A Bacterial Inflammation Sensor Regulates c-di-GMP Signaling, Adhesion, and Biofilm Formation

Perkins, Arden and Tudorica, Dan A. and Teixeira, Raphael D. and Schirmer, Tilman and Zumwalt, Lindsay and Ogba, O. Maduka and Cassidy, C. Keith and Stansfeld, Phillip J. and Guillemin, Karen. (2021) A Bacterial Inflammation Sensor Regulates c-di-GMP Signaling, Adhesion, and Biofilm Formation. mBio, 12 (3). e0017321.

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Official URL: https://edoc.unibas.ch/84045/

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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 Zn; 2+; 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.; IMPORTANCE; Immune cells are well equipped to eliminate invading bacteria, and one of their primary tools is the synthesis of bleach, hypochlorous acid (HOCl), the same chemical used as a household disinfectant. In this work, we present findings showing that many host-associated bacteria possess a bleach-sensing protein that allows them to adapt to the presence of this chemical in their environment. We find that the bacterium Escherichia coli responds to bleach by hunkering down and producing a sticky matrix known as biofilm, which helps it aggregate and adhere to surfaces. This behavior may play an important role in pathogenicity for E. coli and other bacteria, as it allows the bacteria to detect and adapt to the weapons of the host immune system.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Schirmer)
UniBasel Contributors:Schirmer, Tilman and Dias Teixeira, Raphael
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Microbiology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Feb 2022 18:45
Deposited On:31 Aug 2021 14:01

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