title: Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and have anti-mutagenic properties.
abstract: Cyclic dipeptides are known to have antiviral, antibiotic and antitumour properties. The aim of this study was to determine the combined effects of cyclo(L-leucyl-L-prolyl) and cyclo(L-phenylalanyl-L-prolyl) on the growth of vancomycin-resistant enterococci (VRE) and pathogenic yeasts, as well as determining their anti-mutagenic effects. This drug combination was especially effective against five VRE strains: Enterococcus faecium (K-99-38), E. faecalis (K-99-17), E. faecalis (K-99-258), E. faecium (K-01-312) and E. faecalis (K-01-511) with MIC values of 0.25-1 mg/l. It was also effective against Escherichia coli, Staphylococcus aureus, Micrococcus luteus, Candida albicans and Cryptococcus neoformans with MIC values of 0.25-0.5 mg/l. In addition, the cyclic dipeptides exerted anti-mutagenic activity against Salmonella typhimurium TA98 and TA100 strains in a Salmonella mutation assay. The number of mutant colonies of S. typhimurium strains TA98 and TA100 induced by exposure to AF-2 (0.2 microg/plate) decreased in a concentration-dependent manner in the presence of the two cyclic dipeptides (correlation 0.72 and 0.78, respectively). Here, for the first time, we report synergistic effects of the cyclic dipeptides [cyclo(L-leu-L-pro) and cyclo(L-phe-L-pro)] in inhibiting the growth of pathogenic microorganisms, as well as their anti-mutagenic effects in Salmonella strains.
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, # 300-6174 University Blvd., Vancouver, BC, Canada V6T 1Z3. howardr@interchange.ubc.ca
authors.forename: Ki-Hyeong
authors.initials: KH
authors.lastname: Rhee
mesh_terms: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D016587:Antimutagenic Agents; D010456:Peptides, Cyclic