Impact of nitric oxide donors on capsule, biofilm and resistance profiles of Klebsiella pneumoniae

Klebsiella pneumoniae is considered to be a critical public health threat due to its ability to cause fatal, multi-drug-resistant infections in the bloodstream and key organs. The polysaccharide-based capsule layer that shields K. pneumoniae from clearance via innate immunity is a prominent virulence factor. K. pneumoniae also forms biofilms on biotic and abiotic surfaces. These biofilms significantly reduce penetration by, and antibacterial activity from, traditional antibiotics. Nitric oxide (NO), an endogenous molecule involved in the innate immune system, is equally effective at eradicating bacteria but without engendering resistance. This study investigated the effects of NO-releasing small molecules capable of diverse release kinetics on the capsule and biofilm formation characteristics of multiple K. pneumoniae strains. The use of NO donors with moderate and extended NO-release properties (i.e., half-life >1.8 h) inhibited bacterial growth. Additionally, treatment with NO decreased capsule mucoviscosity in K. pneumoniae strains that normally exhibit hypermucoviscosity. The NO donors were also effective against K. pneumoniae biofilms at the same minimum biocidal concentrations that eliminated planktonic bacteria, while meropenem showed little antibacterial action in the same experiments. These results represent the first account of exogenous NO affecting biomarkers involved in K. pneumoniae infections, and may therefore inform future development of NO-based therapeutics for treating such infections.