Project Details
Projekt
A pseudogene affords quorum sensing-mediated phage defense in Vibrio cholerae
Applicant
Professor Dr. Kai Papenfort
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 464459808
Bacteriophages, commonly called phages, are viruses that infect bacteria and are acknowledged as the most abundant biological entities on Earth. The interaction of phages and bacteria plays a pivotal role in shaping microbial communities, influencing bacterial evolution, and contributing to the ecological balance of various environments. The ongoing arms race between phages and bacteria is a biological struggle for survival where bacteria develop defense mechanisms to resist phage infections, while phages continuously evolve strategies to evade bacterial defenses. Over the recent years, numerous novel anti-phage systems have emerged, often found clustered within genomic islands known as defense islands. In contrast, limited knowledge exists regarding anti-phage genes outside defense islands and their contribution to the bacterial anti-phage arsenal have remained unclear. This project seeks to address this gap by investigating the molecular mechanisms by which the major human pathogen Vibrio cholerae defends against replication of the lysogenic phage, VP882. Activation of VP882 involves detection of the DPO quorum sensing molecule and our preliminary data indicate that V. cholerae employs the same molecule to mount a counteracting phage-defense response. Specifically, we show that DPO signaling results in the activation of a cryptic gene locus on the second chromosome of V. cholerae that gives rives to the production of a hydrophobic protein, called DacP (DPO-activated pseudogene). Mutation of dacP impairs recovery of V. cholerae from VP882 activation and when over-expressed DacP engages condensate formation that we hypothesize inhibits phage replication. We further provide evidence that defense against VP882 involves phenotypic heterogeneity of V. cholerae, involving three separate cell population displaying different responses to VP882 activation. Given that the interplay with phages plays a crucial role in the lifestyle and evolution of V. cholerae, we believe that the outlined research will reveal important information on how this major pathogen adapts to evade phage-mediated killing, but will also provide a more general view on how anti-phage systems encoded outside of canonical defense islands add to the anti-phage repertoire of the cell.
DFG Programme
Priority Programmes
