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 mainly attributed to the activity of the complement system that forms pores in Gram-negative bacteria. Although Gram-positive bacteria are considered resistant to serum killing, we here uncover 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 hGIIA concentrations in ‘non-inflamed’ serum were 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 serum concentration of hGIIA effectively kills commensalE. faeciumand that hGIIA resistance of clinicalE. faeciumcould have contributed to the ability of these strains to become opportunistic pathogens in hospitalized patients.ImportanceHuman normal serum contains antimicrobial components that effective kill invading Gram-negative bacteria. Although Gram-positive bacteria are generally considered resistant to serum killing, here we show that normal human effectively kills the Gram-positiveEnterococcus faeciumstrains that live as commensals in the gut of humans. In contrast, clinicalE. faeciumstrains that are responsible for opportunistic infections in debilitated patients are resistant against human serum. The key factor in serum responsible for killing is group IIA secreted phospholipase A2 (hGIIA) that effectively destabilizes commensalE. faeciummembranes. We believe that hGIIA resistance by clinicalE. faeciumcould have contributed to the ability of these strains to cause opportunistic infections in hospitalized patients. Altogether, understanding mechanisms of immune defense and bacterial resistance could aid in further development of novel anti-infective strategies against medically important multidrug resistant Gram-positive pathogens.