Group IIA-Secreted Phospholipase A2in Human Serum Kills Commensal but Not ClinicalEnterococcus faeciumIsolates
ABSTRACTHuman innate immunity employs cellular and humoral mechanisms to facilitate rapid killing of invading bacteria. The direct killing of bacteria by human serum is attributed mainly to the activity of the complement system, which forms pores in Gram-negative bacteria. Although Gram-positive bacteria are considered resistant to killing by serum, we uncover here that normal human serum effectively killsEnterococcus faecium. Comparison of a well-characterized collection of commensal and clinicalE. faeciumisolates revealed that human serum specifically kills commensalE. faeciumstrains isolated from normal gut microbiota but not clinical isolates. Inhibitor studies show that the human group IIA secreted phospholipase A2 (hGIIA), but not complement, is responsible for killing of commensalE. faeciumstrains in human normal serum. This is remarkable since the hGIIA concentration in “noninflamed” serum was considered too low to be bactericidal against Gram-positive bacteria. Mechanistic studies showed that serum hGIIA specifically causes permeabilization of commensalE. faeciummembranes. Altogether, we find that a normal concentration of hGIIA in serum effectively kills commensalE. faeciumand that resistance of clinicalE. faeciumto hGIIA could have contributed to the ability of these strains to become opportunistic pathogens in hospitalized patients.