Deciphering nitric oxide stress in bacteria with quantitative modeling

Many pathogens depend on nitric oxide (NO) detoxification and repair to establish an infection, and inhibitors of these systems are under investigation as next-generation antibiotics. Because of the broad reactivity of NO and its derivatives with biomolecules, a deep understanding of how pathogens sense and respond to NO, as an integrated system, has been elusive. Quantitative kinetic modeling has been proposed as a method to enhance analysis and understanding of NO stress at the systems-level. Here we review the motivation for, current state of, and future prospects of quantitative modeling of NO stress in bacteria, and suggest that such mathematical approaches would prove equally useful in the study of other broadly reactive antimicrobials, such as hydrogen peroxide (H2O2).