Special Issue "Genetics, Genomics and Pathogenesis of Staphylococcus aureus"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Microbial Genetics and Genomics".

Deadline for manuscript submissions: closed (13 August 2021).

Special Issue Editors

Dr. Patrice Francois
E-Mail Website
Guest Editor
Genomic Research Laboratory, Service of Infectious Diseases, Medical University Center, Geneva University Hospitals, CH-1211 Geneva, Switzerland
Interests: Staphylococcus aureus; infectious diseases; foodborne pathogens; antibiotic resistance; pathogenicity; genomics; transcriptomic; bacteriophages
Dr. Nathalie L. van Der Mee-Marquet
E-Mail Website
Guest Editor
UMR 1282 Infectiologie Santé Publique, Université de Tours, 37020 Tours, France
Interests: Staphylococcus aureus; bacteriophages; plasmids and other mobile genetic elements; foodborne pathogens; antimicrobial resistance; pathogenicity

Special Issue Information

Dear Colleagues,

Staphylococcus aureus is a versatile human and veterinary pathogenic bacterium recognized as a worldwide health problem. S. aureus is responsible for a wide spectrum of infections, ranging from local skin to severe disseminated diseases. In humans, these infections include acute diseases such as endocarditis, furunculosis or food poisoning but also chronic infections such as osteomyelitis, rhinosinusitis or otitis media. Nonetheless, approximately 20–30% of the general population carries S. aureus asymptomatically for decades.

Methicillin-resistant Staphylococcus aureus emerged rapidly after the introduction of methicillin and has become a worldwide problem in developed countries since the 1980s. Infections due to S. aureus (or MRSA) are particularly diverse in terms of host, infected tissues, as well as severity and are generally difficult to eradicate. The versatility of this pathogen could be explained by different adaptative strategies and virulence properties. For instance, S. aureus is capable of surviving in remarkably diverse environmental conditions (acidic, oxidant, non-physiological osmotic pressure, and desiccation, lack of nutrients and presence of host factors). S. aureus synthesizes a plethora of virulence factors, including cell-surface-associated proteins, toxins/exotoxins, and hydrolytic enzymes that facilitate attachment, colonization, and cell–cell interactions in various hosts. In addition, this organism can evade immune defenses by forming biofilm, through the induction of specific defense genes (catalase, superoxide dismutase, etc.) or by expressing immunomodulatory molecules allowing escape from host defenses. The roles of these bacterial compounds have been documented in part, in different experimental models of acute or chronic infections. The other factor that facilitates the invasive strategy is the ability of the bacterium to benefit from genome plasticity, allowing acquisition of foreign DNA, either from other species or from homologous bacterial species, enabling it to rapidly remodel its genome yielding to a super-bug genotype.

Despite this important diversity of clinical presentation and physiopathology, the totality of clinical manifestations and symptoms are due to only 8–10 different bacterial lineages. This observation suggests that the bacterium would be highly variable in terms of genomic features and ability to interact with a variety of compounds, niches, tissues or cells. These mechanisms are related to modulation of gene expression but also to intrinsic genome composition. The percentage of conserved open reading frames (ORFs) throughout the genomes represents roughly 75% of genes constituting the core genome. These include essential genes that encode cell survival functions, maintain housekeeping, facilitate bacterial central metabolism, and synthesize and replicate DNA and RNA. Conversely, 25% of the genomic content represents accessory genes. About half of these accessory genes consist of mobile genetic elements (MGEs) that play a central role in adaptation processes and in genetic evolution. Considering that approximately 50% of annotated genes have an unknown function, studies of the content and most importantly the expression of all S. aureus genomic features should contribute to document the steps required during bacteria and host interaction. The general regulatory processes at the level of the whole cell, mediating organized gene expression, also represent a major element considering S. aureus virulence. During the last 2 decades, dramatic improvements in high-throughput sequencing technology have allowed studying the diversity and content of some S. aureus populations representative of specific clinical settings and performing transcriptomic studies at the whole cell level to explore complex regulatory pathways during exposition to specific environments.

The aim of this Special Issue is to summarize the molecular mechanisms mainly driven by the accessory genome of S. aureus using genomic and transcriptomic methods, allowing us to improve our knowledge and comprehension of pathogenesis and physio-pathogenic aspects of S. aureus behavior in contact with an infected host.

