Bacterial Gas Defenses

Nitric oxide (NO) and hydrogen sulfide (H2S) are well known signaling molecules in mammals. However, their functions in common bacteria are largely unknown. We demonstrated that various bacterial species generate NO and H2S enzymatically from arginine and cysteine, respectively, and that these two gases function to protect bacteria from oxidative stress and a wide range of antibiotics.

Moreover, bacterial NO and H2S act together to protect pathogens such as S. aureus and B. anthracis from immune attack. Microarray analyses indicated that endogenous NO and H2S regulate hundreds of bacterial genes. We are currently elucidating the molecular mechanisms of such regulation at the transcriptional and post-transcriptional levels.

We also study how these gases are regulated in bacteria and how they affect key physiological and clinically relevant processes such as biofilm formation, swarming, motility, sporulation, and quorum sensing.

Bacterial gasotransmitters.. In a subset of gram-positive bacteria, the aerobic production of NO is catalyzed by bNOS from the substrate L-argine through the stable intermediate, N-hydroxy-L-arginine to produce L-citrulline. Most bacteria are capable of endogenous H2S production via CSE/CBS and 3-MST pathways. CSE utilizes cystathionine or homocysteine as its substrates with different end products. CBS’s initial substrate is homocysteine but generates different end products from that of CSE. In a separate pathway 3MST metabolizes cysteine to produce pyruvate and H2S. NO can exert its effects in fundamental processes including those involved in oxidative stress response, host-pathogen interactions, biofilm formation, and antibiotic resistance through post-translational modification, transcriptional control, and chemical reactivity. H2S functions in a similar manner but the mechanistic details have yet to be worked out.