You win some, you lose some. Loss of CitAB/DpiAB as a novel instance of pathoadaptive evolution in Shigella flexneri

Candidate: Zaid Shahid 
Supervisor: Dr. Joseph McPhee

Abstract:

Previous work in our lab has found that multiple Shigella species exhibit conserved loss of multiple two-component signaling systems (TCS) that are typically conserved in E. coli strains. One such signaling system is the citAB/dpiAB system. In E. coli, the citAB/dpiAB genes control citrate utilization under anaerobic conditions. In addition to this metabolic role, dpiAB/citAB also interferes with plasmid inheritance and gene expression of AT-rich plasmids in E. coli. Our findings indicate that citAB/dpiAB interferes with glycolysis and the Entner- Doudoroff pathway, leading to a pronounced fitness defect under microaerophilic conditions and reduced competitive ability against wild-type strains. Additionally, we found there is a citAB/dpiAB mediated attenuation of the virulence capacity in S. flexneri along correlating with increased loss of the virulence plasmid. Our work will add to a growing body of evidence that highlights gene loss as a pathoadaptive strategy and underscores how antivirulence genes are a significant evolutionary pressure driving genetic heterogeneity among Enterobacterales species.