Dataset Information

Proteomic and epi/proteomic response of Mycobacterium tuberculosis to nitric oxide stress

ABSTRACT: Reactive nitrogen species (RNS) are the major antimicrobial molecules secreted by host cells to tackle Mycobacterium tuberculosis (Mtb) infection. Mtb respond and adapt to adverse environmental stressors by changes in gene expression, ensuring their survival. This adaptation process is mediated by a combination of transcriptional regulatory networks that result in altered gene expression and enzyme (protein) activities. Previous studies emphasized primarily on transcriptomic response of Mtb to different environmental stresses, including RNS. In this study, the proteomic response of Mtb to sublethal doses of RNS stress after 30 minutes, 2 hours, 6 hours and 20 hours was explored. We used liquid chromatography coupled with electrospray ionization mass spectrometry (LC-MS/MS) to elucidate the proteomic response of Mtb to RNS. Quantitative proteomic analysis revealed identification of 2911 proteins and 6460 acylations in Mtb. A total of 581 unique proteins were found to be affected by RNS at different time points. Multiple-sample test revealed 297 differentially regulated proteins across the four time points. Furthermore, multiple-sample test identified 127 differentially acylated sites on 94 proteins. Marked changes in proteomic response was observed at later time points, most of which were compensatory responses involved in SOS response, iron homeostasis, energy metabolism and other stress responses. This study provides an improved understanding of the dynamic proteomic response of Mtb to RNS and identification of key molecular switches, which is the basis of controlling bacterial growth in different environmental setting.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mycobacterium Tuberculosis H37rv

SUBMITTER: Alemayehu Godana Birhanu

LAB HEAD: Alemayehu Godana Birhanu

PROVIDER: PXD016006 | Pride | 2022-02-15

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	AcylationKSTYSites.txt	Txt
	H37Rv_Cntr_20h_R1__5128.raw	Raw
	H37Rv_Cntr_20h_R2__5139.raw	Raw
	H37Rv_Cntr_20h_R3__5169.raw	Raw
	H37Rv_Cntr_2h_R1__5124.raw	Raw

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Publications

Proteome Profiling of <i>Mycobacterium tuberculosis</i> Cells Exposed to Nitrosative Stress.

Birhanu Alemayehu Godana AG Gómez-Muñoz Marta M Kalayou Shewit S Riaz Tahira T Lutter Timo T Yimer Solomon Abebe SA Abebe Markos M Tønjum Tone T

ACS omega 20220114 4

Reactive nitrogen species (RNS) are secreted by human cells in response to infection by <i>Mycobacterium tuberculosis</i> (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 ex ...[more]

PMID: 35128256

Similar Datasets

Project description:Reactive nitrogen species (RNS) derived from dietary and salivary inorganic nitrates (NO3-) foment innate host defenses associated with the acidity of the stomach. The mechanisms by which these reactive species exert antibiotic activity in the gastric lumen are, however, poorly understood. To identify targets of RNS, the genetically tractable acid tolerance response (ATR) that enables enteropathogens to survive the harsh acidity of the stomach was screened for signaling pathways responsive to RNS. The nitric oxide (NO) donor spermine NONOate derepressed the Fur regulon that controls secondary lines of resistance against organic acids. Despite inducing a Fur-mediated adaptive response, acidified RNS largely boosted gastric host defenses as demonstrated by the fact that Salmonella bacteria exposed to spermine NONOate during mildly acidic conditions were not only shed in low amounts in feces, but also exhibited ameliorated oral virulence. NO prevented Salmonella from mounting a de novo ATR, but was unable to suppress an already functional protective response, indicating that RNS target regulatory cascades but not the effectors that defend against the rigors of gastric acidity. Transcriptional and translational analyses revealed that the PhoPQ signaling cascade is a critical ATR target of NO in rapidly growing Salmonella. Inhibition of PhoPQ signaling appears to contribute to most of the NO-mediated abrogation of the ATR in log phase bacteria, because the augmented acid sensitivity of phoQ-deficient Salmonella was not further enhanced after RNS treatment. Since PhoPQ-regulated acid resistance is widespread in enteric pathogens, the RNS-mediated inhibition of the Salmonella ATR described herein may represent a common component of the innate host defenses of the gastric lumen. Keywords: acid tolerance response, nitric oxide Microarray analyses were conducted comparing transcript levels of log-phase Salmonella cultured in minimal E salts + 0.4% glucose, pH 4.4 in the presence or absence of 250 ÂµM spermine NONOate for 1 hour. Microarrays were performed in triplicate under identical conditions (3 biological replicates).