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

Abstract

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.

Solution structures of the Shewanella woodyiH‐NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP‐051

“…Heme‐nitric oxide/oxygen binding (H‐NOX) domains are gas‐sensing hemoproteins that bind dissolved gases and induce signaling responses in a wide variety of organisms. In prokaryotes, H‐NOX sensors function as both stand‐alone proteins and as members of multidomain proteins, and respond to nitric oxide (NO), oxygen and potentially other ligands such as carbon monoxide (CO) to induce a signaling cascade 1,2 . Obligate anaerobes use H‐NOX domains to escape dioxygen as part of a methyl‐accepting chemotaxis system while a variety of bacteria use stand‐alone H‐NOX proteins to sense NO and repress biofilm formation through lowering cyclic di‐GMP levels.…”

“…In prokaryotes, H-NOX sensors function as both stand-alone proteins and as members of multidomain proteins, and respond to nitric oxide (NO), oxygen and potentially other ligands such as carbon monoxide (CO) to induce a signaling cascade. 1,2 Obligate anaerobes use H-NOX domains to escape dioxygen as part of a methyl-accepting chemotaxis system while a variety of bacteria use stand-alone H-NOX proteins to sense NO and repress biofilm formation through lowering cyclic di-GMP levels. In the latter case, H-NOX proteins may participate in a two-component signaling cascade, inhibiting a histidine kinase that stimulates a cyclic di-GMP synthase, or by directly stimulating the phosphodiesterase activity, and inhibiting the cyclase activity, of a cyclic di-GMP synthase/phosphodiesterase fusion protein.…”

Deleterious Effects of an Air Pollutant (NO2) on a Selection of Commensal Skin Bacterial Strains, Potential Contributor to Dysbiosis?

“…Reactive nitrogen species, i.e., molecules generated mainly from NO, are often considered as atmospheric pollutants such as NO 2 , its main representative in ambient air. However, NO is synthetized in vivo by cells and involved at various biological functions such as innate immunity ( Bogdan, 2015 ) or cell signaling ( Martínez-Ruiz et al, 2011 ) including in bacteria ( Williams and Boon, 2019 ). NO and RNS exert in macrophages antimicrobial effects allowing host protection against pathogens ( Bogdan, 2015 ).…”

NO donors and NO delivery methods for controlling biofilms in chronic lung infections

“…High concentrations of intracellular c-di-GMP promote the switch from planktonic growth modes to biofilm formation (Römling et al 2013 ). NO decreases intracellular c-di-GMP levels in P. aeruginosa via directly or indirectly stimulating several PDEs, such as NbdA, DipA and RbdA (Barraud et al 2009a ; Morgan et al 2006 ; Petrova and Sauer 2012a ; Petrova and Sauer 2012b ; Li et al 2013 ) (See reviews by Cutruzzolà and Frankenberg-Dinkel 2016 ; Williams and Boon 2019 for detailed molecular mechanisms). Low-dose NO was also proven to prevent or disperse biofilms formed by many different species, although different concentrations and donors were required (Arora et al 2015 ; Thompson et al 2019 ; Islam et al 2020 ).…”