Tackling antibiotic resistance by inducing transient and robust collateral sensitivity

Area of Science:

• Microbiology
• Evolutionary Biology
• Pharmacology

Background:

• Collateral sensitivity (CS) is an evolutionary trade-off linked to antibiotic resistance (AR).
• The potential for transient, non-inherited CS induced by temporary AR has not been explored.
• Mutational AR in Pseudomonas aeruginosa can lead to CS, particularly with efflux pump overproduction.

Purpose of the Study:

• To investigate if transiently induced AR can cause non-inherited CS.
• To explore the potential of using transient CS to combat antibiotic-resistant infections.

Main Methods:

• Inducing transient ciprofloxacin resistance using dequalinium chloride in Pseudomonas aeruginosa.
• Assessing tobramycin collateral sensitivity in antibiotic-resistant mutants and clinical isolates.
• Evaluating the combined effect of tobramycin and dequalinium chloride on bacterial populations.

Main Results:

• Induction of transient AR via dequalinium chloride resulted in tobramycin CS.
• This transient CS was observed in various antibiotic-resistant strains, including those resistant to tobramycin.
• Combining tobramycin with dequalinium chloride led to the extinction of these bacterial strains.

Conclusions:

• Transiently induced AR can lead to non-inherited collateral sensitivity.
• This phenomenon offers a potential strategy for developing new treatments against antibiotic-resistant infections.
• Targeting transient CS may circumvent the evolution of inherited AR.