The nitric oxide (NO) effector pathway governed by the NmlR regulog plays a critical role in bacterial defense against nitrosative stress. Nitric oxide, a reactive nitrogen species, can damage nucleic acids, proteins, and metal centers—especially iron-sulfur clusters—posing a serious threat to cellular viability. The NmlR regulog activates a suite of detoxification and repair genes in response to NO and other reactive species. NmlR is a transcriptional regulator that belongs to the MerR family and is activated under nitrosative or formaldehyde stress. Upon sensing NO or other electrophilic compounds, NmlR promotes the expression of protective genes involved in redox balancing, aldehyde detoxification, and thiol homeostasis. Key genes in the NmlR regulog include: nmlR – Encodes the NmlR transcriptional regulator, which senses NO or electrophilic stress and regulates its own expression as well as downstream detoxification genes. adhC – Encodes a glutathione-dependent alcohol dehydrogenase involved in the detoxification of S-nitrosoglutathione (GSNO), a major NO reservoir, converting it to less harmful compounds. adhY – Likely encodes a related alcohol dehydrogenase or NAD(P)H-dependent reductase involved in redox homeostasis. ypiA, yphK, yphJ, yphI, yphH – These genes encode a group of proteins that may participate in detoxification, stress response, or metabolic reprogramming under nitrosative stress. While their specific functions are not fully characterized, they are consistently co-regulated by NmlR and are upregulated during NO exposure or oxidative conditions, suggesting auxiliary roles in cellular protection.

Nitric oxide - NmlR References