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Antimicrobial Agents and Chemotherapy, July 2008, p. 2297-2299, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00147-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

GUEST COMMENTARY

qnr Gene Nomenclature{triangledown}

George Jacoby,1* Vincent Cattoir,2 David Hooper,3 Luis Martínez-Martínez,4 Patrice Nordmann,2 Alvaro Pascual,5 Laurent Poirel,2 and Minggui Wang6

Lahey Clinic, Burlington, Massachusetts,1 INSERM U914, Hôpital de Bicêtre, Faculté de Médicine Paris-Sud, Université Paris XI, K.-Bicêtre, France,2 Massachusetts General Hospital, Boston, Massachusetts,3 Service of Microbiology, University Hospital Marqués de Valdecilla, Santander, Spain,4 Department of Microbiology, University of Seville-University Hospital Virgen Macarena, Seville, Spain,5 Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People's Republic of China6

Since the plasmid-borne quinolone resistance gene qnr was reported in 1998 (8), many additional qnr alleles have been discovered on plasmids or the bacterial chromosome (reviewed in references 9 and 13). The plasmid-borne qnr genes currently comprise three families, qnrA, qnrB, and qnrS, differing from each other 40% or more in nucleotide sequence. Within each family, minor (≤10%) variation in sequence has defined a growing number of alleles. For the qnrA and qnrS families, the number of variants has been manageable, with general agreement on allele designations, but lately, the number of qnrB sequences submitted to GenBank has exploded, with the same qnrB allele number claimed for dissimilar sequences by different investigators and the same entry given new allele numbers from week to week.

To bring order into the current qnrB numbering chaos, we propose numbering the qnr alleles according to the following rules: (i) priority should be given first to published numbers, then to those in accepted or submitted manuscripts, and finally to the date of submission to GenBank; (ii) only full-length sequences should be assigned allele numbers; (iii) naturally occurring alleles, not those created by mutation, will be numbered; (iv) only nucleotide alterations that result in amino acid changes and not functionally silent substitutions should be taken into account; (v) one or more amino acid alterations define a new allele; (vi) variation in promoter sequences is not considered; (vii) demonstration that an allele in an established family causes reduced susceptibility to nalidixic acid or a fluoroquinolone is desirable but is not required; (viii) a new family (such as qnrC) should differ substantially from existing families (≥30% difference suggested in nucleotides or derived amino acids) and should be shown to affect quinolone susceptibility; (ix) a database of qnr allele designations will be maintained at http://www.lahey.org/qnrStudies; and (x) further allele numbers will be assigned upon application.

Another source of confusion is the presence of two potential in-frame initiation codons for some qnrB alleles. For other qnrB alleles, the first ATG is out of phase with the second. The second ATG initiation codon, common to all, has been used here in numbering QnrB amino acids, and amino acid variations that would occur if the first initiation codon were used have been ignored. Consequently, QnrB proteins have 214 amino acids, whereas the QnrA and QnrS proteins are 218 amino acids in length.

qnr alleles in the GenBank database as of April 2008 were evaluated to identify unique sequences and then assigned allele numbers. Table 1 shows our proposed designations for qnrA, qnrB, and qnrS. No new full-length qnrA sequences were found, but a unique qnrS sequence was identified and designated qnrS3. Nineteen unique qnrB alleles were identified. GenBank listings for partial qnrB alleles (accession numbers EF421178, EF421180, EF571009, EF576718, EU127476, and EU325573) have been omitted. In addition, GenBank accession numbers EF634464 and EU093091 code for QnrB6, and accession number EU136182 encodes QnrB9. Accession number EU273765, expressed from the second potential start codon, is the same as QnrB13 in our listing. Tables 2, 3, and 4 show the amino acid alterations in particular variants. Although qnrB has the greatest number of sequence variants, amino acid differences are currently found at 27 of 214 possible sites (13%), a percentage less than the amino acid variability among TEM (20%) or SHV (27%) β-lactamases (http://www.lahey.org/Studies/).


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  		TABLE 1. Proposed Qnr allele designations


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  		TABLE 2. Amino acid substitutions in QnrA1 to QnrA6


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  		TABLE 3. Amino acid substitutions in QnrB1 to QnrB19a


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  		TABLE 4. Amino acid substitutions in QnrS1 to QnrS3

qnr genes have also been found on the chromosomes of both gram-positive (15) and gram-negative bacteria. We propose that they be termed qnr from a particular organism or, where a shorter designation is needed, given distinguishing initials such as Efsqnr from Enterococcus faecalis (1), Ppqnr from Photobacterium profundum (10), Vpqnr from Vibrio parahaemolyticus (16), or Vvqnr from Vibrio vulnificus (10). qnr letter designations, such as qnrA3 from Shewanella algae or SaqnrA3 should be used only if the gene is at least 70% identical to one of the established qnr families.

ACKNOWLEDGMENTS

This work was supported by grants AI43312 (to G.J.) and AI23988 (to D.H.) from the National Institutes of Health, U.S. Public Health Service; grant UPRES-EA3539 (to P.N.) from the Ministère de L'Education Nationale et de la Recherche; grant LSHM-CT-2005-018705from the European community (to P.N.); grants PI050690 (to L.M.-M.), PI060580 (to A.P.), and REIPI RD06/0008 (to A.P. and L.M.M.) from ISCIII, Ministerio de Sanidad y Consumo, Spain; grant 2005CB0523101 (to M.W.) from the National Basic Research Program of China; and grant 30572229 (to M.W.) from the National Natural Science Foundation of China.


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FOOTNOTES
 
* Corresponding author. Mailing address: Lahey Clinic, 41 Mall Road, Burlington, MA 01805. Phone: (781) 744-2928. Fax: (781) 744-5486. E-mail: george.a.jacoby{at}lahey.org Back

FOOTNOTES

{triangledown} Published ahead of print on 21 April 2008. Back

The views expressed in this Commentary do not necessarily reflect the views of the journal or of ASM.

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Antimicrobial Agents and Chemotherapy, July 2008, p. 2297-2299, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00147-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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