Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in <i>Enterococcus faecalis</i>
Journal
The Journal of Infectious Diseases
ISSN
0022-1899
Date Issued
2024
Author(s)
William R Miller
April Nguyen
Kavindra V Singh
Samie Rizvi
Ayesha Khan
Sam G Erickson
Stephanie L Egge
Melissa Cruz
An Q Dinh
Philip C Thornton
Rutan Zhang
Libin Xu
Danielle A Garsin
Yousif Shamoo
Cesar A Arias
Type
journal-article
Abstract
<jats:title>Abstract</jats:title>
<jats:p>Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.</jats:p>
<jats:p>Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.</jats:p>
Cite this document
Miller, W. R., Nguyen, A., Singh, K. V., Rizvi, S., Khan, A., Erickson, S. G., Egge, S. L., Cruz, M., Dinh, A. Q., Diaz, L., Thornton, P. C., Zhang, R., Xu, L., Garsin, D. A., Shamoo, Y., & Arias, C. A. (2024). Membrane lipids augment cell envelope stress signaling via the madrs system to defend against antimicrobial peptides and antibiotics in enterococcus faecalis. The Journal of Infectious Diseases, jiae173. https://doi.org/10.1093/infdis/jiae173
Subjects
enterococcus faecalis
;
daptomycin
;
antimicrobial peptides
;
membrane lipids
;
cell envelope stress response