Experimental Evolution Reveals Redox State Modulates Mycobacterial Pathogenicity.

Understanding how has evolved into a professional pathogen is helpful in studying its pathogenesis and for designing vaccines. We investigated how the evolutionary adaptation of mc51 to an important clinical stressor HO allows bacteria to undergo coordinated genetic mutations, resulting in increased pathogenicity. Whole-genome sequencing identified a mutation site in the gene, which caused increased expression of . Using a Wayne dormancy model, mc51 showed a growth advantage over its parental strain mc155 in recovering from dormancy under anaerobic conditions. Meanwhile, the high level of KatG in mc51 was accompanied by a low level of ATP, which meant that mc51 is at a low respiratory level. Additionally, the redox-related protein Rv1996 showed different phenotypes in different specific redox states in mc155 and mc51, BCG, and mc7000. In conclusion, our study shows that the same gene presents different phenotypes under different physiological conditions. This may partly explain why and have similar virulence factors and signaling transduction systems such as two-component systems and sigma factors, but due to the different redox states in the corresponding bacteria, is a nonpathogen, while is a pathogen. As mc51 overcomes its shortcomings of rapid removal, it can potentially be developed as a vaccine vector.