An interbacterial DNA deaminase toxin directly mutagenizes surviving target populations

Author:

de Moraes Marcos H1,Hsu FoSheng1,Huang Dean2ORCID,Bosch Dustin E3,Zeng Jun1,Radey Matthew C1,Simon Noah4,Ledvina Hannah E1,Frick Jacob P1,Wiggins Paul A2,Peterson S Brook1ORCID,Mougous Joseph D156ORCID

Affiliation:

1. Department of Microbiology, University of Washington School of Medicine, Seattle, United States

2. Department of Physics, University of Washington, Seattle, United States

3. Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, United States

4. Department of Biostatistics, University of Washington School of Public Health, Seattle, United States

5. Department of Biochemistry, University of Washington School of Medicine, Seattle, United States

6. Howard Hughes Medical Institute, University of Washington, Seattle, United States

Abstract

When bacterial cells come in contact, antagonism mediated by the delivery of toxins frequently ensues. The potential for such encounters to have long-term beneficial consequences in recipient cells has not been investigated. Here, we examined the effects of intoxication by DddA, a cytosine deaminase delivered via the type VI secretion system (T6SS) of Burkholderia cenocepacia. Despite its killing potential, we observed that several bacterial species resist DddA and instead accumulate mutations. These mutations can lead to the acquisition of antibiotic resistance, indicating that even in the absence of killing, interbacterial antagonism can have profound consequences on target populations. Investigation of additional toxins from the deaminase superfamily revealed that mutagenic activity is a common feature of these proteins, including a representative we show targets single-stranded DNA and displays a markedly divergent structure. Our findings suggest that a surprising consequence of antagonistic interactions between bacteria could be the promotion of adaptation via the action of directly mutagenic toxins.

Funder

National Institutes of Health

Howard Hughes Medical Institute

Cystic Fibrosis Foundation

Burroughs Wellcome Fund

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference85 articles.

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