Assessment of antivirulence activity of several d-amino acids against Acinetobacter baumannii and Pseudomonas aeruginosa.
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.



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.



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.



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.
Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Complejo Hospitalario Universitario A Coruña (CHUAC) As Xubias, 15006 A Coruña, Spain.
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Rumbo
Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Complejo Hospitalario Universitario A Coruña (CHUAC) As Xubias, 15006 A Coruña, Spain.
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Vallejo
Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Complejo Hospitalario Universitario A Coruña (CHUAC) As Xubias, 15006 A Coruña, Spain.
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Cabral
Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Complejo Hospitalario Universitario A Coruña (CHUAC) As Xubias, 15006 A Coruña, Spain.
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Martínez-Guitián
Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Complejo Hospitalario Universitario A Coruña (CHUAC) As Xubias, 15006 A Coruña, Spain.
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Pérez
Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Complejo Hospitalario Universitario A Coruña (CHUAC) As Xubias, 15006 A Coruña, Spain.
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Beceiro
Servicio de Microbiología-Instituto de Investigación Biomédica (INIBIC), Complejo Hospitalario Universitario A Coruña (CHUAC) As Xubias, 15006 A Coruña, Spain german.bou.arevalo@sergas.es.
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D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000472:pathogenicity* / Q000502:physiology; D000596:Amino Acids / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000254:growth & development; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity* / Q000502:physiology; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D016019:Survival Analysis; D014774:Virulence / Q000187:drug effects
D000596:Amino Acids