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Title: 23S rRNA gene mutations contributing to macrolide resistance in Campylobacter jejuni and Campylobacter coli

Author
item Ladely, Scott
item Meinersmann, Richard - Rick
item Englen, Mark
item Cray, Paula
item HARRISON, MARK - UNIVERSITY OF GEORGIA

Submitted to: Foodborne Pathogens and Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/26/2008
Publication Date: 1/1/2009
Citation: Ladely, S.R., Meinersmann, R.J., Englen, M.D., Cray, P.J., Harrison, M.A. 2009. 23S rRNA gene mutations contributing to macrolide resistance in Campylobacter jejuni and Campylobacter coli. Foodborne Pathogens and Disease. 6(1):91-98.

Interpretive Summary: Campylobacter jejuni is a bacterial food-borne pathogen that is commonly responsible for diarrheal disease in humans. The disease does not usually require antimicrobial treatment, but when it does erythromycin is generally effective. Erythromycin is a member of the class of antimicrobials known as macrolides. Resistance to one macrolide is often associated with resistance to others. Tylosin is a macrolide that is used in food animals. Resistance occurs by a number of different mechanisms, one of which is by specific mutations to the ribosomal genes. Campylobacter has three copies of the ribosomal genes, but little is known about how many copies need to mutate in order for resistance to occur. This study was designed to identify the changes of each of the ribosomal genes associated with resistance to tylosin in a collection of Campylobacter jejuni and Campylobacter coli. A low level of resistance was found in some strains with no ribosomal gene changes. Very high level of resistance was found in several isolates when all three copies of the gene changed and two isolates with slightly less resistance had two copies of their ribosomal genes changed. An isolate with just one gene changed was never found, indicating that change of one copy of the ribosome can trigger the rapid change of at least the second copy of the gene and possibly the third as well. The change of at least two copies of the ribosome may be required for resistance to occur. Therefore, if exchange between copies of the ribosome can be prevented then resistance to macrolides may arise at a much lower rate.

Technical Abstract: Operon specific 23S rRNA mutations affecting minimum inhibitory concentrations (MICs) of macrolides (erythromycin [ERY], azithromycin [AZM], tylosin [TYL]) and a lincosamide (clindamycin [CLI]) were examined in a collection of Campylobacter jejuni and C. coli isolates. The three copies of the Campylobacter 23S rRNA gene were individually amplified by PCR. Sequence data for domain V showed that all five C. coli isolates expressing macrolide resistance exhibited A2059G transitions (E. coli numbering). One of the C. coli isolates exhibited the A2059G transition in only two of the three copies of the target gene. Two of the macrolide-resistant C. jejuni isolates, resistant to ERY only, had no 23S rRNA mutations. Among the nine other macrolide-resistant C. jejuni isolates, two different point mutations within domain V were observed. Three macrolide-resistant C. jejuni isolates had A2059G transitions. One of these three C. jejuni isolates had the A2059G transition in only two of the three copies. The six remaining macrolide-resistant C. jejuni isolates had an A2058C transversion in all three copies of the 23S rRNA gene. Campylobacter jejuni isolates with the A2058C transversion had higher ERY MICs (>256 ug/ml) compared to C. jejuni isolates with A2059G transitions (64-128 ug/ml). In addition, C. jejuni and C. coli isolates with only two copies of the 23S rRNA gene having A2059G substitutions had lower ERY, AZM, TYL, and CLI MICs compared to isolates with all three copies of the gene mutated. No isolates were observed having only one copy of the 23S rRNA gene with a mutation.