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Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis

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dc.contributor.authorMiller, William
dc.contributor.authorNguyen, April
dc.contributor.authorSingh, Kavindra
dc.contributor.authorRizvi, Samie
dc.contributor.authorKhan, Ayesha
dc.contributor.authorErickson, Sam
dc.contributor.authorEgge, Stephanie
dc.contributor.authorCruz, Melissa
dc.contributor.authorDinh, An
dc.contributor.authorDiaz, Lorena
dc.contributor.authorThornton, Philip
dc.contributor.authorZhang, Rutan
dc.contributor.authorXu, Libin
dc.contributor.authorGarsin, Danielle
dc.contributor.authorShamoo, Yousif
dc.contributor.authorArias, Cesar
dc.date.accessioned2026-08-10T17:04:58Z
dc.date.available2026-08-10T17:04:58Z
dc.date.issued2025
dc.description.abstractEnterococci 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.
dc.description.versionVersión Publicada
dc.identifier.citationMiller WR, Nguyen A, Singh KV, Rizvi S, Khan A, Erickson SG, Egge SL, Cruz M, Dinh AQ, Diaz L, Thornton PC, Zhang R, Xu L, Garsin DA, Shamoo Y, Arias CA. Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis. J Infect Dis. 2025 Feb 20;231(2):307-317. doi: 10.1093/infdis/jiae173
dc.identifier.doihttps://doi.org/10.1093/infdis/jiae173
dc.identifier.urihttps://hdl.handle.net/11447/10984
dc.language.isoen
dc.subjectEnterococcus faecalis
dc.subjectantimicrobial peptides
dc.subjectcell envelope stress response
dc.subjectdaptomycin
dc.subjectmembrane lipids
dc.titleMembrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceThe Journal of infectious diseases
dspace.entity.typePublication

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