Evolution under vancomycin selection drives divergent collateral sensitivity patterns in Staphylococcus aureus

Area of Science:

• Microbiology
• Evolutionary Biology
• Infectious Diseases

Background:

• Staphylococcus aureus infections are serious and often treated empirically with vancomycin.
• Current susceptibility testing may not predict drug efficacy during evolving infections.
• Antibiotic resistance development is a significant clinical challenge.

Purpose of the Study:

• To investigate how Staphylococcus aureus antibiotic susceptibility changes during vancomycin treatment.
• To understand the evolutionary mechanisms driving resistance.
• To inform therapeutic strategies by accounting for evolutionary dynamics.

Main Methods:

• Evolved methicillin-susceptible S. aureus (MSSA) populations under increasing vancomycin concentrations.
• Analyzed genetic mutations using sequencing.
• Assessed cross-resistance to other antibiotics (daptomycin, meropenem, gentamicin, nafcillin).
• Developed probabilistic models for drug response likelihood.

Main Results:

• Parallel mutations affecting cell membrane and cell wall were observed.
• Populations developed cross-resistance to daptomycin and varied responses to other antibiotics.
• Evolutionary trajectories introduced uncertainty in predicting treatment outcomes.
• Probabilistic likelihood estimates were derived to quantify drug response variability.

Conclusions:

• Vancomycin treatment can induce resistance and alter susceptibility to other drugs in S. aureus.
• Antistaphylococcal penicillins may be preferable first-line treatments for MSSA.
• Therapeutic choices should consider the probabilistic nature of bacterial evolution during infection.