Nitric oxide antimicrobial effects

Green, S.J. and Nacy, C.A., Antimicrobial and immunopathologic effect of cytokine-induced nitric oxide synthesis, Curr. Opin. Infect. Dis., 6, 384, 1993. 

Small molecules, such as nitric oxide and salicylic acid, have exhibited strong antimicrobial effects and have shown the ability to readily disperse biofilms. An important advantage of these small molecnles is that bacteria often do not develop resistance to them. In addition, they are often more biocompatible and also resistant to thrombosis, for example, nitric oxide. It seems that small molecnle treatment of bacterial infections with controlled delivery of snitable doses of small molecule (e.g., nitric oxide) is a very desirable goal. Development of nitric oxide- or other small molecule-re-leasing polyurethanes will provide promising approaches to antibiotic therapies with improved biocompatibility. 

Mcmullin, B.B., Chittock, D.R., Roscoe, D.L., Garcha, H., Wang, L., Miller, C.C., 2005. The antimicrobial effect of nitric oxide on the bacteria that cause nosocomial pneumonia in mechanically ventilated patients in the intensive care unit Respiratory Care 50,1451-1456. 

Regev-Shoshani, G., Ko, M., Miller, C., Av-Gay, Y., 2010. Slow release of nitric oxide from charged catheters and its effect on biofilm formation by Escherichia coli. Antimicrobial Agents and Chemotherapy 54, 273-279. 

Other possible modes of action may centre on stimulation of T cells (this occurred with the live aroA mutant of A. salmonicida Marsden et al., 1996), which introduces the role of cellular and innate rather than humoral immunity as the mode of action. For this, examples include A. hydrophila LPS (Baba et al., 1988) and E. tarda ECPs (Lee et al., 2010). Of course, there could be involvement of humoral, cell-mediated and innate immune parameters as stated for the i.p. administration of a live auxotrophic aroA mutant of A. hydrophila with effectiveness against furunculosis in rainbow trout (Vivas et al, 2004). Other possibilities include the evidence that one commercial formalized whole cell V. anguillarum vaccine induces Mx gene (these are inducible by Type I interferons and have a role in antiviral activity) expression in Atlantic salmon after administration intraperitoneally (Acosta et al., 2004). In another example, vaccination with P. damselae subsp. piscicida cells were found to enhance the nitric oxide response, i.e. the production of reactive nitrogen intermediates with their antimicrobial activities, to infection with the pathogen, and is correlated with the level of protection (Acosta et al., 2005). There was inhibition of F columnare adhesion to the skin of immersion vaccinated eel (Mano et al., 1996). Finally, mention will be made of a possible mechanism of protection of V. anguillarum vaccines that may well involve the inhibition of bacterial attachment by unknown factors in the skin mucus (Kawai and Kusuda, 1995). 

---