Pleiotropic cellular responses underlying antibiotic tolerance in Campylobacter jejuni

Area of Science:

• Microbiology
• Molecular Biology
• Public Health

Background:

• Antibiotic tolerance allows susceptible bacteria to survive high antibiotic concentrations, posing a public health challenge.
• The molecular mechanisms driving antibiotic tolerance in bacteria remain largely unknown.
• Campylobacter jejuni is known to develop tolerance to antibiotics like ciprofloxacin and tetracycline.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying antibiotic tolerance in Campylobacter jejuni.
• To identify specific cellular responses and genes involved in C. jejuni's antibiotic tolerance.
• To investigate the role of identified genes in bacterial survival during antibiotic exposure.

Main Methods:

• RNA sequencing was performed on C. jejuni cultures exposed to ciprofloxacin or tetracycline to induce antibiotic tolerance.
• Gene expression profiles were analyzed to identify significantly upregulated genes.
• Knockout mutants were created for key genes to assess their role in antibiotic tolerance.

Main Results:

• Genes associated with protein chaperones, motility, DNA repair, drug efflux, and iron homeostasis were significantly upregulated during antibiotic tolerance.
• Mutants lacking these upregulated genes showed significantly reduced viability under antibiotic stress.
• Protein chaperone mutants exhibited increased protein aggregation, highlighting their role in managing cellular stress.

Conclusions:

• Multiple cellular defense mechanisms, including protein chaperones, DNA repair, and efflux pumps, collectively contribute to antibiotic tolerance in C. jejuni.
• Protein chaperones are critical for preventing protein aggregation and ensuring bacterial survival during antibiotic exposure.
• Understanding these mechanisms provides novel insights into combating antibiotic tolerance in bacterial pathogens.