Towards Understanding the Molecular Basis of Nitric Oxide-Regulated Group Behaviors in Pathogenic Bacteria

Pathogenic bacteria have many strategies for causing disease in humans. One such strategy is the ability to live both as single-celled motile organisms or as part of a community of bacteria called a biofilm. Biofilms are frequently adhered to biotic or abiotic surfaces and are extremely antibiotic resistant. Upon biofilm dispersal, bacteria become more antibiotic susceptible but are also able to readily infect another host. Various studies have shown that low, nontoxic levels of nitric oxide (NO) may induce biofilm dispersal in many bacterial species. While the molecular details of this phenotype remain largely unknown, in several species, NO has been implicated in biofilm-to-planktonic cell transitions via ligation to 1 of 2 characterized NO sensors, NosP or H-NOX. Based on the data available to date, it appears that NO binding to H-NOX or NosP triggers a downstream response based on changes in cellular cyclic di-GMP concentrations and/or the modulation of quorum sensing. In order to develop applications for control of biofilm infections, the identification and characterization of biofilm dispersal mechanisms is vital. This review focuses on the efforts made to understand NO-mediated control of H-NOX and NosP pathways in the 3 pathogenic bacteria Legionella pneumophila, Vibrio cholerae, and Pseudomonas aeruginosa.