Acquisition of fluoroquinolone resistance leads to increased biofilm formation and pathogenicity in Campylobacter jejuni.

Matthew V X Whelan, Laura Ardill, Kentaro Koide, Chie Nakajima, Yasuhiko Suzuki, Jeremy C Simpson, Tadhg Ó Cróinín
Author Information
  1. Matthew V X Whelan: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.
  2. Laura Ardill: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.
  3. Kentaro Koide: Division of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
  4. Chie Nakajima: Division of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
  5. Yasuhiko Suzuki: Division of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan. ORCID
  6. Jeremy C Simpson: School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland. ORCID
  7. Tadhg Ó Cróinín: School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland. Tadhg.OCroinin@ucd.ie. ORCID

Abstract

The World Health Organization has listed C. jejuni as one of 12 microorganisms on a global priority list for antibiotic resistance due to a rapid increase in strains resistant to fluoroquinolone antibiotics. This fluoroquinolone resistance is conferred through a single point mutation in the QRDR region within the gyrA gene known to be involved in DNA supercoiling. We have previously revealed that changes in DNA supercoilikng play a major role in the regulation of virulence in C. jejuni with relaxation of DNA supercoiling associated with increased attachment to and invasion of human epithelial cells. The aim of this study was to investigate whether fluoroquinolone resistant strains of C. jejuni displayed altered supercoiling associated phenotypes. A panel of fluoroquinolone resistant mutants were derived and shown to have a greater ability to form viable biofilms under aerobic conditions, invade epithelial cells and promote virulence in the Galleria mellonella model of infection. We thus report for the first time that fluoroquinolone resistance in C. jejuni is associated with an increase in virulence and the ability to form viable biofilms in oxygen rich environments. These altered phenotypes likely play a critical role in the continued increase in fluoroquinolone resistance observed for this important pathogen.

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Grants

  1. 105343/Z/14/Z/Wellcome Trust (Wellcome)

MeSH Term

Biofilms
Campylobacter Infections
Campylobacter jejuni
DNA Gyrase
DNA, Superhelical
Drug Resistance, Bacterial
Fluoroquinolones
HT29 Cells
Humans
Microbial Sensitivity Tests
Point Mutation
Virulence

Chemicals

DNA, Superhelical
Fluoroquinolones
DNA Gyrase

Word Cloud

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