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The H(2)O(2) inherently released by the mycobacterial minor subpopulation enhances the survival of the major kin subpopulation against rifampicin

Exposure to antibiotics most often generates oxidative stress in bacteria. Oxidative stress survival mechanisms would facilitate the evolution of antibiotic resistance. As part of an effort to understand oxidative stress survival mechanisms in mycobacteria, here we show that the minor subpopulation...

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Detalles Bibliográficos
Autores principales: Nair, Rashmi Ravindran, Sharan, Deepti, Srinivasan, Vijay, Mukkayyan, Nagaraja, Jakkala, Kishor, Ajitkumar, Parthasarathi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325904/
https://www.ncbi.nlm.nih.gov/pubmed/35909613
http://dx.doi.org/10.1016/j.crmicr.2022.100148
Descripción
Sumario:Exposure to antibiotics most often generates oxidative stress in bacteria. Oxidative stress survival mechanisms would facilitate the evolution of antibiotic resistance. As part of an effort to understand oxidative stress survival mechanisms in mycobacteria, here we show that the minor subpopulation (SCs; short-sized cells constituting 10% of the population) of Mycobacterium smegmatis significantly increased the survival of its major kin subpopulation (NCs; normal/long-sized cells constituting 90% of the population) in the mid-log-phase (MLP) cultures against the oxidative stress induced by rifampicin and exogenously added H(2)O(2) (positive control). We had earlier shown that the SCs in the MLP cultures inherently and naturally release significantly high levels of H(2)O(2) into the medium. Addition of the SCs’ culture supernatant, unlike the supernatant of the dimethylthiourea (H(2)O(2) scavenger) exposed SCs, enhanced the survival of NCs. It indicated that NCs’ survival required the H(2)O(2) present in the SCs’ supernatant. This H(2)O(2) transcriptionally induced high levels of catalase-peroxidase (KatG) in the NCs. The naturally high KatG levels in the NCs significantly neutralised the endogenous H(2)O(2) formed upon exposure to rifampicin or H(2)O(2), thereby enhancing the survival of NCs against oxidative stress. The absence of such enhanced survival in the furA-katG and katG knockout (KO) mutants of NCs in the presence of wild-type SCs, confirmed the requirement of the H(2)O(2) present in the SCs’ supernatant and NCs’ KatG for enhanced oxidative stress survival. The presence of SCs:NCs at 1:9 in the pulmonary tuberculosis patients’ sputum alludes to the clinical significance of the finding.