In vitro development of resistance to fosfomycin

Area of Science:

• Microbiology
• Bacterial Genetics
• Antimicrobial Resistance

Background:

• Fosfomycin is a crucial antibiotic used to treat various bacterial infections.
• Understanding the mechanisms of fosfomycin resistance is vital for effective antimicrobial therapy.
• High-frequency resistance development in vitro necessitates investigation into underlying genetic and cellular processes.

Purpose of the Study:

• To elucidate the mechanism and frequency of bacterial resistance development to fosfomycin.
• To investigate the origin of resistant colonies observed in fosfomycin inhibition zones.
• To characterize the intermediate steps in the emergence of fosfomycin resistance.

Main Methods:

• Utilized nutrient agar plates with fosfomycin filter discs to create zones of inhibition.
• Observed and characterized colony morphology within the zones of inhibition.
• Investigated the genetic basis of resistance, focusing on the fosfomycin transport system.
• Analyzed the mutational events leading to the development of resistant phenotypes.

Main Results:

• Resistant colonies frequently appeared within fosfomycin inhibition zones.
• Resistance was primarily attributed to the loss or dysfunction of the fosfomycin transport system.
• Small, translucent colonies emerged first within the inhibition zones.
• Subsequent mutational events within these translucent colonies led to the typical resistant colony type.

Conclusions:

• Bacterial resistance to fosfomycin often involves the loss of its specific transport system.
• The development of fosfomycin resistance is typically a multi-step process, not a direct mutational event.
• Intermediate translucent colony morphotypes play a critical role in the evolution of fosfomycin resistance.