The role of cytochrome oxidases in bacterial virulence

Bacterial physiology plays an important role in virulence. Being a pathogen is energetically expensive, requiring the production of specialized virulence factors and other proteins that enable survival within the host. The most efficient way for bacteria to generate the energy required for virulence is by electron-coupled oxidative phosphorylation, with oxygen as the terminal acceptor, also called aerobic respiration. Cytochrome oxidases are critical components of the electron transport chain used in aerobic respiration. Studies on the role of cytochrome oxidases during infection in clinically relevant bacteria have shown that they are often critical, even in low-oxygen environments, such as the gastrointestinal tract. Cytochrome oxidases-especially bd-type, the class most associated with virulence-are thus being explored as possible antimicrobial drug targets. However, the mechanisms underlying the role of cytochrome oxidases, especially non-bd-type cytochrome oxidases, during infection remain poorly understood in most organisms. In this review, we examine what is known about the role of cytochrome oxidases during infection, highlighting four pathogens: Mycobacterium tuberculosis and uropathogenic Escherichia coli, in which the role of bd-type cytochrome oxidases during infection has been investigated mechanistically, and Vibrio cholerae and Bordetella bronchiseptica, in which non-bd-type cytochrome oxidases contribute to infection. These examples indicate the need to assess what role cytochrome oxidases play in a wider array of bacterial pathogens.