Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of Virulent and Non-virulent Staphylococcus aureus Strains

Bonar, Emilia; Bukowski, Michal; Hydzik, Marcin; Jankowska, Urszula; Kędracka–Krok, Sylwia; Groborz, Magdalena; Dubin, Grzegorz; Akkerboom, Viktoria; Międzobrodzki, Jacek; Sabat, Artur J.; Friedrich, Alexander; Władyka, Benedykt

doi:10.3389/fcimb.2018.00313

Cited by 10 publications

(4 citation statements)

References 70 publications

(90 reference statements)

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“…Poultry strains of S. aureus used in this study have been described previously elsewhere (Lowder et al, 2009; Polakowska et al, 2012; Bonar et al, 2016, 2018). The summary is included in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Prevalence of Antibiotic and Heavy Metal Resistance Determinants and Virulence-Related Genetic Elements in Plasmids of Staphylococcus aureus

et al. 2019

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The use of antibiotics on a mass scale, particularly in farming, and their release into the environment has led to a rapid emergence of resistant bacteria. Once emerged, resistance determinants are spread by horizontal gene transfer among strains of the same as well as disparate bacterial species. Their accumulation in free-living as well as livestock and community-associated strains results in the widespread multiple-drug resistance among clinically relevant species posing an increasingly pressing problem in healthcare. One of these clinically relevant species is Staphylococcus aureus , a common cause of hospital and community outbreaks. Among the rich diversity of mobile genetic elements regularly occurring in S. aureus such as phages, pathogenicity islands, and staphylococcal cassette chromosomes, plasmids are the major mean for dissemination of resistance determinants and virulence factors. Unfortunately, a vast number of whole-genome sequencing projects does not aim for complete sequence determination, which results in a disproportionately low number of known complete plasmid sequences. To address this problem we determined complete plasmid sequences derived from 18 poultry S. aureus strains and analyzed the prevalence of antibiotic and heavy metal resistance determinants, genes of virulence factors, as well as genetic elements relevant for their maintenance. Some of the plasmids have been reported before and are being found in clinical isolates of strains typical for humans or human ones of livestock origin. This shows that livestock-associated staphylococci are a significant reservoir of resistance determinants and virulence factors. Nevertheless, nearly half of the plasmids were unknown to date. In this group we found a potentially mobilizable plasmid pPA3 being a unique example of accumulation of resistance determinants and virulence factors likely stabilized by a presence of a toxin–antitoxin system.

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Section: Methodsmentioning

confidence: 99%

Prevalence of Antibiotic and Heavy Metal Resistance Determinants and Virulence-Related Genetic Elements in Plasmids of Staphylococcus aureus

et al. 2019

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“…Prophage mΦ11 promotes USA300-mediated tissue damage by increasing skin abscess size during murine infection (Figure S1A) , as previously reported (5). Often, hypervirulent strains of S. aureus will exhibit differences in growth rates (17), secreted protein production (18), and/or transcriptional profiles (19-21). However, strain USA300 LAC* harboring mΦ11 did not show significantly altered in vitro growth kinetics, exoprotein production, hemolysis patterns, or transcript levels of non-mΦ11 genes compared to the parental USA300 LAC*, as determined by RNA sequencing analysis (Figures S1B-E) .…”

Section: Resultsmentioning

confidence: 99%

Prophage-encoded methyltransferase drives adaptation of community-acquired methicillin-resistantStaphylococcus aureus

Ulrich,

Podkowik,

Tierce

et al. 2024

Preprint

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We recently described the evolution of a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 variant responsible for an outbreak of skin and soft tissue infections. Acquisition of a mosaic version of the Φ11 prophage (mΦ11) that increases skin abscess size was an early step in CA-MRSA adaptation that primed the successful spread of the clone. The present report shows how prophage mΦ11 exerts its effect on virulence for skin infection without encoding a known toxin or fitness genes. Abscess size and skin inflammation were associated with DNA methylase activity of an mΦ11-encoded adenine methyltransferase (designated pamA). pamA increased expression of fibronectin-binding protein A (fnbA; FnBPA), and inactivation of fnbA eliminated the effect of pamA on abscess virulence without affecting strains lacking pamA. Thus, fnbA is a pamA-specific virulence factor. Mechanistically, pamA was shown to promote biofilm formation in vivo in skin abscesses, a phenotype linked to FnBPAs role in biofilm formation. Collectively, these data reveal a novel mechanism—epigenetic regulation of staphylococcal gene expression—by which phage can regulate virulence to drive adaptive leaps by S. aureus.

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“…Samples were subsequently incubated for 45 min in an Elmasonic S15H ultrasonic bath (Elma, Lomza, Poland) at room temperature. Mass spectrometry identification of peptides present in the aspirated liquid was carried out in the same setting as in Bonar et al [ 64 ].…”

Section: Methodsmentioning

confidence: 99%

Staphylococcal saoABC Operon Codes for a DNA-Binding Protein SaoC Implicated in the Response to Nutrient Deficit

Bukowski

Kosecka-Strojek

Madry

et al. 2022

IJMS

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Whilst a large number of regulatory mechanisms for gene expression have been characterised to date, transcription regulation in bacteria still remains an open subject. In clinically relevant and opportunistic pathogens, such as Staphylococcus aureus, transcription regulation is of great importance for host-pathogen interactions. In our study we investigated an operon, exclusive to staphylococci, that we name saoABC. We showed that SaoC binds to a conserved sequence motif present upstream of the saoC gene, which likely provides a negative feedback loop. We have also demonstrated that S. aureus ΔsaoB and ΔsaoC mutants display altered growth dynamics in non-optimal media; ΔsaoC exhibits decreased intracellular survival in human dermal fibroblasts, whereas ΔsaoB produces an elevated number of persisters, which is also elicited by inducible production of SaoC in ΔsaoBΔsaoC double mutant. Moreover, we have observed changes in the expression of saoABC operon genes during either depletion of the preferential carbon or the amino acid source as well as during acidification. Comparative RNA-Seq of the wild type and ΔsaoC mutant demonstrated that SaoC influences transcription of genes involved in amino acid transport and metabolism, and notably of those coding for virulence factors. Our results suggest compellingly that saoABC operon codes for a DNA-binding protein SaoC, a novel staphylococcal transcription factor, and its antagonist SaoB. We linked SaoC to the response to nutrient deficiency, a stress that has a great impact on host-pathogen interactions. That impact manifests in SaoC influence on persister formation and survival during internalisation to host cells, as well as on the expression of genes of virulence factors that may potentially result in profound alternations in the pathogenic phenotype. Investigation of such novel regulatory mechanisms is crucial for our understanding of the dynamics of interactions between pathogenic bacteria and host cells, particularly in the case of clinically relevant, opportunistic pathogens such as Staphylococcus aureus.

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Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of Virulent and Non-virulent Staphylococcus aureus Strains

Cited by 10 publications

References 70 publications

Prevalence of Antibiotic and Heavy Metal Resistance Determinants and Virulence-Related Genetic Elements in Plasmids of Staphylococcus aureus

Prevalence of Antibiotic and Heavy Metal Resistance Determinants and Virulence-Related Genetic Elements in Plasmids of Staphylococcus aureus

Prophage-encoded methyltransferase drives adaptation of community-acquired methicillin-resistantStaphylococcus aureus

Staphylococcal saoABC Operon Codes for a DNA-Binding Protein SaoC Implicated in the Response to Nutrient Deficit

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