Mycobacteria Tolerate Carbon Monoxide by Remodeling Their Respiratory Chain.

Carbon monoxide (CO) gas is infamous for its acute toxicity. This toxicity predominantly stems from its tendency to form carbonyl complexes with transition metals, thus inhibiting the heme-prosthetic groups of proteins, including respiratory terminal oxidases. While CO has been proposed as an antibacterial agent, the evidence supporting its toxicity toward 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 is highly resistant to the toxic effects of CO, exhibiting only minor inhibition of growth when cultured in its presence. We profiled the proteome of during growth in CO, identifying strong induction of cytochrome oxidase and members of the regulon, but relatively few other changes. We show that the activity of cytochrome oxidase is resistant to CO, whereas cytochrome oxidase is strongly inhibited by this gas. Consistent with these findings, growth analysis shows that lacking cytochrome oxidase displays a significant growth defect in the presence of CO, while induction of the regulon appears to be unimportant for adaptation to CO. Altogether, our findings indicate that has considerable resistance to CO and benefits from respiratory flexibility to withstand its inhibitory effects. Carbon monoxide has an infamous reputation as a toxic gas, and it has been suggested that it has potential as an antibacterial agent. Despite this, how bacteria resist its toxic effects is not well understood. In this study, we investigated how CO influences growth, proteome, and aerobic respiration of wild-type and mutant strains of We show that this bacterium produces the CO-resistant cytochrome oxidase to tolerate poisoning of its CO-sensitive complex IV homolog. Further, we show that aside from this remodeling of its respiratory chain, makes few other functional changes to its proteome, suggesting it has a high level of inherent resistance to CO.