1. Inicio
  2. Publicaciones
  3. Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in Enterococcus faecalis

Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in Enterococcus faecalis

Fecha de publicación: Fecha Ahead of Print:

Autores organización

Autores

  • Khan, A
  • Davlieva, M
  • Miller, WR
  • Diaz, L
  • Cruz, MR
  • Pemberton, O
  • Nguyen, AH
  • Siegel, SD
  • Planet, PJ
  • Narechania, A
  • Latorre, M
  • Rios, R
  • Singh, KV
  • Hung, TT
  • Garsin, DA
  • Tran, TT
  • Shamoo, Y
  • Arias, CA

Grupos de investigación

Resumen

Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecalis, an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the Caenorhabditis elegans model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host-pathogen interactions.

Datos de la publicación

ISSN/ISSNe:
1091-6490, 0027-8424

Proceedings of the National Academy of Sciences of the United States of America  National Academy of Sciences

Tipo:
Article
Páginas:
26925-26932

Citas Recibidas en Web of Science: 53

Citas Recibidas en Scopus: 67

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • antibiotic resistance; Enterococcus faecalis; daptomycin; cell membrane adaptation; antimicrobial peptides

Campos de estudio

Proyectos asociados

Consorcio de resistencia a carbapenems en Klebsiella pneumoniae y otras enterobacteriaceae (CRACKLE): un estudio de cohorte prospectivo y observacional” en su componente de coordinación clínica. En inglés. Consortium on Resistance Against Carbapenems in Klebsiella pneumoniae and Other Enterobacteriaceae (CRACKLE): a Prospective, Observational Cohort Study (CRACKLE II). Componente clínico. Ultimo año. Nuevo título. Red de organismos multiresistentes MDRO “ARLG MDRO SOUTH &CENTRAL AMERICA”

Investigador Principal: JINNETHE CRISTINA REYES MANRIQUE

UEB-2017-456 . 2017

Caracterización del efecto inóculo a cefazolina en Staphylococcus aureus susceptibles a Meticilina (MSSA) causantes de infecciones: implementación de una prueba de detección rápida - Rapid IE - MSSA

Investigador Principal: SANDRA LILIANA RINCON NUÑEZ

UEB-2018-475 . 2018

Dinámicas de colonización e infección por microorganismos multidrogorresistentes en pacientes de hospitales de alta complejidad

Investigador Principal: JINNETHE CRISTINA REYES MANRIQUE

UEB-2018-476 . 2018

ARLG MDRO SOUTH & CENTRAL AMERICA

Investigador Principal: JINNETHE CRISTINA REYES MANRIQUE

2019

Citar la publicación

Compartir la publicación