Abstract
qnrD is a plasmid mediated quinolone resistance gene from unknown origin, recently described in Enterobacteriaceae. It encodes a pentapeptide repeat protein 36–60% different from the other Qnr (A, B, C, S and VC). Since most qnrD-positive strains were described as strains belonging to Proteus or Providencia genera, we hypothesized that qnrD originated in Proteeae before disseminating to other enterobacterial species. We screened 317 strains of Proteeae for qnrD and its genetic support by PCR. For all the seven qnrD-positive strains (4 Proteus mirabilis, 1 Proteus vulgaris and 2 Providencia rettgeri) the gene was carried onto a small non-transmissible plasmid, contrarily to other qnr genes that are usually carried onto large multi-resistant plasmids. Nucleotide sequences of the qnrD-bearing plasmids were 96% identical. Plasmids contained 3 ORFs apart from qnrD and belonged to an undescribed incompatibility group. Only one plasmid, in P. vulgaris, was slightly different with a 1,568-bp insertion between qnrD and its promoter, leading to absence of quinolone resistance. We sought for similar plasmids in 15 reference strains of Proteeae, but which were tested negative for qnrD, and found a 48% identical plasmid (pVERM) in Providencia vermicola. In order to explain how qnrD could have been inserted into such native plasmid, we sought for gene mobilization structures. qnrD was found to be located within a mobile insertion cassette (mic) element which sequences are similar to one mic also found in pVERM. Our conclusions are that (i) the small non-transmissible qnrD-plasmids described here may result from the recombination between an as-yet-unknown progenitor of qnrD and pVERM, (ii) these plasmids are maintained in Proteeae being a qnrD reservoir (iii) the mic element may explain qnrD mobilization from non-transmissible plasmids to mobilizable or conjugative plasmids from other Enterobacteriaceae, (iv) they can recombined with larger multiresistant plasmids conjugated in Proteeae.
Highlights
Quinolones inhibit replication and transcription by inhibiting the bacterial type II topoisomerases, DNA gyrase and topoisomerase IV [1]
Small Non-transmissible Plasmids are the Genetic Support of qnrD in Proteeae Isolates qnr gene screening of the 317 clinical isolates resulted in eight (2.6%) qnr-positive strains with seven strains (87.5% of qnr-positive isolates) carrying qnrD: four P. mirabilis (DPROT11, DPROT104, DPROT189, and DPROT304), two P. rettgeri (DIJ09-518 and GHS09-09) and one P. vulgaris (DPROT78)
On the basis of epidemiological findings (Table 2) and Random Amplification of Polymorphic DNA (RAPD) profiles, the isolates belonging to the same species (4 P. mirabilis, 2 P. rettgeri) were distinct strains
Summary
Quinolones inhibit replication and transcription by inhibiting the bacterial type II topoisomerases, DNA gyrase and topoisomerase IV [1]. Fluoroquinolones (the main subgroup of quinolones) are currently among the most heavily prescribed antimicrobials in the world because of their pharmacodynamic and pharmacokinetic properties [1]. They are very potent, especially for treatment of urinary tract infections due to Enterobacteriaceae [1,2], and as a consequence of their intense use, quinolone resistance rate has increased much for the last years [1,3,4]. Clinical resistance mostly results from the combination of several mechanisms [1] Most of these mechanisms are chromosome-mediated [1,2] but plasmid-mediated genes have been described for a decade [5]. Most of these mechanisms are chromosome-mediated [1,2] but plasmid-mediated genes have been described for a decade [5]. qnr genes were the first plasmidmediated quinolone resistance genes described in 1998 [6]
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