Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae.
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011250 |
| _version_ | 1827943695357313024 |
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| author | Mei Luo Guozhong Chen Chunrong Yi Baoshuai Xue Xiaoman Yang Yao Ma Zixin Qin Jin Yan Xiaoyun Liu Zhi Liu |
| author_facet | Mei Luo Guozhong Chen Chunrong Yi Baoshuai Xue Xiaoman Yang Yao Ma Zixin Qin Jin Yan Xiaoyun Liu Zhi Liu |
| author_sort | Mei Luo |
| collection | DOAJ |
| description | 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 dpsD65A and dpsF46E point mutants showed a similar mutagenesis profile as the Δdps 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 ΔflrA, ΔflrC and ΔrpoN 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. |
| first_indexed | 2024-03-13T10:19:15Z |
| format | Article |
| id | doaj.art-d814982191c14e3e8884ab11b34310de |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-13T10:19:15Z |
| publishDate | 2023-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-d814982191c14e3e8884ab11b34310de2023-05-21T05:31:09ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-03-01193e101125010.1371/journal.ppat.1011250Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae.Mei LuoGuozhong ChenChunrong YiBaoshuai XueXiaoman YangYao MaZixin QinJin YanXiaoyun LiuZhi LiuAs 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 dpsD65A and dpsF46E point mutants showed a similar mutagenesis profile as the Δdps 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 ΔflrA, ΔflrC and ΔrpoN 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.https://doi.org/10.1371/journal.ppat.1011250 |
| spellingShingle | Mei Luo Guozhong Chen Chunrong Yi Baoshuai Xue Xiaoman Yang Yao Ma Zixin Qin Jin Yan Xiaoyun Liu Zhi Liu Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae. PLoS Pathogens |
| title | Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae. |
| title_full | Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae. |
| title_fullStr | Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae. |
| title_full_unstemmed | Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae. |
| title_short | Dps-dependent in vivo mutation enhances long-term host adaptation in Vibrio cholerae. |
| title_sort | dps dependent in vivo mutation enhances long term host adaptation in vibrio cholerae |
| url | https://doi.org/10.1371/journal.ppat.1011250 |
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