Overview of the effects and mechanisms of NO and its donors on biofilms.

Microbial biofilm is undoubtedly a challenging problem in the food industry. It is closely associated with human health and life, being difficult to remove and antibiotic resistance. Therefore, an alternate method to solve these problems is needed. Nitric oxide (NO) as an antimicrobial agent, has shown great potential to disrupt biofilms. However, the extremely short half-life of NO in vivo (2 s) has facilitated the development of relatively more stable NO donors. Recent studies reported that NO could permeate biofilms, causing damage to cellular biomacromolecules, inducing biofilm dispersion by quorum sensing (QS) pathway and reducing intracellular bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) levels, and significantly improving the bactericidal effect without drug resistance. In this review, biofilm hazards and formation processes are presented, and the characteristics and inhibitory effects of NO donors are carefully discussed, with an emphasis on the possible mechanisms of NO resistance to biofilms and some advanced approaches concerning the remediation of NO donor deficiencies. Moreover, the future perspectives, challenges, and limitations of NO donors were summarized comprehensively. On the whole, this review aims to provide the application prospects of NO and its donors in the food industry and to make reliable choices based on these available research results.