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

Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant (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...

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Published in:Antibiotics (Basel) 2023-05, Vol.12 (5), p.928
Main Authors: Gostev, Vladimir, Kalinogorskaya, Olga, Sopova, Julia, Sulian, Ofelia, Chulkova, Polina, Velizhanina, Maria, Tsvetkova, Irina, Ageevets, Irina, Ageevets, Vladimir, Sidorenko, Sergey
Format: Article
Language:English
Subjects:
Antibiotics
Autolysis
Bacteremia
Biosynthesis
Cell walls
Cross-resistance
Daptomycin
Drug resistance
Evolution
Gene sequencing
Genes
Genomes
Glycerol
Growth rate
in vitro resistance selection
Metabolism
Methicillin
MRSA
Mutation
Oritavancin
Phospholipids
Population studies
Staphylococcus aureus
Staphylococcus infections
Vancomycin
VISA
Whole genome sequencing
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Summary:Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant (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 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 and were detected in derivatives selected for both antibiotics.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics12050928