Proteome Profiling of Mycobacterium tuberculosis Cells Exposed to Nitrosative Stress

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.