The evolution of vancomycin intermediate Staphylococcus aureus (VISA) and heterogenous-VISA

Area of Science:

• Microbiology
• Genetics
• Evolutionary Biology

Background:

• Staphylococcus aureus rapidly develops resistance to new antimicrobials.
• Vancomycin resistance, observed as vancomycin-intermediate S. aureus (VISA) and heterogenous-VISA (hVISA), emerged decades after vancomycin's clinical release.
• Understanding the genetic and cell wall alterations driving vancomycin resistance in S. aureus is complex.

Purpose of the Study:

• To review the current understanding of the evolutionary process in the generation of hVISA and VISA.
• To explore the diverse genetic and cellular changes associated with vancomycin resistance in S. aureus.
• To highlight how these changes contribute to bacterial persistence.

Main Methods:

• Whole-genome sequencing to identify chromosomal changes linked to resistance.
• Analysis of mutations in key staphylococcal regulatory genes (e.g., walKR, graRS, vraSR, rpoB).
• Transcriptomics studies and host-pathogen interaction analyses.

Main Results:

• Diverse mutations in regulatory genes are associated with hVISA and VISA phenotypes.
• The evolution of VISA from vancomycin-susceptible S. aureus (VSSA) is a stepwise process.
• hVISA and VISA strains show altered metabolism, virulence factors, and susceptibility to host immunity and other antibiotics, favoring persistence.

Conclusions:

• hVISA and VISA represent an evolutionary adaptation for bacterial persistence.
• Genetic mutations in regulatory genes are crucial for developing vancomycin resistance.
• The study of vancomycin resistance has significantly advanced our understanding of staphylococcal biology.