Abstract
The use of nitric oxide (NO) is emerging as a promising, novel approach for the treatment of antibiotic resistant bacteria and biofilm infections. Depending on the concentration, NO can induce biofilm dispersal, increase bacteria susceptibility to antibiotic treatment, and induce cell damage or cell death via the formation of reactive oxygen or reactive nitrogen species. The use of NO is, however, limited by its reactivity, which can affect NO delivery to its target site and result in off-target effects. To overcome these issues, and enable spatial or temporal control over NO release, various strategies for the design of NO-releasing materials, including the incorporation of photo-activable, charge-switchable, or bacteria-targeting groups, have been developed. Other strategies have focused on increased NO storage and delivery by encapsulation or conjugation of NO donors within a single polymeric framework. This review compiles recent developments in NO drugs and NO-releasing materials designed for applications in antimicrobial or anti-biofilm treatment and discusses limitations and variability in biological responses in response to the use of NO for bacterial eradiation.
Highlights
The development of antibiotic resistance, especially in ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), is considered to be one of the most pressing global health threats by the WHO
We summarize the current state of the art with respect to nitric oxide (NO)-delivery or releasing small molecules or macromolecular scaffolds for antibacterial or antibiofilm treatment
NO can improve the killing of both biofilm and planktonic P. aeruginosa, Listeria monocytogenes, S. aureus, B. cepacia, and other drug-resistant strains when used with various classes of antibiotics, such as macrolides, fluoroquinolone, β-lactam drugs, cephalosporins, polycationic peptides, and aminoglycosides, as well as other antimicrobial agents such as gallium (III) and antimicrobial peptides [32,44,45,46,47,48]
Summary
The development of antibiotic resistance, especially in ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), is considered to be one of the most pressing global health threats by the WHO. Biofilm formation in industrial pipelines, wastewater treatment facilities, cooling towers, and water distribution systems, as well as on ship hulls is a major problem [4,5] These issues necessitate the need to develop new methods to eradicate both planktonic and biofilm. Side effects/toxicity caused by the drug delivery therapeutic dose at the target site vehicle needs to be further evaluated. Depending on kinetics of NO release, targeted NO spontaneously released release may enable local NO concentrations to reach Side effects/toxicity caused by the low NO concentrations required for biofilm dispersal drug delivery vehicle needs to be. Side effects/toxicity caused by the drug delivery vehicle needs to be further evaluated
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