Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae Article Swipe
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· 2023
· Open Access
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· DOI: https://doi.org/10.1371/journal.ppat.1011250
· OA: W4327547435
As one of the most successful pathogenic organisms, Vibrio cholerae ( V . cholerae ) has evolved sophisticated regulatory mechanisms to overcome host stress. During long-term colonization by V . cholerae in adult mice, many spontaneous nonmotile mutants (approximately 10% at the fifth day post-infection) were identified. These mutations occurred primarily in conserved regions of the flagellar regulator genes flrA , flrC , and rpoN , as shown by Sanger and next-generation sequencing, and significantly increased fitness during colonization in adult mice. Intriguingly, instead of key genes in DNA repair systems ( mutS , nfo , xthA , uvrA ) or ROS and RNS scavenging systems ( katG , prxA , hmpA ), which were generally thought to be associated with bacterial mutagenesis, we found that deletion of the cyclin gene dps significantly increased the mutation rate (up to 53% at the fifth day post-infection) in V . cholerae . We further determined that the dps D65A and dps F46E point mutants showed a similar mutagenesis profile as the Δ dps mutant during long-term colonization in mice, which strongly indicated that the antioxidative function of Dps directly contributes to the development of V . cholerae nonmotile mutants. Methionine metabolism pathway may be one of the mechanism for Δ flrA , Δ flrC and Δ rpoN mutant increased colonization in adult mice. Our results revealed a new phenotype in which increased fitness of V . cholerae in the host gut via spontaneous production nonmotile mutants regulated by cyclin Dps, which may represent a novel adaptation strategy for directed evolution of pathogens in the host.
