Genomic characterization and antimicrobial resistance of Campylobacter
PhD Thesis defense by Diego Flórez Cuadrado at the Faculty of Veterinary Medicine of the Complutense University of Madrid
November 6th, 2017
Bacteria of the genus Campylobacter, mainly C. jejuni and C. coli, represent the most frequent cause of gastroenteritis of alimentary origin worldwide. These microorganisms colonize the digestive tract of birds and mammals. The main route of infection for humans is through the consumption of contaminated poultry meat. The infection produced by Campylobacter is usually self-limiting but can occasionally produce complications that require antimicrobial treatment. Erythromycin is the main treatment of choice.
Resistance to erythromycin in Campylobacter has been related to mutations in genes or ribosomal proteins, efflux pumps and more recently the presence of the erm(B) gene. This gene was originally identified in Campylobacter isolates from China and in all cases was located in genomic islands of multiresistance. The genomic islands identified in Campylobacter carry genes of resistance to different antimicrobials, which limits the therapeutic options.
In the present doctoral thesis, we characterized a collection of C. jejuni and C. coli isolates from food animals, humans and wastewater, with the aim to characterize them by MLST and identify antibiotic resistance genes and their association with multiresistance genomic islands. In addition, the metabolic profiles of isolates belonging to sequences types (STs) related with human campylobacteriosis were evaluated.
Regarding the polymorphism detected at genomic level, including virulence genes and metabolic profiles, the characterization of isolates showed that the gamma-glutamyltranspeptidase (ggt) gene, responsible for the expression of the enzyme that metabolizes glutamine, was significantly associated with ST-45 of C. jejuni. In addition, other genes involved in the metabolism of amino acids such as ansB(s), fucP and dmsA were differentially detected in isolates of C. jejuni ST-45, revealing the presence of five different metabolic profiles. The analysis of gene polymorphism showed an association between certain factors of colonization and certain STs, besides evidencing the different combinations of metabolic genes.
The study of macrolide resistance mechanisms in Campylobacter resulted in the first description in Europe of the erm(B) gene, associated with a genomic island of multiresistance in Campylobacter isolates. This mechanism of resistance was detected in C. coli isolates from broiler and turkey, with the genomic analysis indicating the diversity of these elements. The results suggest that the presence of the erm(B) gene in Campylobacter has its origin in grampositive bacteria and that the alleles identified in this study have been previously detected in pathogenic bacteria mainly from pigs and people in Asia and Europe. The arrangement of the different resistance genes and the sequences detected, point out to a wide mobility of these genetic elements.
Finally, other antibiotic resistance genes and their possible association with genomic multirresistance islands in C. jejuni and C. coli isolates were identified. Multiresistant isolates (resistant to three or more classes of antibiotics) were detected in animal, human and wastewater samples. In 18 Campylobacter isolates different genomic islands of multiresistance were identified, indicating the clustering of antibiotic resistance genes in the same DNA sequence. This study reveals that these genetic elements from Campylobacter are potential dispersion vehicles of antibiotic resistance genes.
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