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. 2003 Dec;47(12):3998–3999. doi: 10.1128/AAC.47.12.3998-3999.2003

Unambiguous Numbering of Antibiotic Resistance Genes

Ruth Hall 1,2,*, Sally Partridge 1,2
PMCID: PMC296178  PMID: 14638521

In the past, key individuals and networks of researchers interested in resistance to particular antibiotics kept track of numbering of genes, but this system is no longer always effective. With the pace of discovery of new resistance genes increasing, it is becoming more common for the same distinguishing number to be used for two different resistance genes that are reported at the same time or close together. For example, in the last few years, this has occurred twice with the dfrA-type trimethoprim resistance genes; it has also occurred with the aacA-type aminoglycoside resistance genes and the aadA-type streptomycin and spectinomycin resistance genes. Furthermore, even after assignments have been sorted out subsequently, database entries have not always been corrected, and the confusion is perpetuated in the literature.

A simple solution to this problem is for genes to be assigned numbers in order of the release of relevant sequences into the public domain as entries in the GenBank/EMBL databases. As these databases are accessible to all, thorough searches by authors prior to publication can be used to ensure orderly numbering and prevent duplication of gene assignments. Authors can then assume responsibility for appropriate numbering of a novel gene by releasing their sequences prior to publication, at the proof stage at the latest, and conducting appropriate searches again at that time.

We propose that the release of database entries indicating the correct gene number prior to publication, either at acceptance or proof stage, should become a prerequisite for publication of new resistance gene sequences. A future goal might be to establish a resistance gene database that is readily accessible and interactive.

Antimicrob Agents Chemother. 2003 Dec;47(12):3998–3999.

Editors' Reply

Patricia A Bradford 1,2,3,4,5,*, Karen Bush 1,2,3,4,5, George A Jacoby 1,2,3,4,5, Louis B Rice 1,2,3,4,5, Lowell S Young 1,2,3,4,5

Drs. Hall and Partridge draw our attention to an important problem regarding the naming and numbering of genes involved in antibiotic resistance. With the advent of rapid sequencing, there has been an explosion of newly characterized antibiotic resistance genes of many types. Some of these differ by a single nucleotide change, resulting in a single amino acid change that may or may not change the phenotype of the resultant protein.

Nomenclature for various resistance genes has been proposed for β-lactam (1), tetracycline (2), and macrolide-lincosamide-streptogramin B (3) resistance determinants. In the β-lactamase arena, the problem of duplicate names andnumbers was addressed in the mid-1990s. A β-lactamase website has been established whereby all sequences, literature references, or database accession numbers for most β-lactamase families are posted and numbers are assigned (http://www.lahey.org/studies/webt.htm) by Karen Bush and George Jacoby as the keepers of the website. Individual researchers may choose not to have the sequences posted until they are published; however, the sequences must be disclosed to the keepers. Before this process was initiated, an ad hoc meeting of all interested β-lactamase researchers was held during the Interscience Conference on Antimicrobial Agents and Chemotherapy in 1996. At the meeting, it was agreed that β-lactamase genes published in American Society for Microbiology journals must go through this process, and most researchers are now adhering to this process. This system appears to be working well for the β-lactamase world, but it is dependent upon the cooperation of each researcher and the voluntary participation by the two keepers of the website.

While most researchers readily deposit the sequences of newly characterized antibiotic resistance genes in GenBank (http://www.ncbi.nlm.nih.gov/GenBank/index.html), there are several problems. First, GenBank does not require that a deposited sequence be unique. Therefore, several duplicate sequences for any given gene may be present. Second, many researchers ask that their sequences not be disclosed until the time of publication. By doing this, they have a claim on the gene with a certain deposit date, but it cannot be viewed by anyone doing a search. If a second researcher also obtains an identical sequence, there is no way to know that someone else has also claimed the sequence and/or name. If these genes are submitted for publication in different journals, duplication may appear in the literature, requiring renumbering through a consensus in later publications.

Drs. Hall and Partridge have suggested that the sequences encoding new antibiotic resistance genes deposited in GenBank be disclosed prior to publication. These suggestions might avoid some of the mishaps that have taken place in the literature regarding double naming of antibiotic resistance genes, but certainly not all. While this is a valid suggestion, it would require that we as editors trust the authors or our reviewers to do thorough searches of the databases at the time of submission, when the manuscript goes back after modification, and when the page proofs are received. Perhaps what is needed is a central clearing house with bioinformatics capabilities to serve as a repository for all sequences and name designations for genes encoding antibiotic resistance. The editors welcome volunteers to serve as curators of such a site.

REFERENCES

  • 1.Bush, K., and G. A. Jacoby. 1997. Nomenclature of TEM β-lactamases. J. Antimicrob. Chemother. 39:1-3. [DOI] [PubMed] [Google Scholar]
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Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

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