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Published on: March 28, 2017
Reduced susceptibility to vancomycin in isogenic Staphylococcus aureus strains of sequence type 59: tracking
Chih-Jung Chen1, Mei-Hui Lin, Jwu-Ching Shu
1Division of Paediatric Infectious Diseases, Department of Paediatrics, Chang Gung Children's Hospital and Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Objectives:
Vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) phenotypes are increasingly reported in methicillin-resistant S. aureus (MRSA) strains of distinct genetic backgrounds. This study tracked genetic evolution during the development of vancomycin non-susceptibility in a prevalent Asian community-associated MRSA clone of sequence type (ST) 59.
Methods:
ST59 strains were consecutively isolated from a patient who failed chemotherapy for a septic knee over 15 months. The genetic mutations associated with the VISA phenotype were identified by whole-genome sequencing of two strains, which had the vancomycin-susceptible S. aureus (VSSA) and VISA phenotypes. The mutations were subsequently screened in other strains. By correlating the accumulated mutations with vancomycin susceptibility, genetic evolution was tracked at the whole-genome scale.
Results:
Nine non-synonymous mutations and two steps of genetic evolution were identified during the development of the VISA phenotype. The first step involved a nonsense mutation in agrC and point mutations at five other loci, which were associated with the VSSA-to-hVISA conversion. Mutations of rpoB and fusA following the use of rifampicin and fusidic acid were identified in the second step of evolution, which corresponded to the development of dual resistance to rifampicin and fusidic acid and the conversion of hVISA to VISA.
Conclusions:
In vivo genetic evolution of S. aureus occurred in stepwise order during the development of incremental vancomycin non-susceptibility and was related to the use of antimicrobial agents.
Insights
Genetic evolution of vancomycin-intermediate Staphylococcus aureus (VISA) occurred in two steps, driven by antimicrobial use. This stepwise accumulation of mutations led to increased vancomycin non-susceptibility in methicillin-resistant S. aureus (MRSA) strains.
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- Vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are growing concerns in methicillin-resistant S. aureus (MRSA) infections.
- Understanding the genetic basis of vancomycin non-susceptibility is crucial for developing effective treatment strategies.
Purpose of the Study:
- To track the genetic evolution of vancomycin non-susceptibility in a prevalent Asian community-associated MRSA clone (ST 59).
- To identify specific genetic mutations associated with the development of VISA and hVISA phenotypes.
Main Methods:
- Whole-genome sequencing of vancomycin-susceptible S. aureus (VSSA) and VISA strains isolated from a patient over 15 months.
- Screening of identified mutations in other isolates to correlate genetic changes with vancomycin susceptibility.
- Tracking genetic evolution at the whole-genome scale by correlating accumulated mutations with susceptibility.
Main Results:
- Nine non-synonymous mutations and two distinct evolutionary steps were identified during VISA development.
- The initial step involved mutations in agrC and five other loci, leading to VSSA-to-hVISA conversion.
- The second step, associated with rifampicin and fusidic acid use, involved mutations in rpoB and fusA, resulting in dual resistance and hVISA-to-VISA conversion.
Conclusions:
- In vivo genetic evolution of S. aureus towards vancomycin non-susceptibility occurs in a stepwise manner.
- Antimicrobial agent use plays a significant role in driving this genetic evolution and the development of resistance.
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