The Library
A bacterial inflammation sensor regulates c-di-GMP signaling, adhesion, and biofilm formation
Tools
Perkins, Arden, Tudorica, Dan A., Teixeira, Raphael D., Schirmer, Tilman, Zumwalt, Lindsay, Ogba, O. Maduka, Cassidy, C. Keith, Stansfeld, Phillip J., Guillemin, Karen and Cooper, Vaughn S. (2021) A bacterial inflammation sensor regulates c-di-GMP signaling, adhesion, and biofilm formation. mBio, 12 (3). e00173-21. doi:10.1128/mBio.00173-21 ISSN 2150-7511.
|
PDF
WRAP-bacterial-inflammation-Sensor-regulates-c-di-GMP-signalin-adhesion-biofilm-formation-Stansfield-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (7Mb) | Preview |
Official URL: http://dx.doi.org/10.1128/mBio.00173-21
Abstract
Bacteria that colonize animals must overcome, or coexist, with the reactive oxygen species products of inflammation, a front-line defense of innate immunity. Among these is the neutrophilic oxidant bleach, hypochlorous acid (HOCl), a potent antimicrobial that plays a primary role in killing bacteria through nonspecific oxidation of proteins, lipids, and DNA. Here, we report that in response to increasing HOCl levels, Escherichia coli regulates biofilm production via activation of the diguanylate cyclase DgcZ. We identify the mechanism of DgcZ sensing of HOCl to be direct oxidation of its regulatory chemoreceptor zinc-binding (CZB) domain. Dissection of CZB signal transduction reveals that oxidation of the conserved zinc-binding cysteine controls CZB Zn2+ occupancy, which in turn regulates the catalysis of c-di-GMP by the associated GGDEF domain. We find DgcZ-dependent biofilm formation and HOCl sensing to be regulated in vivo by the conserved zinc-coordinating cysteine. Additionally, point mutants that mimic oxidized CZB states increase total biofilm. A survey of bacterial genomes reveals that many pathogenic bacteria that manipulate host inflammation as part of their colonization strategy possess CZB-regulated diguanylate cyclases and chemoreceptors. Our findings suggest that CZB domains are zinc-sensitive regulators that allow host-associated bacteria to perceive host inflammation through reactivity with HOCl.
Item Type: | Journal Article | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RB Pathology |
||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Oxidation-reduction reaction, Clinical biochemistry, Cellular signal transduction, Chemoreceptors, Biofilms | ||||||||||||||||||
Journal or Publication Title: | mBio | ||||||||||||||||||
Publisher: | American Society for Microbiology | ||||||||||||||||||
ISSN: | 2150-7511 | ||||||||||||||||||
Official Date: | 22 June 2021 | ||||||||||||||||||
Dates: |
|
||||||||||||||||||
Volume: | 12 | ||||||||||||||||||
Number: | 3 | ||||||||||||||||||
Article Number: | e00173-21 | ||||||||||||||||||
DOI: | 10.1128/mBio.00173-21 | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
Date of first compliant deposit: | 8 September 2021 | ||||||||||||||||||
Date of first compliant Open Access: | 10 September 2021 | ||||||||||||||||||
RIOXX Funder/Project Grant: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year