Fusobacterium nucleatum: strategies for adapting to aerobic stress

Fusobacterium nucleatum-a gram-negative anaerobe-is commensal to the oral cavity, where it plays an important role in the maturation of the oral biofilm. The bacterium is also an opportunistic pathogen, given its association with systemic infections and cancer progression. Although residing in largely anoxic microenvironments within the oral biofilm, F. nucleatum encounters oxygen (O₂) present in the circulating saliva and reactive oxygen species formed endogenously, by an activated immune system or neighboring oral commensal streptococci. This review explores the bacterium's adaptive mechanisms that enable survival under oxidative stress. We discuss how F. nucleatum mitigates oxidative damage and aerobic stress through common detoxifying and repair enzymes such as peroxiredoxins, methionine sulfoxide reductases, and rubrerythrin and through the activity of the recently identified multicomponent enzyme, termed butyryl-CoA oxygen oxidoreductase. Turnover by the latter enzyme enables F. nucleatum to exploit molecular oxygen for the conservation of energy. Additionally, we discuss how a two-component signal transduction system, ModRS, a global regulator of oxidative stress, functions in part to reprogram core metabolism to counterbalance the inactivation of a glycyl radical enzyme hypersensitive to O₂. Our findings provide new insight into how F. nucleatum resists fluctuating dioxygen environments, shedding light on its persistence in extraoral sites and its potential role in disease progression.