NO signals for dispersing biofilms in clinical and industrial applications
A story from science bench to bedside, or at least towards it… What started as purely academic studies of the life cycle of bacterial biofilms, addressing the regulation of cell death events during late developmental stages, led to the discovery of a role for nitric oxide (NO) as a key regulator of biofilm dispersal. NO, which is a simple gas and universal biological signal, was found to be produced endogenously in mature biofilms, and trigger a signaling pathway involving the secondary messenger cyclic di-GMP, which in turn activates cellular effectors resulting in dispersal. Add-back of low levels (picomolar to nanomolar range) of NO was able to induce dispersal across various single species and mixed species biofilms. While the biofilm mode of growth confers a high level of resistance to control measures including antibiotics, exposure to NO greatly increases the efficacy of a range of antimicrobial treatments. Therefore the use of low, non-toxic concentrations of NO represents a promising strategy for the management of biofilms in medical and industrial contexts. Several NO-based technologies have been developed to control bacterial biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel materials and surface coatings which catalytically produce NO in situ, and (iii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments.