Vancomycin resistance in Streptomyces coelicolor is phosphate-dependent but is not mediated by the PhoP regulator

Vancomycin is an essential antibiotic to treat infections caused by multidrug-resistant bacteria. Several bacteria show resistance to vancomycin, including the model actinomycete Streptomyces coelicolor. In this study, vancomycin disk diffusion tests were performed to determine vancomycin resistance in S. coelicolor M145 under rich (TSA medium) or defined (MMCGT medium) growth conditions. A vancomycin-susceptible phenotype was observed when the TSA rich medium was used, whereas a resistant phenotype was obtained when the low-phosphate MMCGT medium was used. To identify which component was responsible for the vancomycin-resistant phenotype, all the components of the MMCGT medium were added individually to the TSA medium, and vice versa. Addition of phosphate to the MMCGT medium (the phosphate concentration is much higher in TSA than in MMCGT) produced a vancomycin-susceptible phenotype in MMCGT. Phosphate regulation of vancomycin resistance is not PhoP-dependent since the same minimum inhibitory concentrations were obtained in S. coelicolor parental and ΔphoP mutant strains. This phosphate regulation was not observed in the vancomycin-producer Amycolatopsis orientalis NRRL 2452, which was always resistant both in TSA and MMCGT (with or without phosphate addition) media. On the other hand, other Streptomyces spp. were susceptible to vancomycin in all conditions tested, including Streptomyces toyocaensis, the producer of a glycopeptide antibiotic different from vancomycin. In conclusion, the phosphate concentration clearly affects the resistance of S. coelicolor to vancomycin.