Journal of Antimicrobial Chemotherapy (2001) 47, 495-496
© 2001 The British Society for Antimicrobial Chemotherapy
Correspondence |
Current status of the aadA and dfr gene cassette families
Virology Division, Department of Microbiology, SEALS, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia
Sir,
Antibiotic-resistant microorganisms have significantly compromised antibiotic treatment. A large proportion of resistance in Gram-negative bacteria can be attributed to resistance gene cassettes contained within a site-specific recombination system, termed the integron.1 Mobile cassettes contain genes that confer resistance to nearly every major class of antibiotic and some disinfectants. New gene cassettes continue to be identified and the sequences of >60 cassettes are deposited in the DDBJ/EMBL/GenBank databases, as of November 2000. This rapid increase in the identification of gene cassettes has led to identical names being given to two different gene cassettes, or the incorrect naming of gene cassettes. This letter aims to clarify the current nomenclature for the aadA and dfr families of genes.
The aadA family of genes encode aminoglycoside-3''-adenylyltransferases (AAD), which confer resistance to streptomycin and spectinomycin by adenylylation. Until recently, only four members of this family were known, including aadA1a, aadA1b, aadA2 and aadA3. A further four gene cassettes have been described since 1999. The rapid emergence of these new cassettes has led to confusion in the nomenclature in both the DDBJ/EMBL/GenBank databases and the literature. In a recent publication by Chang et al.,2 a gene cassette with an identical sequence to aadA53,4 was assigned the name aadA4. The aadA4 name had already been assigned to the gene discovered by Adrian et al.5 The database entry for the aadA gene of Chang et al. has since been corrected to aadA5 (accession number AF170088). Recently discovered aadA genes with corresponding publications now include aadA4,5 aadA5,2–4 aadA66 and aadA7.7
Gene cassettes play a significant role in the resistance to trimethoprim of Gram-negative bacteria, with 15 of the 19 known transferable dihydrofolate reductases (DHFRs) encoded by genes that form part of a gene cassette.3 These genes encode two distinct types of enzyme and have therefore been divided into two families, A and B.8 In the past, Roman numerals have been used to number the dfrA genes; however, Arabic numbers have now superseded the Roman numbering system. The Table shows the current status of the dfr genes and their respective proteins. The type A gene family encode DHFRs of between 157 and 187 residues. Alignments of 17 of these enzymes reveal high conservation within the N termini of these proteins, with 12 residues strictly conserved across all enzymes. The second gene family, type B, (dfrB1, dfrB2 and dfrB3) all form part of a gene cassette, and encode the enzymes DHFRIIa, IIb and IIc, respectively.9,10 These enzymes have significantly shorter amino acid sequences (78 residues) when compared with the type A DHFR proteins (Table
).
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Thorough searches of sequence databases can be useful to avoid duplicating cassette names. However, it is clear in light of the rapid growth in the number of gene cassettes that a centralized system is required, where sequences are submitted for assignment of cassette numbers before publication of the corresponding paper.
Notes
J Antimicrob Chemother 2001; 47: 495–496
* Corresponding author. Tel: +61-2-9382-9096; Fax: +61-2-9398-4275; E-mail: whitepa{at}sesahs.nsw.gov.au 
References
1 . Hall, R. M. & Collis, C. M. (1998). Antibiotic resistance in gram-negative bacteria—the role of gene cassettes and integrons. Drug Resistance Updates 1, 109–19.
2
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Chang, C. Y., Chang, L. L., Chang, Y. H., Lee, T. M., Li, Y. H. & Chang, S. F. (2000). Two new gene cassettes, drf17 (for trimethoprim resistance) and aadA4 (for spectinomycin/streptomycin resistance), inserted in an Escherichia coli class 1 integron. Journal of Antimicrobial Chemotherapy 46, 87–9.
3 . White, P. A., McIver, C. J., Deng, Y. & Rawlinson, W. D. (2000). Characterisation of two new gene cassettes, aadA5 and dfrA17. FEMS Microbiology Letters 182, 265–9.[ISI][Medline]
4
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Sandvang, D. (1999). Novel streptomycin and spectinomycin resistance gene as a gene cassette within a class 1 integron isolated from Escherichia coli. Antimicrobial Agents and Chemotherapy 43, 3036–8.
5
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Adrian, P. V., Thomson, C. J., Klugman, K. P. & Amyes, S. G. B. (2000). New gene cassettes for trimethoprim resistance, dfr13, and streptomycin–spectinomycin resistance, aadA4, inserted on a class 1 integron. Antimicrobial Agents and Chemotherapy 44, 355–61.
6 . Naas, T., Poirel, L. & Nordmann, P. (1999). Molecular characterisation of In51, a class 1 integron containing a novel aminoglycoside adenylyltransferase gene cassette, aadA6, in Pseudomonas aeruginosa. Biochimica et Biophysica Acta 1489, 445–51.[Medline]
7
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Mazel, D., Dychinco, B., Webb, V. A. & Davies, J. (2000). Antibiotic resistance in the ECOR collection: integrons and identification of a novel aad gene. Antimicrobial Agents and Chemotherapy 44, 1568–74.
8 . Recchia, G. D. & Hall, R. M. (1995). Gene cassettes—a new class of mobile element. Microbiology 141, 3015–27.[ISI][Medline]
9 . Swift, G., McCarthy, B. J. & Heffron, F. (1981). DNA sequence of a plasmid-encoded dihydrofolate reductase. Molecular and General Genetics 181, 441–7.
10
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Radstrom, P., Skold, O., Swedberg, G., Flensburg, J., Roy, P. H. & Sundstrom, L. (1994). Transposon Tn5090 of plasmid R751, which carries an integron, is related to Tn7, Mu, and the retroelements. Journal of Bacteriology 176, 3257–68.
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