Delayed effects of transcriptional responses in Mycobacterium tuberculosis exposed to nitric oxide suggest other mechanisms involved in survival.

Teresa Cortes; Olga T Schubert ORCID logo; Amir Banaei-Esfahani ORCID logo; Ben C Collins ORCID logo; Ruedi Aebersold ORCID logo; Douglas B Young; (2017) Delayed effects of transcriptional responses in Mycobacterium tuberculosis exposed to nitric oxide suggest other mechanisms involved in survival. Scientific reports, 7 (1). 8208-. ISSN 2045-2322 DOI: 10.1038/s41598-017-08306-1
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Mycobacterium tuberculosis has succeeded as a human pathogen for tens of thousands of years thanks to its ability to resist and adapt to the adverse conditions it encounters upon infection. Bacterial adaptation to stress is commonly viewed in the context of transcriptional regulation, with the implicit expectation that an initial transcriptomic response is tightly coupled to an ensuing proteomic response. However, after challenging M. tuberculosis with nitric oxide we found that the rapid transcriptional responses, detectable within minutes of nitric oxide exposure, typically took several hours to manifest on the protein level. Furthermore, early proteomic responses were dominated by the degradation of a set of proteins, specifically those containing damaged iron-sulphur clusters. Overall, our findings are consistent with transcriptional responses participating mostly in late-stage recovery rather than in generating an immediate resistance to nitric oxide stress, suggesting that survival of M. tuberculosis under acute stress is contingent on mechanisms other than transcriptional regulation. These findings provide a revised molecular understanding of an important human pathogen.


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