Single-nucleotide polymorphisms in a vancomycin-resistant Staphylococcus aureus strain based on whole-genome...

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Emergence of vancomycin-resistant Staphylococcus aureus (VRSA) poses a significant global health threat.
• Mechanisms of VRSA, particularly those not involving vanA gene acquisition, remain incompletely understood.

Purpose of the Study:

• To elucidate the mechanism of vancomycin resistance in VRSA strains lacking the vanA gene.
• To investigate genetic variations and phenotypic changes associated with acquired vancomycin resistance.

Main Methods:

• In vitro induction of vancomycin resistance in Staphylococcus aureus (strain V036) to generate resistant strain (V036-V64).
• Phenotypic characterization, including cell wall thickness and antibiotic susceptibility profiling.
• Whole-genome sequencing and single-nucleotide polymorphism (SNP) analysis to identify genetic differences.

Main Results:

• The resistant strain (V036-V64) exhibited a twofold thicker cell wall compared to the susceptible strain (V036).
• Reduced susceptibility to daptomycin and telavancin was observed in V036-V64, while susceptibility to linezolid, rifampicin, and ceftaroline remained similar.
• Eight SNPs were identified in V036-V64, including mutations in genes involved in cell wall synthesis (e.g., walK, D-alanyl-D-alanine carboxypeptidase, vraT).

Conclusions:

• Accumulation of mutations in cell wall synthesis-related genes can lead to increased cell wall thickness and high vancomycin resistance in S. aureus.
• This study highlights a novel vanA-negative mechanism contributing to the emergence of VRSA.
• Understanding these alternative resistance pathways is crucial for combating the spread of VRSA.