Enterococcus faecium secreted antigen A generates muropeptides to enhance host immunity and limit bacterial pathogenesis

被引：70

作者：

Kim, Byungchul ^{[1
]}

Wang, Yen-Chih ^{[1
]}

Hespen, Charles W. ^{[1
]}

Espinosa, Juliel ^{[1
]}

Salje, Jeanne ^{[2
]}

Rangan, Kavita J. ^{[1
]}

Oren, Deena A. ^{[3
]}

Kang, Jin Young ^{[4
]}

Pedicord, Virginia A. ^{[1
,5
]}

Hang, Howard C. ^{[1
]}

机构：

[1] Rockefeller Univ, Lab Chem Biol & Microbial Pathogenesis, 1230 York Ave, New York, NY 10021 USA

[2] Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England

[3] Rockefeller Univ, Struct Biol Resource Ctr, 1230 York Ave, New York, NY 10021 USA

[4] Rockefeller Univ, Lab Mol Biophys, 1230 York Ave, New York, NY 10021 USA

[5] Univ Cambridge, Cambridge Inst Therapeut Immunol & Infect Dis, Cambridge, England

来源：

ELIFE | 2019年 / 8卷

关键词：

ACCURATE DOCKING; PEPTIDOGLYCAN; NOD2; COLONIZATION; RECOGNITION; RESISTANCE; COMMENSAL; PROTEINS; MODEL; GLIDE;

D O I：

10.7554/eLife.45343

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We discovered that Enterococcus faecium (E. faecium), a ubiquitous commensal bacterium, and its secreted peptidoglycan hydrolase (SagA) were sufficient to enhance intestinal barrier function and pathogen tolerance, but the precise biochemical mechanism was unknown. Here we show E. faecium has unique peptidoglycan composition and remodeling activity through SagA, which generates smaller muropeptides that more effectively activates nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in mammalian cells. Our structural and biochemical studies show that SagA is a NlpC/p60-endopeptidase that preferentially hydrolyzes crosslinked Lys-type peptidoglycan fragments. SagA secretion and NlpC/p60-endopeptidase activity was required for enhancing probiotic bacteria activity against Clostridium difficile pathogenesis in vivo. Our results demonstrate that the peptidoglycan composition and hydrolase activity of specific microbiota species can activate host immune pathways and enhance tolerance to pathogens.

引用

页数：25

共 66 条

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