Assessment of antivirulence activity of several d-amino acids against Acinetobacter baumannii and Pseudomonas aeruginosa. (7th September 2016)

• Record Type: Journal Article
• Authors: Rumbo, C.; Vallejo, J. A.; Cabral, M. P.; Martínez-Guitián, M.; Pérez, A.; Beceiro, A.; Bou, G.
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 71:Number 12(2016:Dec.)
• Page Start: 3473
• Page End: 3481
• Publication Date: 2016-09-07
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkw342
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract : Objectives: Biofilm formation and bacterial adherence are important requirements for persistence, multidrug resistance and infection. The d -amino acids play a role as modulators of bacterial growth and persistence, though their ability to inhibit biofilms is much debated. In this study, we analysed the effects of 18 different d -amino acids on the pathogens Acinetobacter baumannii and Pseudomonas aeruginosa . Methods: In vitro assays were carried out to analyse the effect of d -amino acids on bacterial growth, biofilm formation/disassembly, capacity to attach to eukaryotic cells and cellular death. In addition, in vivo assays were performed in mice, using experimental models of sepsis and pneumonia. Results: Biofilm formation was inhibited in A. baumannii by d -His, d -Cys and d -Trp (35%–86%) at 2 mM and in P. aeruginosa by d -Cys, d -Trp and d -Tyr (10%–30%) at 4 mM. Attachment to the A549 human alveolar cells was reduced in A. baumannii by d -Cys, d -His, d -Met, d -Val and d -Ser, and in P. aeruginosa by d -Arg and d -Trp. Growth was inhibited in A. baumannii by d -Cys and d -Trp, and in P. aeruginosa by d -Trp . In virulence assays, incubation of alveolar cells infected with P. aeruginosa with d -Cys, d -Trp and d -Arg reduced cell death (56%–45%). However, no significant effect of d -amino acids was observed in vivo . Conclusions: Some d -amino acids can inhibit bacterial growth, biofilm formation and adherence to eukaryotic cells in A. baumannii and P. aeruginosa, and showed a protective effect against infection of alveolar cells with P. aeruginosa . Despite the fact that some considerable protection was observed in mice, survival differences between treated and control groups were not statistically significant.