Proteomic analysis reveals that sulfamethoxazole induces oxidative stress in M. tuberculosis
| Autor: | R.-D. Pietersen, P. D. van Helden, L. Macingwana, C. Mdladla, David L. Tabb, R. Sarkar, Andile H. Ngwane, Bienyameen Baker, Ian Wiid |
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| Rok vydání: | 2018 |
| Předmět: |
Proteomics
0301 basic medicine Microbiology (medical) Tuberculosis Sulfamethoxazole 030106 microbiology Immunology Antitubercular Agents urologic and male genital diseases medicine.disease_cause Microbiology Mycobacterium tuberculosis 03 medical and health sciences Bacterial Proteins Tandem Mass Spectrometry medicine Ethambutol Chromatography Reverse-Phase biology Chemistry Isoniazid Gene Expression Regulation Bacterial Pyrazinamide bacterial infections and mycoses biology.organism_classification medicine.disease female genital diseases and pregnancy complications Oxidative Stress 030104 developmental biology Infectious Diseases Oxidative stress Rifampicin medicine.drug |
| Zdroj: | Tuberculosis. 111:78-85 |
| ISSN: | 1472-9792 |
| Popis: | The emerging resistance of tuberculosis (TB) to current first line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) warrants alternative treatment approaches with broad-spectrum efficacy. Previously, we have shown that sulfamethoxazole (SMX) has synergestic activity with rifampicin against Mycobacterium tuberculosis. The primary target of SMX is folP1 in mycobacteria; however, SMX may affect other secondary targets in M. tuberculosis. This study investigated the potential additional targets of SMX in a clinical isolate of M. tuberculosis using Orbitrap mass spectrometry to identify differentially expressed proteins following treatment with a sub-lethal concentration of SMX. Raw data have been deposited as ProteomeXchange accession PXD009315. Our proteomic analysis identified approximately 1500 proteins in total of which 45 proteins were differentially regulated as a result of SMX treatment. These included 25 upregulated and 20 downregulated proteins. The oxidative stress proteins (Rv2428, AhpC and Rv2394, GgtB) and an enzyme from the electron transport chain (Ndh-II, Rv1854c) were found to be upregulated. Gene expression analysis correlated with the observed proteomic changes. In conclusion our results show that SMX treatment of a drug sensitive M. tuberculosis clinical isolate resulted in the regulation of proteins involved in the oxidative stress response, indicating the induction of oxidative stress by SMX in mycobacteria. |
| Databáze: | OpenAIRE |
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