Faculty Collaboration Database

Convergence of PASTA Kinase and Two-Component Signaling in Response to Cell Wall Stress in Enterococcus faecalis. J Bacteriol 2018 Jun 15;200(12)

Date

04/11/2018

Pubmed ID

29632091

Pubmed Central ID

PMC5971478

DOI

10.1128/JB.00086-18

Scopus ID

2-s2.0-85047458915 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

Two common signal transduction mechanisms used by bacteria to sense and respond to changing environments are two-component systems (TCSs) and eukaryote-like Ser/Thr kinases and phosphatases (eSTK/Ps). Enterococcus faecalis is a Gram-positive bacterium and a serious opportunistic pathogen that relies on both a TCS and an eSTK/P pathway for intrinsic resistance to cell wall-targeting antibiotics. The TCS consists of a histidine kinase (CroS) and a response regulator (CroR) that become activated upon exposure of cells to cell wall-targeting antibiotics, leading to a modulation of gene expression. The eSTK/P pathway consists of a transmembrane kinase (IreK) and its cognate phosphatase (IreP), which act antagonistically to mediate antibiotic resistance through an unknown mechanism. Because both CroS/R and IreK/P contribute to enterococcal resistance toward cell wall-targeting antibiotics, we hypothesized that these signaling systems are intertwined. To test this hypothesis, we analyzed CroR phosphorylation and CroS/R-dependent gene expression to probe the influence of IreK and IreP on CroS/R signaling. In addition, we analyzed the phosphorylation state of CroS, which revealed the IreK-dependent phosphorylation of a Thr residue important for CroS function. Our results are consistent with a model in which IreK positively influences CroR-dependent gene expression through the phosphorylation of CroS to promote antimicrobial resistance in E. faecalisIMPORTANCE Two-component signaling systems (TCSs) and eukaryote-like Ser/Thr kinases (eSTKs) are used by bacteria to sense and adapt to changing environments. Understanding how these pathways are regulated to promote bacterial survival is critical for a more complete understanding of bacterial stress responses and physiology. The opportunistic pathogen Enterococcus faecalis relies on both a TCS (CroS/R) and an eSTK (IreK) for intrinsic resistance to cell wall-targeting antibiotics. We probed the relationship between CroS/R and IreK, revealing the convergence of IreK and the sensor kinase CroS to enhance signaling through CroS/R and increase antimicrobial resistance in E. faecalis This newly described example of eSTK/TCS convergence adds to our understanding of the signaling networks mediating antimicrobial resistance in E. faecalis.

Author List

Kellogg SL, Kristich CJ

Author

Christopher J. Kristich PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anti-Bacterial Agents
Bacterial Proteins
Cell Wall
Enterococcus faecalis
Gene Expression Regulation, Bacterial
Histidine Kinase
Phosphorylation
Signal Transduction