Genome Comparison of Erythromycin Resistant Campylobacter from Turkeys Identifies Hosts and Pathways for Horizontal Spread of erm(B) Genes

Abstract

Pathogens in the genus Campylobacter are the most common cause of food-borne bacterial gastro-enteritis. Campylobacteriosis, caused principally by Campylobacter jejuni and Campylobacter coli, is transmitted to humans by food of animal origin, especially poultry. As for many pathogens, antimicrobial resistance in Campylobacter is increasing at an alarming rate. Erythromycin prescription is the treatment of choice for clinical cases requiring antimicrobial therapy but this is compromised by mobility of the erythromycin resistance gene erm(B) between strains. Here, we evaluate resistance to six antimicrobials in 170 Campylobacter isolates (133 C. coli and 37 C. jejuni) from turkeys. Erythromycin resistant isolates (n = 85; 81 C. coli and 4 C. jejuni) were screened for the presence of the erm(B) gene, that has not previously been identified in isolates from turkeys. The genomes of two positive C. coli isolates were sequenced and in both isolates the erm(B) gene clustered with resistance determinants against aminoglycosides plus tetracycline, including aad9, aadE, aph(2″)-IIIa, aph(3')-IIIa, and tet(O) genes. Comparative genomic analysis identified identical erm(B) sequences among Campylobacter from turkeys, Streptococcus suis from pigs and Enterococcus faecium and Clostridium difficile from humans. This is consistent with multiple horizontal transfer events among different bacterial species colonizing turkeys. This example highlights the potential for dissemination of antimicrobial resistance across bacterial species boundaries which may compromise their effectiveness in antimicrobial therapy.

Keywords: Campylobacter; antimicrobial; erm(B); erythromycin; transmission; turkey.

FIGURE 1

Comparative genetic organization of erm(B)-carrying genomic islands from Campylobacter coli ZTA14/01086 (this study), C. coli ZTA 14/01426 (this study) and previously identified C. coli ZTA09/02204 (17). Antimicrobial resistance genes are colored as follows: erm(B) gene (blue); aminoglycoside resistance genes (yellow); the tetracycline resistance gene tet(O) (purple). Genes with other predicted functions or encoding hypothetical proteins are shown in white. Gray shading indicates regions sharing 98% DNA identity.

FIGURE 2

Host and geographical distribution of the erm(B) alleles identified in Campylobacter in this study among other bacterial genera. Allele 1 belongs to C. coli ZTA14/01426 (MF134832), allele 2 belongs to C. coli ZTA09/02204 (KT953380), allele 3 belongs to C. coli ZTA14/01086 (MF134831) and allele 4 belongs to C. jejuni C179b (KF864551). erm(B) homologs were identified in GenBank using BLAST with a coverage and similarity of 100%. Accession numbers of each sequence is given in Supplementary Table S3. Sequences without host data and geographical location have not been included. Exact identity of erm(B) alleles between species, host/environment and origin of isolation is represented by a connection (width proportional to relative prevalence).