The cytochrome d oxidase complex regulated by fexA is an Achilles' heel in the survival of .

is a halophilic estuarine bacterium causing severe opportunistic infections. To successfully establish an infection, must adapt to redox fluctuations in vivo. In the present study, we show that deletion of fexA gene caused hypersensitivity to acid and reactive oxygen species. The mutant exhibited severe in vivo survival defects. For deeper understanding the role of gene on the successful infection, we analyzed differentially expressed genes in mutant in comparison with wild type under aerobic, anaerobic or in vivo culture conditions by genome-scale DNA microarray analyses. Twenty-two genes were downregulated in the mutant under all three culture conditions. Among them, appeared to dominantly contribute to the defective phenotypes of the mutant. The deletion induced compensatory point mutations in the promoter region over subcultures, suggesting essentiality. Those point mutations (PSMs) restored bacterial growth, motility, cytotoxicity ATP production and mouse lethality in the mutant. These results indicate that the operon, being regulated by , plays a crucial role in survival under redox-fluctuating in vivo conditions. The FexA-CydAB axis should serve an Achilles heel in the development of therapeutic regimens against infection.