The Phosphatase Bph and Peptidyl-Prolyl Isomerase PrsA Are Required for Gelatinase Expression and Activity in Enterococcus faecalis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Enterococcus faecalis is a common commensal bacterium in the gastrointestinal tract as well as a frequent nosocomial pathogen. The secreted metalloprotease gelatinase (GelE) is an important E. faecalis virulence factor that contributes to numerous cellular activities, such as autolysis, biofilm formation, and biofilm-associated antibiotic resistance. Expression of gelE has been extensively studied and is regulated by the Fsr quorum sensing system. Here, we identify two additional factors regulating gelatinase expression and activity in E. faecalis OG1RF. The Bph phosphatase is required for expression of gelE in an Fsr-dependent manner. Additionally, the membrane-anchored protein foldase PrsA is required for GelE activity, but not fsr or gelE gene expression. Disrupting prsA also leads to increased antibiotic sensitivity in biofilms independent of the loss of GelE activity. Together, our results expand the model for gelatinase production in E. faecalis, which has important implications for fundamental studies of GelE function in Enterococcus and also E. faecalis pathogenesis. IMPORTANCE In Enterococcus faecalis, gelatinase (GelE) is a virulence factor that is also important for biofilm formation and interactions with other microbes as well as the host immune system. The long-standing model for GelE production is that the Fsr quorum sensing system positively regulates expression of gelE. Here, we update that model by identifying two additional factors that contribute to gelatinase production. The biofilm-associated Bph phosphatase regulates the expression of gelE through Fsr, and the peptidyl-prolyl isomerase PrsA is required for production of active GelE through an Fsr-independent mechanism. This provides important insight into how regulatory networks outside of the fsr locus coordinate expression of gelatinase.

Original languageEnglish (US)
JournalJournal of bacteriology
Volume204
Issue number7
DOIs
StatePublished - Jul 2022

Bibliographical note

Funding Information:
We thank Lynn Hancock, Marta Perego, and Dawn Manias for providing plasmid constructs. We acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota (http://www.msi.umn.edu) and the University of Minnesota Genomics Center (https://genomics.umn.edu/) for providing resources that contributed to the results reported here. This work was supported by National Institutes of Health grants R35GM118079 and R01AI122742 to G.M.D., 1K99AI151080 to J.L.E.W., and the National Center for Advancing Translational Sciences grant UL1TR002494. E.B.R. was supported by the University of Minnesota Undergraduate Research Opportunities Program (UROP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.

Funding Information:
We thank Lynn Hancock, Marta Perego, and Dawn Manias for providing plasmid constructs. We acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota (http://www.msi.umn.edu) and the University of Minnesota Genomics Center (https://genomics.umn.edu/) for providing resources that contributed to the results reported here. This work was supported by National Institutes of Health grants R35GM118079 and R01AI122742 to G.M.D., 1K99AI151080 to J.L.E.W., and the National Center for Advancing Translational Sciences grant UL1TR002494. E.B.R. was supported by the University of Minnesota Undergraduate Research Opportunities Program (UROP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences.

Publisher Copyright:
© 2022 American Society for Microbiology. All Rights Reserved.

Keywords

  • Biofilms
  • Enterococcus
  • gelatinase
  • quorum sensing

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

Fingerprint

Dive into the research topics of 'The Phosphatase Bph and Peptidyl-Prolyl Isomerase PrsA Are Required for Gelatinase Expression and Activity in Enterococcus faecalis'. Together they form a unique fingerprint.

Cite this