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 μg/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.