Draft genome sequence of reduced teicoplanin-susceptible and vancomycin-heteroresistant methicillin-resistant...

Area of Science:

• Microbiology
• Genomics
• Infectious Diseases

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global health threat.
• Emerging resistance to last-resort antibiotics like vancomycin in MRSA necessitates urgent investigation.
• Understanding the genetic basis of reduced vancomycin susceptibility is crucial for effective treatment strategies.

Purpose of the Study:

• To perform whole-genome sequencing on MRSA strains exhibiting reduced susceptibility to vancomycin and teicoplanin.
• To identify specific genetic mutations associated with this reduced antibiotic susceptibility.
• To characterize the predominant MRSA clones circulating in the Indian community setting.

Main Methods:

• Whole-genome shotgun sequencing was employed to analyze six MRSA isolates.
• Genomic data was analyzed to identify specific mutations in relevant genes and operons.
• MRSA strain typing was performed to determine clonal lineages.

Main Results:

• The Indian community-acquired MRSA (CA-MRSA) clone ST772-MRSA-V-t657 was identified in 50% of the isolates.
• Other identified clones included ST672-MRSA-IV (33%) and ST22-MRSA-IV (17%).
• Mutations were consistently found in the tcaRAB operon, vraSR, graSR, and/or rpoB genes, known determinants of heteroresistant vancomycin-intermediate S. aureus (hVISA) phenotype.

Conclusions:

• The study identified specific genetic mutations in key regulatory genes as potential drivers of reduced vancomycin and teicoplanin susceptibility in MRSA.
• The prevalence of ST772-MRSA-V-t657 highlights its significance as a concerning clone in the Indian context.
• These findings contribute to understanding the molecular mechanisms underlying vancomycin resistance in MRSA.