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 by 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. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally “unintended” interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches.

Staphylococcus aureus and Coagulase-Negative Staphylococci in Bacteraemia: The Epidemiology, Predisposing Factors, Pathogenicity and Antimicrobial Resistance

“…Staphylococcus saprophyticus, Staphylococcus [14]. The common CoNS species isolated clinically and often considered for its virulence and pathogenicity is Staphylococcus epidermidis [5,15,16].…”

The evolutionary logic of sepsis

“…Several bacteria involved in sepsis produce neurotoxins or enterotoxins (Popoff and Poulain, 2010), and some of these toxins appear to contribute actively to the induction of sepsis (Choi et al, 2016;Qin et al, 2017). The classical hypothesis of sepsis induction implies that these molecules have evolved for functions unrelated to pathogenesis, and their toxic action is a non-adaptive, accidental by-product.…”

Methicillin Resistance and Biofilm Formation of Staphylococcus epidermidis in Blood Culture Isolates from Children under Five: A Multicenter Study in Nigeria

“…The frequent coagulase-negative Staphylococcus isolated in bloodstream infection is S. epidermidis [8,9]. It can colonize and adhere to implanted medical devices and venous catheters through its ability to develop an organized structure of micro-colonies or multicellular structures known as biofilm [6].…”