Secreted Proteases Control the Timing of Aggregative Community Formation in Vibrio cholerae.

TitleSecreted Proteases Control the Timing of Aggregative Community Formation in Vibrio cholerae.
Publication TypeJournal Article
Year of Publication2021
AuthorsJemielita, M, Mashruwala, AA, Valastyan, JS, Wingreen, NS, Bassler, BL
JournalmBio
Volume12
Issue6
Paginatione0151821
Date Published2021 12 21
ISSN2150-7511
KeywordsBiofilms, Cholera, Humans, Metalloendopeptidases, Operon, Peptide Hydrolases, Quorum Sensing, Vibrio cholerae
Abstract

<p>Bacteria orchestrate collective behaviors using the cell-cell communication process called quorum sensing (QS). QS relies on the synthesis, release, and group-wide detection of small molecules called autoinducers. In Vibrio cholerae, a multicellular community aggregation program occurs in liquid, during the stationary phase, and in the high-cell-density QS state. Here, we demonstrate that this aggregation program consists of two subprograms. In one subprogram, which we call void formation, structures form that contain few cells but provide a scaffold within which cells can embed. The other subprogram relies on flagellar machinery and enables cells to enter voids. A genetic screen for factors contributing to void formation, coupled with companion molecular analyses, showed that four extracellular proteases, Vca0812, Vca0813, HapA, and PrtV, control the onset timing of both void formation and aggregation; moreover, proteolytic activity is required. These proteases, or their downstream products, can be shared between void-producing and non-void-forming cells and can elicit aggregation in a normally nonaggregating V. cholerae strain. Employing multiple proteases to control void formation and aggregation timing could provide a redundant and irreversible path to commitment to this community lifestyle. Bacteria can work as collectives to form multicellular communities. Vibrio cholerae, the bacterium that causes the disease cholera in humans, forms aggregated communities in liquid. Aggregate formation relies on a chemical communication process called quorum sensing. Here, we show that, beyond overarching control by quorum sensing, there are two aggregation subprograms. One subprogram, which we call void formation, creates a scaffold within which cells can embed. The second subprogram, which allows bacteria to enter the scaffold, requires motility. We discovered that four extracellular proteases control the timing of both void formation and aggregation. We argue that, by using redundant proteases, V. cholerae ensures the reliable execution of this community formation process. These findings may provide insight into how V. cholerae persists in the marine environment or colonizes the human host, as both lifestyles are central to the spread of the disease cholera.</p>

DOI10.1128/mBio.01518-21
Alternate JournalmBio
PubMed ID34809464
PubMed Central IDPMC8609355
Grant ListK99 GM138764 / GM / NIGMS NIH HHS / United States
R01 GM082938 / GM / NIGMS NIH HHS / United States
R37 GM065859 / GM / NIGMS NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States