Abstract
Anthranilate, one of tryptophan degradation products has been reported to interfere with biofilm formation by Pseudomonas aeruginosa. Here, we investigated the effects of anthranilate on biofilm formation by various bacteria and the mechanisms responsible. Anthranilate commonly inhibited biofilm formation by P. aeruginosa, Vibrio vulnificus, Bacillus subtilis, Salmonella enterica serovar Typhimurium, and Staphylococcus aureus, and disrupted biofilms preformed by these bacteria. Because anthranilate reduced intracellular c-di-GMP and enhanced swimming and swarming motilities in P. aeruginosa, V. vulnificus, B. subtilis, and S. enterica, it is likely that anthranilate disrupts biofilms by inducing the dispersion of these bacteria. On the other hand, in S. aureus, a non-flagellate bacterium that has no c-di-GMP signaling, anthranilate probably inhibits biofilm formation by reducing slime production. These results suggest that anthranilate has multiple ways for biofilm inhibition. Furthermore, because of its good biofilm inhibitory effects and lack of cytotoxicity to human cells even at high concentration, anthranilate appears to be a promising agent for inhibiting biofilm formation by a broad range of bacteria.
Highlights
Biofilms are surface-attached microbial communities encapsulated in extracellular polymeric substances (EPS)[1, 2]
We selected five bacterial species, that is, P. aeruginosa, V. vulnificus, B. subtilis, S. enterica serovar Typhimurium, and S. aureus, because these strains represent a variety of bacteria in terms of their genetic classification, whether or not they produce anthranilates, type of motility, and their importance (Table S2)
Our results show the following: 1) anthranilate exerts biofilm-inhibiting effects on a wide range of bacteria; 2) in P. aeruginosa, V. vulnificus, B. subtilis, and S. enterica, anthranilate reduces intracellular c-di-GMP levels and enhances swarming and swimming motilities to induce biofilm dispersion; 3) in S. aureus, anthranilate reduces slime production to inhibit biofilm formation
Summary
Biofilms are surface-attached microbial communities encapsulated in extracellular polymeric substances (EPS)[1, 2]. Indole was found to enhance biofilm formation by P. aeruginosa in a quorum sensing (QS)-independent manner[21, 23] Some other bacteria, such as, P. aeruginosa, metabolize tryptophan to anthranilate through a kynurenine pathway using kynBAU genes[24]. It was reported in P. aeruginosa that anthranilate degradation is related to biofilm formation. It was found that anthranilate can disrupt biofilm structures and induce the detachment of preformed P. aeruginosa biofilms by reducing intracellular c-di-GMP levels and modulating the expressions of genes involved in EPS production[23] It remains unclear whether anthranilate affects biofilm formation by other microorganisms, despite its potent biofilm-inhibiting effects. We found that anthranilate disrupted biofilm formation by a wide range of bacteria and that it www.nature.com/scientificreports/
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