an important opportunistic pathogen causing nosocomial infections and tends to be multidrug-resistant. In this investigation, we aimed to study the genomic characteristics of methicillin-resistant S. epidermidis isolated from clinical specimens. Three isolates were identified using biochemical tests and evaluated for drug susceptibility. Genomic DNA sequences were obtained using Illumina, and were processed for analysis using various bioinformatics tools. The isolates showed multidrug resistance to most of the antibiotics tested in this study, and were identified with three types (III(3A), IV(2B&5), and VI(4B)) of the mobile genetic element SCCmec that carries the methicillin resistance gene (mecA) and its regulators (mecI and mecR1). A total of 11 antimicrobial resistance genes (ARGs) was identified as chromosomally mediated or in plasmids; these genes encode for proteins causing decreased susceptibility to methicillin (mecA), penicillin (blaZ), fusidic acid (fusB), fosfomycin (fosB), tetracycline (tet(K)), aminoglycosides (aadD, aac(6′)-aph(2′’)), fluoroquinolone (MFS antibiotic efflux pump), trimethoprim (dfrG), macrolide (msr(A)), and chlorhexidine (qacA)). Additionally, the 9SE strain belongs to the globally disseminated ST2, and harbors biofilm-formation genes (icaA, icaB, icaC, icaD, and IS256) with phenotypic biofilm production capability. It also harbors the fusidic acid resistance gene (fusB), which could increase the risk of device-associated healthcare infections, and 9SE has been identified as having a unique extra SCC gene (ccrB4); this new composite element of the ccr type needs more focus to better understand its role in the drug resistance mechanism. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: What Can We Learn from Genomics?)
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12 pages, 1658 KiB  
Article
Comparative Genomics of 42 Arcanobacterium phocae Strains
by Kirsi J. Aaltonen, Ravi Kant, Nanett Kvist Nikolaisen, Mikkel Lindegaard, Mirja Raunio-Saarnisto, Lars Paulin, Olli Vapalahti and Tarja Sironen
Antibiotics 2021, 10(6), 740; https://doi.org/10.3390/antibiotics10060740 - 18 Jun 2021
Cited by 1 | Viewed by 2041
Abstract
For the last 13 years, the fur industry in Europe has suffered from epidemic spouts of a severe necrotizing pyoderma. It affects all species currently farmed for fur and causes animal welfare problems and significant losses to the farmers. The causative agent of [...] Read more.
For the last 13 years, the fur industry in Europe has suffered from epidemic spouts of a severe necrotizing pyoderma. It affects all species currently farmed for fur and causes animal welfare problems and significant losses to the farmers. The causative agent of this disease was identified as Arcanobacterium phocae. Previously, this bacterium has been isolated from seals and other marine mammals, apparently causing wound and lung infections. Attempts at antibiotic treatment have been unsuccessful and the current advice on preventing the disease is to cull all animals with clinical signs. This poses an urgent question regarding possible vaccine development, as well as the need for further understanding of the pathogenicity of this organism. This study compared the whole genomes of 42 A. phocae strains isolated from seals, blue foxes, finnraccoons, mink and otter. The sequences were created using the Illumina technology and annotations were done using the RAST pipeline. A phylogenetic analysis identified a clear separation between the seal strains and the fur-animal-derived isolates, but also indicated that the bacterium readily adapts to new environments and host species with reasonable diversity. A pan- and core-genome was created and analyzed for proteins. A further analysis identified several virulence factors as well as multiple putative and secreted proteins of special interest for vaccine development. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: What Can We Learn from Genomics?)
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11 pages, 1885 KiB  
Article
Pan and Core Genome Analysis of 183 Mycobacterium tuberculosis Strains Revealed a High Inter-Species Diversity among the Human Adapted Strains
by Fathiah Zakham, Tarja Sironen, Olli Vapalahti and Ravi Kant
Antibiotics 2021, 10(5), 500; https://doi.org/10.3390/antibiotics10050500 - 28 Apr 2021
Cited by 9 | Viewed by 2551
Abstract
Tuberculosis (TB) is an airborne communicable disease with high morbidity and mortality rates, especially in developing countries. The causal agents of TB belong to the complex Mycobacterium tuberculosis (MTBc), which is composed of different human and animal TB associated species. Some animal associated [...] Read more.
Tuberculosis (TB) is an airborne communicable disease with high morbidity and mortality rates, especially in developing countries. The causal agents of TB belong to the complex Mycobacterium tuberculosis (MTBc), which is composed of different human and animal TB associated species. Some animal associated species have zoonotic potential and add to the burden of TB management. The BCG (“Bacillus Calmette-Guérin”) vaccine is widely used for the prevention against TB, but its use is limited in immunocompromised patients and animals due to the adverse effects and disseminated life-threatening complications. In this study, we aimed to carry out a comparative genome analysis between the human adapted species including BCG vaccine strains to identify and pinpoint the conserved genes related to the virulence across all the species, which could add a new value for vaccine development. For this purpose, the sequences of 183 Mycobacterium tuberculosis (MTB) strains were retrieved from the freely available WGS dataset at NCBI. The species included: 168 sensu stricto MTB species with other human MTB complex associated strains: M. tuberculosis var. africanum (3), M. tuberculosis var. bovis (2 draft genomes) and 10 BCG species, which enabled the analysis of core genome which contains the conserved genes and some virulence factor determinants. Further, a phylogenetic tree was constructed including the genomes of human (183); animals MTB adapted strains (6) and the environmental Mycobacterium strain “M. canettii”. Our results showed that the core genome consists of 1166 conserved genes among these species, which represents a small portion of the pangenome (7036 genes). The remaining genes in the pangenome (5870) are accessory genes, adding a high inter-species diversity. Further, the core genome includes several virulence-associated genes and this could explain the rare infectiousness potential of some attenuated vaccine strains in some patients. This study reveals that low number of conserved genes in human adapted MTBc species and high inter-species diversity of the pan-genome could be considered for vaccine candidate development. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: What Can We Learn from Genomics?)
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