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IreK-Mediated, Cell Wall-Protective Phosphorylation in Enterococcus faecalis. J Proteome Res 2021 Nov 05;20(11):5131-5144

Date

10/22/2021

Pubmed ID

34672600

Pubmed Central ID

PMC10037947

DOI

10.1021/acs.jproteome.1c00635

Scopus ID

2-s2.0-85118785739 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Enterococcus faecalis is a Gram-positive bacterium that is a major cause of hospital-acquired infections due, in part, to its intrinsic resistance to cell wall-active antimicrobials. One critical determinant of this resistance is the transmembrane kinase IreK, which belongs to the penicillin-binding protein and serine/threonine kinase-associated kinase family of bacterial signaling proteins involved with the regulation of cell wall homeostasis. The activity of IreK is enhanced in response to cell wall stress, but direct substrates of IreK phosphorylation, leading to antimicrobial resistance, are largely unknown. To better understand stress-modulated phosphorylation events contributing to antimicrobial resistance, wild type E. faecalis cells treated with cell wall-active antimicrobials, chlorhexidine or ceftriaxone, were examined via phosphoproteomics. Among the most prominent changes was increased phosphorylation of divisome components after both treatments, suggesting that E. faecalis modulates cell division in response to cell wall stress. Phosphorylation mediated by IreK was then determined via a similar analysis with a E. faecalis ΔireK mutant strain, revealing potential IreK substrates involved with the regulation of peptidoglycan biosynthesis and within the E. faecalis CroS/R two-component system, another signal transduction pathway that promotes antimicrobial resistance. These results reveal critical insights into the biological functions of IreK.

Author List

Iannetta AA, Minton NE, Uitenbroek AA, Little JL, Stanton CR, Kristich CJ, Hicks LM

Authors

Christopher J. Kristich PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Nicole E. VanZeeland Postdoctoral Fellow in the Pathology 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
Microbial Sensitivity Tests
Phosphorylation