The Capacity of To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas.

This study was conducted to investigate the role of iron deprivation in the persistence of We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies. One-third of the world population may harbor persistent , causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain persistence in infected individuals. Iron is an essential nutrient for growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which likely experiences drastic Fe deprivation and, second, that Fe-starved is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent , which can be exploited for the design of new antitubercular therapies.