Dr. Patrice Francois
Dr. Nathalie L. van Der Mee-Marquet
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Staphylococcus aureus
  • genomics
  • trancriptomic
  • regulation
  • virulence factors
  • biofilm
  • epidemiology
  • human infection
  • prophages
  • genome plasticity
  • virulence
  • molecular mechanisms

Published Papers (5 papers)

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Research

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Article
The Persistence of Staphylococcus aureus in Pressure Ulcers: A Colonising Role
Genes 2021, 12(12), 1883; https://doi.org/10.3390/genes12121883 - 25 Nov 2021
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Abstract
Decubitus pressure ulcers (PU) are a major complication of immobilised patients. Staphylococcus aureus is one of the most frequently detected microorganisms in PU samples; however, its persistence and role in the evolution of these wounds is unknown. In this study, we analysed S. [...] Read more.
Decubitus pressure ulcers (PU) are a major complication of immobilised patients. Staphylococcus aureus is one of the most frequently detected microorganisms in PU samples; however, its persistence and role in the evolution of these wounds is unknown. In this study, we analysed S. aureus strains isolated from PU biopsies at inclusion and day 28. Eleven S. aureus (21.1%) were detected in 52 patients at inclusion. Only six PUs (11.5%) continued to harbour this bacterium at day 28. Using a whole genome sequencing approach (Miseq®, Illumina), we confirmed that these six S. aureus samples isolated at D28 were the same strain as that isolated at inclusion, with less than 83 bp difference. Phenotypical studies evaluating the growth profiles (Infinite M Mano, Tecan®) and biofilm formation (Biofilm Ring Test®) did not detect any significant difference in the fitness of the pairs of S. aureus. However, using the Caenorhabditis elegans killing assay, a clear decrease of virulence was observed between strains isolated at D28 compared with those isolated at inclusion, regardless of the clinical evolution of the PU. Moreover, all strains at inclusion were less virulent than a control S. aureus strain, i.e., NSA739. An analysis of polymicrobial communities of PU (by metabarcoding approach), in which S. aureus persisted, demonstrated no impact of Staphylococcus genus on PU evolution. Our study suggested that S. aureus presented a colonising profile on PU with no influence on wound evolution. Full article
(This article belongs to the Special Issue Genetics, Genomics and Pathogenesis of Staphylococcus aureus)
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Article
Impact of Bicarbonate-β-Lactam Exposures on Methicillin-Resistant Staphylococcus aureus (MRSA) Gene Expression in Bicarbonate-β-Lactam-Responsive vs. Non-Responsive Strains
Genes 2021, 12(11), 1650; https://doi.org/10.3390/genes12111650 - 20 Oct 2021
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Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a difficult clinical treatment issue. Recently, a novel phenotype was discovered amongst selected MRSA which exhibited enhanced β-lactam susceptibility in vitro in the presence of NaHCO3 (termed ‘NaHCO3-responsiveness’). This increased β-lactam susceptibility phenotype [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a difficult clinical treatment issue. Recently, a novel phenotype was discovered amongst selected MRSA which exhibited enhanced β-lactam susceptibility in vitro in the presence of NaHCO3 (termed ‘NaHCO3-responsiveness’). This increased β-lactam susceptibility phenotype has been verified in both ex vivo and in vivo models. Mechanistic studies to-date have implicated NaHCO3-mediated repression of genes involved in the production, as well as maturation, of the alternative penicillin-binding protein (PBP) 2a, a necessary component of MRSA β-lactam resistance. Herein, we utilized RNA-sequencing (RNA-seq) to identify genes that were differentially expressed in NaHCO3-responsive (MRSA 11/11) vs. non-responsive (COL) strains, in the presence vs. absence of NaHCO3-β-lactam co-exposures. These investigations revealed that NaHCO3 selectively repressed the expression of a cadre of genes in strain 11/11 known to be a part of the sigB-sarA-agr regulon, as well as a number of genes involved in the anchoring of cell wall proteins in MRSA. Moreover, several genes related to autolysis, cell division, and cell wall biosynthesis/remodeling, were also selectively impacted by NaHCO3-OXA exposure in the NaHCO3-responsive strain MRSA 11/11. These outcomes provide an important framework for further studies to mechanistically verify the functional relevance of these genetic perturbations to the NaHCO3-responsiveness phenotype in MRSA. Full article
(This article belongs to the Special Issue Genetics, Genomics and Pathogenesis of Staphylococcus aureus)
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Article
Co-Carriage of Metal and Antibiotic Resistance Genes in Sewage Associated Staphylococci
Genes 2021, 12(10), 1473; https://doi.org/10.3390/genes12101473 - 23 Sep 2021
Viewed by 355
Abstract
Controlling spread of resistance genes from wastewater to aquatic systems requires more knowledge on how resistance genes are acquired and transmitted. Whole genomic sequences from sewage-associated staphylococcus isolates (20 S. aureus, 2 Staphylococcus warneri, and 2 Staphylococcus delphini) were analyzed [...] Read more.
Controlling spread of resistance genes from wastewater to aquatic systems requires more knowledge on how resistance genes are acquired and transmitted. Whole genomic sequences from sewage-associated staphylococcus isolates (20 S. aureus, 2 Staphylococcus warneri, and 2 Staphylococcus delphini) were analyzed for the presence of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs). Plasmid sequences were identified in each isolate to investigate co-carriage of ARGs and MRGs within. BLASTN analysis showed that 67% of the isolates carried more than one ARG. The carriage of multiple plasmids was observed more in CC5 than CC8 S. aureus strains. Plasmid exchange was observed in all staphylococcus species except the two S. delphini isolates that carried multiple MRGs, no ARGs, and no plasmids. 85% of S. aureus isolates carried the blaZ gene, 76% co-carried blaZ with cadD and cadX, with 62% of these isolates carrying blaZ, cadD, and cadX on the same plasmid. The co-carriage of ARGs and MRGs in S. warneri isolates, and carriage of MRGs in S. delphini, without plasmids suggests non-conjugative transmission routes for gene acquisition. More studies are required that focus on the transduction and transformation routes of transmission to prevent interspecies exchange of ARGs and MRGs in sewage-associated systems. Full article
(This article belongs to the Special Issue Genetics, Genomics and Pathogenesis of Staphylococcus aureus)
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Review

