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

Matthew V X Whelan,Chie Nakajima,Kentaro Koide,Tadhg Ó Cróinín,Jeremy C Simpson,Yasuhiko Suzuki,Laura Ardill

doi:10.1038/s41598-019-54620-1

Matthew V X Whelan, Chie Nakajima + Show 5 more

Open Access

https://doi.org/10.1038/s41598-019-54620-1

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Journal: Scientific Reports	Publication Date: Dec 1, 2019
Citations: 25	License type: open-access

Affiliation: University College Dublin, Hokkaido University

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.

Highlights

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
Fluoroquinolones work by inhibiting the function of the DNA Gyrase heterodimer GyrAB and high level fluoroquinolone resistance can be obtained by acquisition of a single point mutation in the QRDR region within the gyrA gene of C. jejuni[11,12,13]
To date no mutations in the gyrB gene have been associated with fluoroquinolone resistance in C. jejuni and the CmeABC multidrug efflux system has been implicated in intrinsic resistance to fluoroquinolones, mutations in this system have been reported to lead to an increase in fluoroquinolone susceptibility[14,15,16]

Summary

Introduction

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. We 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. The increased incedence of fluoroquinolone resistant strains of C. jejuni isolated from chicken meat even in countries which do not allow for large scale use of these antibiotics in livestock suggests that resistance to fluoroquinolones may confer a transmission advantage to C. jejuni beyond protection from antibiotics Together, these observations raise the prospect that resistance to fluoroquinolone antibiotics affects DNA supercoiling in a way that could lead to changes in virulent phenotypes and could possibly affect the ability of the bacteria to survive in the external environment

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