Collateral Sensitivity to β-Lactam Antibiotics in Evolved Apramycin-Resistant MRSA

Area of Science:

• Microbiology
• Bacterial Resistance
• Antibiotic Discovery

Background:

• Collateral sensitivity is a phenomenon where resistance to one antibiotic confers sensitivity to another.
• Methicillin-resistant Staphylococcus aureus (MRSA) is a significant public health concern due to its resistance to common antibiotics.

Purpose of the Study:

• To investigate the collateral sensitivity of MRSA to beta-lactam antibiotics after developing resistance to apramycin.
• To understand the underlying mechanisms of this induced collateral sensitivity.

Main Methods:

• MRSA strains were exposed to increasing concentrations of apramycin to induce resistance.
• The resulting resistant strains were tested for sensitivity to a panel of beta-lactam antibiotics.
• Key molecular markers including beta-lactamase activity and mecA gene expression were analyzed.
• Cellular functions such as proton motive force and efflux activity were assessed.

Main Results:

• Acquisition of apramycin resistance in MRSA led to collateral sensitivity to multiple beta-lactam antibiotics (ampicillin, cephazolin, ceftriaxone, cefotaxime, cefepime, cefquinome).
• This sensitivity correlated with reduced beta-lactamase activity and decreased mecA gene expression.
• A decrease in proton motive force and reduced efflux pump activity were also observed.

Conclusions:

• Induced apramycin resistance in MRSA results in collateral sensitivity to beta-lactam antibiotics.
• The observed collateral sensitivity is linked to reduced beta-lactamase activity, lower mecA expression, diminished proton motive force, and decreased efflux.
• These findings highlight the potential of collateral sensitivity as a therapeutic strategy against MRSA.