Pal, AK and Ghosh, A (2022) c-di-AMP signaling plays important role in determining antibiotic tolerance phenotypes of Mycobacterium smegmatis. In: Scientific Reports, 12 (1).
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Abstract
In this study, we probe the role of secondary messenger c-di-AMP in drug tolerance, which includes both persister and resistant mutant characterization of Mycobacterium smegmatis. Specifically, with the use of c-di-AMP null and overproducing mutants, we showed how c-di-AMP plays a significant role in resistance mutagenesis against antibiotics with different mechanisms of action. We elucidated the specific molecular mechanism linking the elevated intracellular c-di-AMP level and high mutant generation and highlighted the significance of non-homology-based DNA repair. Further investigation enabled us to identify the unique mutational landscape of target and non-target mutation categories linked to intracellular c-di-AMP levels. Overall fitness cost of unique target mutations was estimated in different strain backgrounds, and then we showed the critical role of c-di-AMP in driving epistatic interactions between resistance genes, resulting in the evolution of multi-drug tolerance. Finally, we identified the role of c-di-AMP in persister cells regrowth and mutant enrichment upon cessation of antibiotic treatment.
| Item Type: | Journal Article |
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| Publication: | Scientific Reports |
| Publisher: | Nature Research |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 22 Aug 2022 10:29 |
| Last Modified: | 22 Aug 2022 10:29 |
| URI: | https://eprints.iisc.ac.in/id/eprint/76142 |
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