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Infect Immun. 2018 Jul 23;86(8). pii: e00180-18. doi: 10.1128/IAI.00180-18. Print 2018 Aug.

Group IIA-Secreted Phospholipase A2 in Human Serum Kills Commensal but Not Clinical Enterococcus faecium Isolates.

Author information

1
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands f.paganelli@umcutrecht.nl.
2
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
3
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
4
Université Côte d'Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.

Abstract

Human 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 kills Enterococcus faecium Comparison of a well-characterized collection of commensal and clinical E. faecium isolates revealed that human serum specifically kills commensal E. faecium strains 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 commensal E. faecium strains 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 commensal E. faecium membranes. Altogether, we find that a normal concentration of hGIIA in serum effectively kills commensal E. faecium and that resistance of clinical E. faecium to hGIIA could have contributed to the ability of these strains to become opportunistic pathogens in hospitalized patients.

KEYWORDS:

Enterococcus faecium; commensals; group IIA secreted phospholipase A2; innate immune system; pathogens

PMID:
29784864
PMCID:
PMC6056852
[Available on 2019-01-23]
DOI:
10.1128/IAI.00180-18

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