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TitleSecreted antigen A peptidoglycan hydrolase is essential for cell separation and priming of immune checkpoint inhibitor therapy.
Journal, issue, pagesElife, Vol. 13, Year 2024
Publish dateJun 10, 2024
AuthorsSteven Klupt / Kyong Tkhe Fam / Xing Zhang / Pavan Kumar Chodisetti / Abeera Mehmood / Tumara Boyd / Danielle Grotjahn / Donghyun Park / Howard C Hang /
PubMed Abstract is a microbiota species in humans that can modulate host immunity (Griffin and Hang, 2022), but has also acquired antibiotic resistance and is a major cause of hospital-associated infections (Van ... is a microbiota species in humans that can modulate host immunity (Griffin and Hang, 2022), but has also acquired antibiotic resistance and is a major cause of hospital-associated infections (Van Tyne and Gilmore, 2014). Notably, diverse strains of produce SagA, a highly conserved peptidoglycan hydrolase that is sufficient to promote intestinal immunity (Rangan et al., 2016; Pedicord et al., 2016; Kim et al., 2019) and immune checkpoint inhibitor antitumor activity (Griffin et al., 2021). However, the functions of SagA in were unknown. Here, we report that deletion of impaired growth and resulted in bulged and clustered enterococci due to defective peptidoglycan cleavage and cell separation. Moreover, Δ showed increased antibiotic sensitivity, yielded lower levels of active muropeptides, displayed reduced activation of the peptidoglycan pattern-recognition receptor NOD2, and failed to promote cancer immunotherapy. Importantly, the plasmid-based expression of SagA, but not its catalytically inactive mutant, restored Δ growth, production of active muropeptides, and NOD2 activation. SagA is, therefore, essential for growth, stress resistance, and activation of host immunity.
External linksElife / PubMed:38857064 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-42074: Representative tomogram of Enterococcus faecium WT Com15
Method: EM (tomography)

EMDB-42086: Representative tomogram of Enterococcus faecium SagA complementation strain
Method: EM (tomography)

EMDB-42087: Representative tomogram of Enterococcus faecium SagA deletion strain
Method: EM (tomography)

Source
  • Enterococcus faecium (bacteria)

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