Coagulase-negative staphylococci (CoNS) are important nosocomial pathogens and the leading cause of sepsis. The second most frequently implicated species, afterStaphylococcus epidermidis, isStaphylococcus haemolyticus. However, we have a significant lack of knowledge about what causes virulence ofS. haemolyticus, as virulence factors of this pathogen have remained virtually unexplored. In contrast to the aggressive pathogenStaphylococcus aureus, toxin production has traditionally not been associated with CoNS. Recent findings have suggested that phenol-soluble modulins (PSMs), amphipathic peptide toxins with broad cytolytic activity, are widespread in staphylococci, but there has been no systematic assessment of PSM production in CoNS other thanS. epidermidis. Here, we identified, purified, and characterized PSMs ofS. haemolyticus. We found three PSMs of the β-type, which correspond to peptides that before were described to have anti-gonococcal activity. We also detected an α-type PSM that has not previously been described. Furthermore, we confirmed thatS. haemolyticusdoes not produce a δ-toxin, as results from genome sequencing had indicated. All fourS. haemolyticusPSMs had strong pro-inflammatory activity, promoting neutrophil chemotaxis. Notably, we identified in particular the novel α-type PSM,S. haemolyticusPSMα, as a potent hemolysin and leukocidin. For the first time, our study describes toxins of this important staphylococcal pathogen with the potential to have a significant impact on virulence during blood infection and sepsis.
