Sequencing of genomic DNA from three Streptomyces strains - 3C, R10 and R2. SNP identification performed against the reference genome from S. coelicolor A3(2).

Streptomyces coelicolor has innate and acquired resistance to multiple antibiotics. However mutations in two genes, ppm1 encoding a polyprenol phosphate mannose synthase, and pmt encoding a protein mannosyl transferase can confer antibiotic hyper-susceptibility, particularly to those that act at the cell wall. To gain insight into the mechanism(s) through which the pmt and ppm1 mutants have gained their pleiotropic phenotypes, we isolated second site suppressors of the vancomycin hyper-susceptibility. Genome resequencing of one of these suppressors and further genetic analyses showed that a common mechanism for regaining vancomycin resistance in a ppm1- strain is to acquire mutations in an operon, the sco2594 operon, containing three genes, sco2594-sco2593-sco2592 which possibly encode enzymes that synthesise an envelope polymer. Our hypothesis is that a putative polymer synthesized by the sco2594 operon attenuates vancomycin resistance in S. coelicolor.