AUTHOR=Kim Na-Kyeong , Baek Jong-Eun , Lee Ye-Jin , Oh Yuna , Oh Jeong-Il 

TITLE=Rel-dependent decrease in the expression of ribosomal protein genes by inhibition of the respiratory electron transport chain in Mycobacterium smegmatis

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1448277

DOI=10.3389/fmicb.2024.1448277

ISSN=1664-302X

ABSTRACT=<p>In this study, we demonstrated that both the expression of most ribosomal protein genes and the amount of ribosomes were decreased in the Δ<italic>aa</italic><sub>3</sub> mutant of <italic>Mycobacterium smegmatis</italic>, in which the major terminal oxidase (<italic>aa</italic><sub>3</sub> cytochrome <italic>c</italic> oxidase) of the respiratory electron transport chain (ETC) is inactivated, compared to those in the wild-type strain. Deletion of the <italic>rel</italic> gene encoding the major (p)ppGpp synthetase in the background of the Δ<italic>aa</italic><sub>3</sub> mutant restored the reduced expression of ribosomal protein genes, suggesting that inhibition of the respiratory ETC leads to the Rel-dependent stringent response (SR) in this bacterium. Both a decrease in the expression of ribosomal protein genes by overexpression of <italic>rel</italic> and the increased expression of <italic>rel</italic> in the Δ<italic>aa</italic><sub>3</sub> mutant relative to the wild-type strain support the Rel-dependent induction of SR in the Δ<italic>aa</italic><sub>3</sub> mutant. We also demonstrated that the expression of ribosomal protein genes was decreased in <italic>M. smegmatis</italic> exposed to respiration-inhibitory conditions, such as KCN and bedaquiline treatment, null mutation of the cytochrome <italic>bcc</italic><sub>1</sub> complex, and hypoxia. The MprBA-SigE-SigB regulatory pathway was implicated in both the increased expression of <italic>rel</italic> and the decreased expression of ribosomal protein genes in the Δ<italic>aa</italic><sub>3</sub> mutant of <italic>M. smegmatis</italic>.</p>