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Review
The Staphylococcus aureus CC398 Lineage: An Evolution Driven by the Acquisition of Prophages and Other Mobile Genetic Elements
Genes 2021, 12(11), 1752; https://doi.org/10.3390/genes12111752 - 30 Oct 2021
Viewed by 299
Abstract
Among clinically relevant lineages of Staphylococcus aureus, the lineage or clonal complex 398 (CC398) is of particular interest. Strains from this lineage were only described as livestock colonizers until 2007. Progressively, cases of infection were reported in humans in contact with farm [...] Read more.
Among clinically relevant lineages of Staphylococcus aureus, the lineage or clonal complex 398 (CC398) is of particular interest. Strains from this lineage were only described as livestock colonizers until 2007. Progressively, cases of infection were reported in humans in contact with farm animals, and now, CC398 isolates are increasingly identified as the cause of severe infections even in patients without any contact with animals. These observations suggest that CC398 isolates have spread not only in the community but also in the hospital setting. In addition, several recent studies have reported that CC398 strains are evolving towards increased virulence and antibiotic resistance. Identification of the origin and emergence of this clonal complex could probably benefit future large-scale studies that aim to detect sources of contamination and infection. Current evidence indicates that the evolution of CC398 strains towards these phenotypes has been driven by the acquisition of prophages and other mobile genetic elements. In this short review, we summarize the main knowledge of this major lineage of S. aureus that has become predominant in the human clinic worldwide within a single decade. Full article
(This article belongs to the Special Issue Genetics, Genomics and Pathogenesis of Staphylococcus aureus)
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Review
Antibacterial Peptides Resistance in Staphylococcus aureus: Various Mechanisms and the Association with Pathogenicity
Genes 2021, 12(10), 1527; https://doi.org/10.3390/genes12101527 - 28 Sep 2021
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Abstract
Staphylococcus aureus is a bacterium that mainly colonizes the nasal cavity and skin. To colonize the host, it is necessary for S. aureus to resist many antibacterial factors derived from human and commensal bacteria. Among them are the bacteria-derived antimicrobial peptides (AMPs) called [...] Read more.
Staphylococcus aureus is a bacterium that mainly colonizes the nasal cavity and skin. To colonize the host, it is necessary for S. aureus to resist many antibacterial factors derived from human and commensal bacteria. Among them are the bacteria-derived antimicrobial peptides (AMPs) called bacteriocins. It was reported that some two-component systems (TCSs), which are signal transduction systems specific to bacteria, are involved in the resistance to several bacteriocins in S. aureus. However, the TCS-mediated resistance is limited to relatively low concentrations of bacteriocins, while high concentrations of bacteriocins still exhibit antibacterial activity against S. aureus. To determine whether we could obtain highly bacteriocin-resistant mutants, we tried to isolate highly nisin A-resistant mutants by exposing the cells to sub-minimum inhibitory concentrations (MICs) of nisin A. Nisin A is one of the bacteriocins produced by Lactococcus lactis and is utilized as a food preservative worldwide. Finally, we obtained highly nisin A-resistant mutants with mutations in one TCS, BraRS, and in PmtR, which is involved in the expression of pmtABCD. Notably, some highly resistant strains also showed increased pathogenicity. Based on our findings, this review provides up-to-date information on the role of TCSs in the susceptibility to antibacterial peptides. Additionally, the mechanism for high antimicrobial peptides resistance and its association with pathogenicity in S. aureus is elucidated. Full article
(This article belongs to the Special Issue Genetics, Genomics and Pathogenesis of Staphylococcus aureus)
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