Mutations Associated with Reduced Surotomycin Susceptibility in Clostridium difficile and Enterococcus Species

摘要: Clostridium difficile infection (CDI) is an urgent public health concern causing considerable clinical and economic burdens. CDI can be treated with antibiotics, but recurrence of the disease following successful treatment initial episode often occurs. Surotomycin a rapidly bactericidal cyclic lipopeptide antibiotic that in trials for has demonstrated superiority over vancomycin preventing relapse. structural analogue membrane-active daptomycin. Previously, we utilized vitro serial passage experiments to derive C. strains reduced surotomycin susceptibilities. The parent used included ATCC 700057 isolates from restriction endonuclease analysis (REA) groups BI K. Serial were also performed vancomycin-resistant vancomycin-susceptible Enterococcus faecium faecalis. goal this study identify mutations associated susceptibility enterococci. Illumina sequence data generated compared. We identified nonsynonymous genes coding cardiolipin synthase 700057, enoyl-(acyl carrier protein) reductase II (FabK) cell division protein FtsH2 REA type BI, PadR family transcriptional regulator Among 4 enterococcal strain pairs, 20 identified, those overlap daptomycin resistance. These give insight into mechanism action against difficile, possible mechanisms resistance emergence during use, potential impacts therapy on intestinal