Proteome Profiling of Mycobacterium tuberculosis Cells Exposed to Nitrosative Stress

Alemayehu Godana Birhanu; Marta Gómez-Muñoz; Shewit Kalayou; Tahira Riaz; Timo Lutter; Solomon Abebe Yimer; Markos Abebe; Tone Tønjum

doi:10.1021/acsomega.1c05923

Proteome Profiling of Mycobacterium tuberculosis Cells Exposed to Nitrosative Stress

ACS Omega. 2022 Jan 14;7(4):3470-3482. doi: 10.1021/acsomega.1c05923. eCollection 2022 Feb 1.

Authors

Alemayehu Godana Birhanu^{1

2}, Marta Gómez-Muñoz¹, Shewit Kalayou^{3

4}, Tahira Riaz¹, Timo Lutter¹, Solomon Abebe Yimer^{1

5}, Markos Abebe⁶, Tone Tønjum^{1

3}

Affiliations

¹ Department of Microbiology, University of Oslo, P.O. Box 4950, Nydalen, NO-0424 Oslo, Norway.
² Institute of Biotechnology, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia.
³ Department of Microbiology, Oslo University Hospital, P.O. Box 4950, Nydalen, NO-0424 Oslo, Norway.
⁴ International Center of Insect Physiology and Ecology (ICIPE), P.O. Box 30772-00100 Nairobi, Kenya.
⁵ Coalition for Epidemic Preparedness Innovations (CEPI), P.O. Box 123, Torshov, 0412 Oslo, Norway.
⁶ Armauer Hansen Research Institute, Jimma Road, P.O. Box 1005 Addis Ababa, Ethiopia.

Abstract

Reactive nitrogen species (RNS) are secreted by human cells in response to infection by Mycobacterium tuberculosis (Mtb). Although RNS can kill Mtb under some circumstances, Mtb can adapt and survive in the presence of RNS by a process that involves modulation of gene expression. Previous studies focused primarily on stress-related changes in the Mtb transcriptome. This study unveils changes in the Mtb proteome in response to a sub-lethal dose of nitric oxide (NO) over several hours of exposure. Proteins were identified using liquid chromatography coupled with electrospray ionization mass spectrometry (LC-MS/MS). A total of 2911 Mtb proteins were identified, of which 581 were differentially abundant (DA) after exposure to NO in at least one of the four time points (30 min, 2 h, 6 h, and 20 h). The proteomic response to NO was marked by two phases, with few DA proteins in the early phase and a multitude of DA proteins in the later phase. The efflux pump Rv1687 stood out as being the only protein more abundant at all the time points and might play a role in the early protection of Mtb against nitrosative stress. These changes appeared to be compensatory in nature, contributing to iron homeostasis, energy metabolism, and other stress responses. This study thereby provides new insights into the response of Mtb to NO at the level of proteomics.