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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
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Key role of Mfd in the development of fluoroquinolone resistance in Campylobacter jejuni

Jing Han1, Orhan Sahin, Yi-Wen Barton

  • 1Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.

Plos Pathogens
|June 7, 2008
PubMed

Insights

The Mfd protein promotes the development of fluoroquinolone resistance in Campylobacter jejuni by increasing mutation rates. Inhibiting Mfd may reduce the emergence of antibiotic-resistant Campylobacter infections.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Campylobacter jejuni is a significant foodborne pathogen causing human enterocolitis.
  • Fluoroquinolone antibiotics are crucial for treating campylobacteriosis, but resistance is a growing concern.
  • Understanding resistance mechanisms is vital for effective treatment strategies.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying fluoroquinolone resistance in Campylobacter jejuni.
  • To identify specific genes and pathways involved in the development of antibiotic resistance.

Main Methods:

  • Comparative gene expression profiling of C. jejuni using DNA microarrays in the presence and absence of ciprofloxacin.
  • Mutation analysis of the mfd gene to assess its role in spontaneous mutation rates.
  • In vivo and in vitro studies evaluating the impact of mfd gene alterations on fluoroquinolone resistance development.

Main Results:

  • Ciprofloxacin significantly altered the expression of multiple genes in C. jejuni.
  • The mfd gene, encoding a transcription-repair coupling factor, was notably upregulated by ciprofloxacin.
  • Loss of mfd function reduced spontaneous mutation rates and fluoroquinolone resistance development in C. jejuni.
  • Overexpression of mfd increased mutation frequency, highlighting its role in promoting genetic variation.

Conclusions:

  • Mfd plays a critical role in the emergence of fluoroquinolone resistance in Campylobacter.
  • Mfd possesses a previously unrecognized function in elevating mutation frequencies.
  • Targeting Mfd presents a potential strategy to mitigate the spread of fluoroquinolone-resistant Campylobacter infections.

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