Toxin mediates sepsis caused by methicillin-resistant Staphylococcus epidermidis

ABSTRACT: Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused my methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. While toxins have never been clearly indicated in CNS infections, our study shows that an important type of infection caused by the predominant CNS species, S. epidermidis, is mediated to a large extent by a toxin. Of note, these findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches. We used microarrays to detail the global gene expression between S. epidermidis strain Rp62A and S. epidermidis strain Rp62A isogenic Δpsm-mec deletion mutants

ORGANISM(S): Rickettsia rickettsii Staphylococcus epidermidis RP62A Staphylococcus epidermidis ATCC 12228 Coxiella burnetii RSA 493 Granulibacter bethesdensis Staphylococcus epidermidis Coxiella burnetii Chlamydia muridarum Chlamydia trachomatis D/UW-3/CX Staphylococcus haemolyticus JCSC1435 Borreliella burgdorferi B31 Chlamydia pneumoniae AR39 Staphylococcus aureus subsp. aureus MW2 Chlamydia caviae GPIC

PROVIDER: GSE85265 | GEO | 2017/01/06

SECONDARY ACCESSION(S): PRJNA337973

REPOSITORIES: GEO