Evolution of a cis-Acting SNP That Controls Type VI Secretion in Vibrio cholerae
ABSTRACT Mutations in regulatory mechanisms that control gene expression contribute to phenotypic diversity and thus facilitate the adaptation of microbes and other organisms to new niches. Comparative genomics can be used to infer rewiring of regulatory architecture based on large effect mutations...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00422-22 |
| _version_ | 1818545502703058944 |
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| author | Siu Lung Ng Sophia Kammann Gabi Steinbach Tobias Hoffmann Peter J. Yunker Brian K. Hammer |
| author_facet | Siu Lung Ng Sophia Kammann Gabi Steinbach Tobias Hoffmann Peter J. Yunker Brian K. Hammer |
| author_sort | Siu Lung Ng |
| collection | DOAJ |
| description | ABSTRACT Mutations in regulatory mechanisms that control gene expression contribute to phenotypic diversity and thus facilitate the adaptation of microbes and other organisms to new niches. Comparative genomics can be used to infer rewiring of regulatory architecture based on large effect mutations like loss or acquisition of transcription factors but may be insufficient to identify small changes in noncoding, intergenic DNA sequence of regulatory elements that drive phenotypic divergence. In human-derived Vibrio cholerae, the response to distinct chemical cues triggers production of multiple transcription factors that can regulate the type VI secretion system (T6), a broadly distributed weapon for interbacterial competition. However, to date, the signaling network remains poorly understood because no regulatory element has been identified for the major T6 locus. Here we identify a conserved cis-acting single nucleotide polymorphism (SNP) controlling T6 transcription and activity. Sequence alignment of the T6 regulatory region from diverse V. cholerae strains revealed conservation of the SNP that we rewired to interconvert V. cholerae T6 activity between chitin-inducible and constitutive states. This study supports a model of pathogen evolution through a noncoding cis-regulatory mutation and preexisting, active transcription factors that confers a different fitness advantage to tightly regulated strains inside a human host and unfettered strains adapted to environmental niches. IMPORTANCE Organisms sense external cues with regulatory circuits that trigger the production of transcription factors, which bind specific DNA sequences at promoters (“cis” regulatory elements) to activate target genes. Mutations of transcription factors or their regulatory elements create phenotypic diversity, allowing exploitation of new niches. Waterborne pathogen Vibrio cholerae encodes the type VI secretion system “nanoweapon” to kill competitor cells when activated. Despite identification of several transcription factors, no regulatory element has been identified in the promoter of the major type VI locus, to date. Combining phenotypic, genetic, and genomic analysis of diverse V. cholerae strains, we discovered a single nucleotide polymorphism in the type VI promoter that switches its killing activity between a constitutive state beneficial outside hosts and an inducible state for constraint in a host. Our results support a role for noncoding DNA in adaptation of this pathogen. |
| first_indexed | 2024-12-12T07:41:01Z |
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| id | doaj.art-0e2af0088b6543788db263e90aad7dee |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-12T07:41:01Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
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| spelling | doaj.art-0e2af0088b6543788db263e90aad7dee2022-12-22T00:32:47ZengAmerican Society for MicrobiologymBio2150-75112022-06-0113310.1128/mbio.00422-22Evolution of a cis-Acting SNP That Controls Type VI Secretion in Vibrio choleraeSiu Lung Ng0Sophia Kammann1Gabi Steinbach2Tobias Hoffmann3Peter J. Yunker4Brian K. Hammer5School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USASchool of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USASchool of Physics, Georgia Institute of Technology, Atlanta, Georgia, USASchool of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USASchool of Physics, Georgia Institute of Technology, Atlanta, Georgia, USASchool of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USAABSTRACT Mutations in regulatory mechanisms that control gene expression contribute to phenotypic diversity and thus facilitate the adaptation of microbes and other organisms to new niches. Comparative genomics can be used to infer rewiring of regulatory architecture based on large effect mutations like loss or acquisition of transcription factors but may be insufficient to identify small changes in noncoding, intergenic DNA sequence of regulatory elements that drive phenotypic divergence. In human-derived Vibrio cholerae, the response to distinct chemical cues triggers production of multiple transcription factors that can regulate the type VI secretion system (T6), a broadly distributed weapon for interbacterial competition. However, to date, the signaling network remains poorly understood because no regulatory element has been identified for the major T6 locus. Here we identify a conserved cis-acting single nucleotide polymorphism (SNP) controlling T6 transcription and activity. Sequence alignment of the T6 regulatory region from diverse V. cholerae strains revealed conservation of the SNP that we rewired to interconvert V. cholerae T6 activity between chitin-inducible and constitutive states. This study supports a model of pathogen evolution through a noncoding cis-regulatory mutation and preexisting, active transcription factors that confers a different fitness advantage to tightly regulated strains inside a human host and unfettered strains adapted to environmental niches. IMPORTANCE Organisms sense external cues with regulatory circuits that trigger the production of transcription factors, which bind specific DNA sequences at promoters (“cis” regulatory elements) to activate target genes. Mutations of transcription factors or their regulatory elements create phenotypic diversity, allowing exploitation of new niches. Waterborne pathogen Vibrio cholerae encodes the type VI secretion system “nanoweapon” to kill competitor cells when activated. Despite identification of several transcription factors, no regulatory element has been identified in the promoter of the major type VI locus, to date. Combining phenotypic, genetic, and genomic analysis of diverse V. cholerae strains, we discovered a single nucleotide polymorphism in the type VI promoter that switches its killing activity between a constitutive state beneficial outside hosts and an inducible state for constraint in a host. Our results support a role for noncoding DNA in adaptation of this pathogen.https://journals.asm.org/doi/10.1128/mbio.00422-22vibrio choleraeevolutiongene regulationsecretion systemssignal transductiontranscription factors |
| spellingShingle | Siu Lung Ng Sophia Kammann Gabi Steinbach Tobias Hoffmann Peter J. Yunker Brian K. Hammer Evolution of a cis-Acting SNP That Controls Type VI Secretion in Vibrio cholerae mBio vibrio cholerae evolution gene regulation secretion systems signal transduction transcription factors |
| title | Evolution of a cis-Acting SNP That Controls Type VI Secretion in Vibrio cholerae |
| title_full | Evolution of a cis-Acting SNP That Controls Type VI Secretion in Vibrio cholerae |
| title_fullStr | Evolution of a cis-Acting SNP That Controls Type VI Secretion in Vibrio cholerae |
| title_full_unstemmed | Evolution of a cis-Acting SNP That Controls Type VI Secretion in Vibrio cholerae |
| title_short | Evolution of a cis-Acting SNP That Controls Type VI Secretion in Vibrio cholerae |
| title_sort | evolution of a cis acting snp that controls type vi secretion in vibrio cholerae |
| topic | vibrio cholerae evolution gene regulation secretion systems signal transduction transcription factors |
| url | https://journals.asm.org/doi/10.1128/mbio.00422-22 |
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