Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.10.245365v1?rss=1 Authors: Anand, K., Tripathi, A., Shukla, K., Malhotra, N., Jamithireddy, A., Jha, R. K., Chaudhury, S. N., Rajmani, R. S., Ramesh, A., Nagaraja, V., Gopal, B., Nagaraju, G., Seshayee, A. S. N., Singh, A. Abstract: Host-inducible nitric oxide (NO) suppresses Mycobacterium tuberculosis(Mtb) without eradicating it. Mechanisms underlying the persistence of residual bacteria in a hostile host environment are not known. Since NO damages Fe-S clusters of essential enzymes, the mechanism used to repair Fe-S clusters could help Mtb persist in host tissues. Here, we show that Mtb utilizes the suf operon (Rv1460-Rv1466) for Fe-S cluster biogenesis to persist under NO stress. Further, transcriptional repressor SufR (Rv1460) senses NO through its 4Fe-4S cluster to directly regulate Suf-meditated Fe-S cluster biogenesis. We discovered that NO inflicted irreversible damage upon Fe-S clusters to exhaust respiratory reserves and redox buffering capacity of Mtb{Delta}sufR. Importantly, Mtb{Delta}sufR failed to recover from a NO-induced non-growing state and displayed persistence defect inside immune-activated macrophages and murine lungs in a NO-dependent manner. Data suggest that SufR is a sensor of NO that supports persistence by reprogramming Fe-S cluster metabolism and bioenergetics of Mtb. Copy rights belong to original authors. Visit the link for more info