Complete Genome Sequence of
            <i>Staphylococcus aureus</i>
            Strain JKD6159, a Unique Australian Clone of ST93-IV Community Methicillin-Resistant
            <i>Staphylococcus aureus</i>

Chua, Kyra; Seemann, Torsten; Harrison, Paul F.; Davies, John K.; Coutts, Scott; Chen, Honglei; Häring, Volker; Moore, Robert J.; Howden, Benjamin P; Stinear, Timothy P.

doi:10.1128/jb.00878-10

Cited by 45 publications

(38 citation statements)

References 11 publications

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“…Rigid filtering yielded two nonsynonymous single- (Fig. 4A), which exhibits signatures of an inorganic phosphate (P i ) transporter that is designated pitA in S. aureus strain JKD6159 (41). PitA is predicted to contain seven transmembrane helices, with the A57V mutation being located in the second helix.…”

Section: Resultsmentioning

confidence: 99%

A Novel Point Mutation Promotes Growth Phase-Dependent Daptomycin Tolerance in Staphylococcus aureus

Mechler

Herbig

Paprotka

et al. 2015

Antimicrob Agents Chemother

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Recalcitrance of genetically susceptible bacteria to antibiotic killing is a hallmark of bacterial drug tolerance. This phenomenon is prevalent in biofilms, persisters, and also planktonic cells and is associated with chronic or relapsing infections with pathogens such as Staphylococcus aureus. Here we report the in vitro evolution of an S. aureus strain that exhibits a high degree of nonsusceptibility to daptomycin as a result of cyclic challenges with bactericidal concentrations of the drug. This phenotype was attributed to stationary growth phase-dependent drug tolerance and was clearly distinguished from resistance. The underlying genetic basis was revealed to be an adaptive point mutation in the putative inorganic phosphate (P i ) transporter gene pitA. Drug tolerance caused by this allele, termed pitA6, was abrogated when the upstream gene pitR was inactivated. Enhanced tolerance toward daptomycin, as well as the acyldepsipeptide antibiotic ADEP4 and various combinations of other drugs, was accompanied by elevated intracellular concentrations of P i and polyphosphate, which may reversibly interfere with critical cellular functions. The evolved strain displayed increased rates of survival within human endothelial cells, demonstrating the correlation of intracellular persistence and drug tolerance. These findings will be useful for further investigations of S. aureus drug tolerance, toward the development of additional antipersister compounds and strategies.

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Section: Resultsmentioning

confidence: 99%

A Novel Point Mutation Promotes Growth Phase-Dependent Daptomycin Tolerance in Staphylococcus aureus

Mechler

Herbig

Paprotka

et al. 2015

Antimicrob Agents Chemother

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“…The sequencing of the whole genome of multiple S. aureus strains, 123 followed by those of methicillin-resistant 124,125 and vancomycin-intermediate 126 and epidemic 127 strains undoubtedly marked a significant step forward. The subsequent development of bioinformatics to manipulate and analyze these data has facilitated high-throughput genomic, transcriptomic and proteomic analyses of microbial growth and pathogenesis.…”

Section: Vaccinesmentioning

confidence: 99%

Staphylococcus aureusbiofilms

et al. 2011

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“…Based on its genome sequence, ST93, like USA300, contains α-hemolysin, PVL and PSM-α (Chua et al, 2010) gain, no overt novel virulence determinant has been identified in ST93 that could easily explain its high virulence capacity, suggesting the contribution of altered gene expression or subtle genetic alterations in the core genome. Furthermore, it is tempting to speculate that, while ST93 is highly virulent, the lack of an obvious fitness factor, such as the ACME- arcA - speG system in USA300, might account for its relatively limited geographic distribution.…”

Section: Community-associated Mrsamentioning

confidence: 99%

Evolution of community- and healthcare-associated methicillin-resistant Staphylococcus aureus

Uhlemann

Otto

Lowy

et al. 2014

Infection, Genetics and Evolution

164

166

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Staphylococcus aureus is a prominent cause of human infections globally. The high prevalence of infections is compounded by antibiotic resistance—a significant problem for treatment. Methicillin-resistant S. aureus (MRSA) is endemic in hospitals and healthcare facilities worldwide, and is an increasingly common cause of community-associated bacterial infections in industrialized countries. Although much focus is placed on the role of S. aureus as a human pathogen, it is in fact a human commensal organism that has had a relatively long coexistence with the human host. Many S. aureus infections can be explained by host susceptibility or other predisposing risk factors. On the other hand, the emergence/re-emergence of successful S. aureus clones (referred to as epidemic waves) suggests a rapid bacterial adaption and evolution, which includes the emergence of antibiotic resistance and increased virulence and/or transmissibility. It is within this context that we review our understanding of selected S. aureus epidemic waves, and highlight the use of genome sequencing as a means to better understand the evolution of each lineage.

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Complete Genome Sequence of Staphylococcus aureus Strain JKD6159, a Unique Australian Clone of ST93-IV Community Methicillin-Resistant Staphylococcus aureus

Cited by 45 publications

References 11 publications

A Novel Point Mutation Promotes Growth Phase-Dependent Daptomycin Tolerance in Staphylococcus aureus

A Novel Point Mutation Promotes Growth Phase-Dependent Daptomycin Tolerance in Staphylococcus aureus

Staphylococcus aureusbiofilms

Evolution of community- and healthcare-associated methicillin-resistant Staphylococcus aureus

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