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Antimicrobial Agents and Chemotherapy, November 2003, p. 3519-3524, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3519-3524.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Tylosin Resistance in Arcanobacterium pyogenes Is Encoded by an Erm X Determinant

B. Helen Jost,* Adam C. Field, Hien T. Trinh, J. Glenn Songer, and Stephen J. Billington

Department of Veterinary Science and Microbiology, The University of Arizona, Tucson, Arizona 85721

Received 4 April 2003/ Returned for modification 11 June 2003/ Accepted 22 July 2003

Arcanobacterium pyogenes, a commensal on the mucous membranes of many economically important animal species, is also a pathogen, causing abscesses of the skin, joints, and visceral organs as well as mastitis and abortion. In food animals, A. pyogenes is exposed to antimicrobial agents used for growth promotion, prophylaxis, and therapy, notably tylosin, a macrolide antibiotic used extensively for the prevention of liver abscessation in feedlot cattle in the United States. Of 48 A. pyogenes isolates, 11 (22.9%) exhibited inducible or constitutive resistance to tylosin (MIC of >=128 µg/ml). These isolates also exhibited resistance to other macrolide and lincosamide antibiotics, suggesting a macrolide-lincosamide resistance phenotype. Of the 11 resistant isolates, genomic DNA from nine hybridized to an erm(X)-specific probe. Cloning and nucleotide sequencing of the A. pyogenes erm(X) gene indicated that it was >95% similar to erm(X) genes from Corynebacterium and Propionibacterium spp. Eight of the erm(X)-containing A. pyogenes isolates exhibited inducible tylosin resistance, which was consistent with the presence of a putative leader peptide upstream of the erm(X) open reading frame. For at least one A. pyogenes isolate, 98-4277-2, erm(X) was present on a plasmid, pAP2, and was associated with the insertion sequence IS6100. pAP2 also carried genes encoding the repressor-regulated tetracycline efflux system determinant Tet 33. The repA gene from pAP2 was nonfunctional in Escherichia coli and at least one A. pyogenes isolate, suggesting that there may be host-encoded factors required for replication of this plasmid.

* Corresponding author. Mailing address: Department of Veterinary Science and Microbiology, The University of Arizona, 1117 East Lowell St., Tucson, AZ 85721. Phone: (520) 621 2745. Fax: (520) 621 6366. E-mail: jost{at}u.arizona.edu.

Antimicrobial Agents and Chemotherapy, November 2003, p. 3519-3524, Vol. 47, No. 11
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.11.3519-3524.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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