ORCID Profile
0000-0001-5971-1163
Current Organisation
University of Warsaw
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Publisher: American Society for Microbiology
Date: 07-11-2018
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) poses a substantial threat to human health worldwide and evolves rapidly by acquiring mobile genetic elements, such as plasmids. Here we investigate how the copB - mco copper hypertolerance operon carried on a mobile genetic element contributes to the virulence potential of clinical isolates of MRSA. Copper is a key component of innate immune bactericidal defenses. Here we show that copper hypertolerance genes enhance the survival of S. aureus inside primed macrophages and in whole human blood. The copB and mco genes are carried by clinical isolates responsible for invasive infections across Europe, and more broadly among three successful clonal lineages of S. aureus . Our findings show that a gain of copper hypertolerance genes increases the resistance of MRSA to phagocytic killing by host immune cells and imply that acquisition of this mobile genetic element can contribute to the success of MRSA.
Publisher: Cold Spring Harbor Laboratory
Date: 08-03-2018
DOI: 10.1101/279000
Abstract: Pathogens are exposed to toxic levels of copper during infection and copper tolerance may be a general virulence mechanism used by bacteria to resist host defences. In support of this, inactivation of copper-exporter genes has been found to reduce the virulence of bacterial pathogens in vivo . Here we investigate the role of copper-hypertolerance in methicillin resistant Staphylococcus aureus . We show that a copper-hypertolerance locus ( copB-mco ), carried on a mobile genetic element, is prevalent in a collection of invasive S. aureus strains and more widely among clonal complex 22, 30 and 398 strains. The copB and mco genes encode a copper efflux pump and a multicopper oxidase, respectively. Isogenic mutants lacking copB or mco had impaired growth in subinhibitory concentrations of copper. Transfer of a copB-mco encoding plasmid to a naive clinical isolate resulted in a gain of copper hypertolerance and enhanced bacterial survival inside primed macrophages. The copB and mco genes were upregulated within infected macrophages and their expression was dependent on the copper sensitive operon repressor CsoR. Isogenic copB and mco mutants were impaired in their ability to persist intracellularly in macrophages and were less resistant to phagocytic killing in human blood than the parent strain. The importance of copper-regulated genes in resistance to phagocytic killing was further elaborated using mutants expressing a copper-insensitive variant of CsoR. Our findings suggest that the gain of mobile genetic elements carrying copper-hypertolerance genes contributes to the evolution of virulent strains of S. aureus , better equipped to resist killing by host immune cells.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.JHIN.2017.02.008
Abstract: Staphylococcus aureus is a leading cause of healthcare-associated infections. The ability of S. aureus to attach and subsequently accumulate on the surfaces of implanted medical devices and in host tissues makes infections caused by this pathogen difficult to treat. Current treatments have been shown to have limited effect on surface-associated S. aureus, and may be enhanced by the addition of a dispersal agent. This study assessed the enzymatic agents dispersin B, lysostaphin, alpha amylase, V8 protease and serrapeptase, alone and in combination with vancomycin and rif icin, against biofilms formed by meticillin-resistant and -susceptible strains of S. aureus. The efficacy of both antibiotics was enhanced when combined with any of the dispersal agents. Lysostaphin and serrapeptase were the most effective dispersal agents against all strains tested. These data indicate that combinations of biofilm dispersal agents and antibiotics may extend the therapeutic options for the treatment of S. aureus biofilm-associated infections.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Ireland
No related grants have been discovered for Marta Zapotoczna.