Gap-Gaupool, B., Glenn, S.M., Milburn, E. et al. (13 more authors) (2024) Nitric oxide induces the distinct invisibility phenotype of Mycobacterium tuberculosis. Communications Biology, 7. 1206.
Abstract
During infection Mycobacterium tuberculosis (Mtb) forms physiologically distinct subpopulations that are recalcitrant to treatment and undetectable using standard diagnostics. These difficult to culture or differentially culturable (DC) Mtb are revealed in liquid media, their revival is often stimulated by resuscitation-promoting factors (Rpf) and prevented by Rpf inhibitors. Here, we investigated the role of nitric oxide (NO) in promoting the DC phenotype. Rpf-dependent DC Mtb were detected following infection of interferon-γ-induced macrophages capable of producing NO, but not when inducible NO synthase was inactivated. After exposure of Mtb to a new donor for sustained NO release (named NOD), the majority of viable cells were Rpf-dependent and undetectable on solid media. Gene expression analyses revealed a broad transcriptional response to NOD, including down-regulation of all five rpf genes. The DC phenotype was partially reverted by over-expression of Rpfs which promoted peptidoglycan remodelling. Thus, NO plays a central role in the generation of Rpf-dependent Mtb, with implications for improving tuberculosis diagnostics and treatments.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | Bacteriology; Pathogens |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Sep 2024 11:35 |
Last Modified: | 30 Sep 2024 11:35 |
Published Version: | http://dx.doi.org/10.1038/s42003-024-06912-0 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1038/s42003-024-06912-0 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:217763 |