D-amino acids enhance the activity of antimicrobials against biofilms of clinical wound isolates of Staphylococcus aureus and Pseudomonas aeruginosa.
Within wounds, microorganisms predominantly exist as biofilms. Biofilms are associated with chronic infections and represent a tremendous clinical challenge. As antibiotics are often ineffective against biofilms, use of dispersal agents as adjunctive, topical therapies for the treatment of wound infections involving biofilms has gained interest. We evaluated in vitro the dispersive activity of D-amino acids (D-AAs) on biofilms from clinical wound isolates of Staphylococcus aureus and Pseudomonas aeruginosa; moreover, we determined whether combinations of D-AAs and antibiotics (clindamycin, cefazolin, oxacillin, rifampin, and vancomycin for S. aureus and amikacin, colistin, ciprofloxacin, imipenem, and ceftazidime for P. aeruginosa) enhance activity against biofilms. D-Met, D-Phe, and D-Trp at concentrations of ≥ 5 mM effectively dispersed preformed biofilms of S. aureus and P. aeruginosa clinical isolates, an effect that was enhanced when they were combined as an equimolar mixture (D-Met/D-Phe/D-Trp). When combined with D-AAs, the activity of rifampin was significantly enhanced against biofilms of clinical isolates of S. aureus, as indicated by a reduction in the minimum biofilm inhibitory concentration (MBIC) (from 32 to 8 μg/ml) and a >2-log reduction of viable biofilm bacteria compared to treatment with antibiotic alone. The addition of D-AAs was also observed to enhance the activity of colistin and ciprofloxacin against biofilms of P. aeruginosa, reducing the observed MBIC and the number of viable bacteria by >2 logs and 1 log at 64 and 32 μg/ml in contrast to antibiotics alone. These findings indicate that the biofilm dispersal activity of D-AAs may represent an effective strategy, in combination with antimicrobials, to release bacteria from biofilms, subsequently enhancing antimicrobial activity.
United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Fort Sam Houston, Texas, USA carlos.j.sanchez47.vol@mail.mil.
Carlos J
CJ
Sanchez
United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Fort Sam Houston, Texas, USA Infectious Disease Service, Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, USA.
Kevin S
KS
Akers
United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Fort Sam Houston, Texas, USA.
Desiree R
DR
Romano
United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Fort Sam Houston, Texas, USA.
Ronald L
RL
Woodbury
United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Fort Sam Houston, Texas, USA.
Sharanda K
SK
Hardy
Infectious Disease Service, Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, USA.
Clinton K
CK
Murray
United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Fort Sam Houston, Texas, USA.
Joseph C
JC
Wenke
D000596:Amino Acids / Q000494:pharmacology*; D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002981:Clindamycin / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D013501:Surface-Active Agents / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology; D014947:Wounds and Injuries / Q000188:drug therapy / Q000382:microbiology; D047090:beta-Lactams / Q000494:pharmacology
D000596:Amino Acids; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D013501:Surface-Active Agents; D047090:beta-Lactams; D002981:Clindamycin; D014640:Vancomycin