Apr 9, 2020

Mycobacteria tolerate carbon monoxide by remodelling their respiratory chain

BioRxiv : the Preprint Server for Biology
K. BaylyChris Greening


Carbon monoxide (CO) is a gas infamous for its acute toxicity. The toxicity of CO predominantly stems from its tendency to form carbonyl complexes with transition metals, thus inhibiting the heme-prosthetic groups of proteins, including the terminal oxidases of the respiratory chain. While CO has been proposed as an antibacterial agent, the evidence supporting its toxicity towards bacteria is equivocal, and its cellular targets remain poorly defined. In this work, we investigate the physiological response of mycobacteria to CO. We show that Mycobacterium smegmatis is highly resistant to the toxic effects of CO, exhibiting normal growth parameters when cultured in its presence. We profiled the proteome of M. smegmatis during growth in CO, identifying strong induction of cytochrome bd oxidase and members of the dos regulon, but relatively few other changes. We show that the activity of cytochrome bd oxidase is resistant to CO, whereas cytochrome bcc-aa3 oxidase is strongly inhibited by this gas. Consistent with these findings, growth analysis shows that M. smegmatis lacking cytochrome bd oxidase displays a significant growth defect in the presence of CO, while induction of the dos regulon appears to be unimportant for adaption to...Continue Reading

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Research Subject
Hydrogenobyrinic Acid a, C-diamide Synthase (Glutamine-hydrolysing) Activity
Cobyrinic Acid a, C-diamide Synthase Activity

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