| Autor: |
Gostev V; Pediatric Research and Clinical Center for Infectious Diseases, Department of Medical Microbiology and Molecular Epidemiology, 197022 Saint Petersburg, Russia.; Department of Medical Microbiology, North-Western State Medical University named after I.I. Mechnikov, 195067 Saint Petersburg, Russia., Kalinogorskaya O; Pediatric Research and Clinical Center for Infectious Diseases, Department of Medical Microbiology and Molecular Epidemiology, 197022 Saint Petersburg, Russia., Sopova J; Center of Transgenesis and Genome Editing, Saint Petersburg State University, 199034 Saint Petersburg, Russia.; Saint Petersburg Branch of Vavilov Institute of General Genetics, Russian Academy of Sciences, 198504 Saint Petersburg, Russia., Sulian O; Pediatric Research and Clinical Center for Infectious Diseases, Department of Medical Microbiology and Molecular Epidemiology, 197022 Saint Petersburg, Russia., Chulkova P; Pediatric Research and Clinical Center for Infectious Diseases, Department of Medical Microbiology and Molecular Epidemiology, 197022 Saint Petersburg, Russia., Velizhanina M; Center of Transgenesis and Genome Editing, Saint Petersburg State University, 199034 Saint Petersburg, Russia.; Laboratory of Signal Regulation, All-Russia Research Institute for Agricultural Microbiology, Pushkin, 196608 Saint Petersburg, Russia., Tsvetkova I; Pediatric Research and Clinical Center for Infectious Diseases, Department of Medical Microbiology and Molecular Epidemiology, 197022 Saint Petersburg, Russia., Ageevets I; Pediatric Research and Clinical Center for Infectious Diseases, Department of Medical Microbiology and Molecular Epidemiology, 197022 Saint Petersburg, Russia., Ageevets V; Pediatric Research and Clinical Center for Infectious Diseases, Department of Medical Microbiology and Molecular Epidemiology, 197022 Saint Petersburg, Russia., Sidorenko S; Pediatric Research and Clinical Center for Infectious Diseases, Department of Medical Microbiology and Molecular Epidemiology, 197022 Saint Petersburg, Russia.; Department of Medical Microbiology, North-Western State Medical University named after I.I. Mechnikov, 195067 Saint Petersburg, Russia. |
| Abstrakt: |
Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections, including bacteremia. However, their effectiveness is limited not only by their resistance to each antibiotic but also by their associated resistance to both drugs. It is unknown whether novel lipoglycopeptides can overcome this associated resistance. Resistant derivatives from five S. aureus strains were obtained during adaptive laboratory evolution with vancomycin and daptomycin. Both parental and derivative strains were subjected to susceptibility testing, population analysis profiles, measurements of growth rate and autolytic activity, and whole-genome sequencing. Regardless of whether vancomycin or daptomycin was selected, most of the derivatives were characterized by a reduced susceptibility to daptomycin, vancomycin, telavancin, dalbavancin, and oritavancin. Resistance to induced autolysis was observed in all derivatives. Daptomycin resistance was associated with a significant reduction in growth rate. Resistance to vancomycin was mainly associated with mutations in the genes responsible for cell wall biosynthesis, and resistance to daptomycin was associated with mutations in the genes responsible for phospholipid biosynthesis and glycerol metabolism. However, mutations in walK and mprF were detected in derivatives selected for both antibiotics. |
