TY - JOUR

T1 - Adaptive Laboratory Evolution of Staphylococcus aureus Resistance to Vancomycin and Daptomycin: Mutation Patterns and Cross-Resistance

AU - Гостев, В.В.

AU - Калиногорская, О.С.

AU - Сопова, Юлия Викторовна

AU - Сулян, Офелия Спартаковна

AU - Чулкова, Полина Сергеевна

AU - Велижанина, Мария Евгеньевна

AU - Цветкова, И.А.

AU - Агеевец, Владимир Андреевич

AU - Сидоренко, С.В.

PY - 2023/5/18

Y1 - 2023/5/18

N2 - 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.

AB - 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.

KW - MRSA

KW - Staphylococcus aureus

KW - VISA

KW - daptomycin

KW - glycopeptides

KW - hVISA

KW - in vitro resistance selection

KW - lipoglycopepdies

KW - vancomycin

UR - https://www.mendeley.com/catalogue/86ecee4b-ba89-3193-8831-f18411506f26/

U2 - 10.3390/antibiotics12050928

DO - 10.3390/antibiotics12050928

M3 - Article

C2 - 37237831

VL - 12

JO - Antibiotics

JF - Antibiotics

SN - 2079-6382

IS - 5

M1 - 928

ER -