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Plasmid-mediated quinolone resistance.

ABSTRACT: Three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998. Plasmid genes qnrA, qnrB, qnrC, qnrD, qnrS, and qnrVC code for proteins of the pentapeptide repeat family that protects DNA gyrase and topoisomerase IV from quinolone inhibition. The qnr genes appear to have been acquired from chromosomal genes in aquatic bacteria, are usually associated with mobilizing or transposable elements on plasmids, and are often incorporated into sul1-type integrons. The second plasmid-mediated mechanism involves acetylation of quinolones with an appropriate amino nitrogen target by a variant of the common aminoglycoside acetyltransferase AAC(6')-Ib. The third mechanism is enhanced efflux produced by plasmid genes for pumps QepAB and OqxAB. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading. The plasmid-mediated mechanisms provide only low-level resistance that by itself does not exceed the clinical breakpoint for susceptibility but nonetheless facilitates selection of higher-level resistance and makes infection by pathogens containing PMQR harder to treat.

SUBMITTER: Jacoby GA

PROVIDER: S-EPMC4288778 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Plasmid-mediated quinolone resistance.

Jacoby George A GA Strahilevitz Jacob J Hooper David C DC

Microbiology spectrum 20141001 5

Three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998. Plasmid genes qnrA, qnrB, qnrC, qnrD, qnrS, and qnrVC code for proteins of the pentapeptide repeat family that protects DNA gyrase and topoisomerase IV from quinolone inhibition. The qnr genes appear to have been acquired from chromosomal genes in aquatic bacteria, are usually associated with mobilizing or transposable elements on plasmids, and are often incorporated into sul1-type integrons. The s ...[more]

PMID: 25584197

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Project description:A highly fluoroquinolone-resistant isolate of Aeromonas species was isolated from a wastewater treatment plant and found to possess multiple resistance mechanisms, including mutations in gyrA and parC, efflux pumps, and plasmid-mediated quinolone resistance (PMQR) genes. Complete sequencing of the IncU-type plasmid, pAC3, present in the strain revealed a circular plasmid DNA 15,872 bp long containing two PMQR genes [qnrS2 and aac(6')-Ib-cr]. A mobile insertion cassette element containing the qnrS2 gene and a typical miniature inverted-repeat transposable element (MITE) structure was identified in the plasmid. The present study revealed that this MITE sequence appears in other Aeromonas species plasmids and chromosomes. Plasmid pAC3 was introduced into Escherichia coli, and its PMQR genes were expressed, resulting in the acquisition of resistance. Proteome analysis of the recipient E. coli strain harboring the plasmid revealed that aac(6')-Ib-cr expression was constitutive and that qnrS2 expression was dependent upon fluoroquinolone stress through regulation by regulator of sigma D (Rsd). To the best of our knowledge, this is the first report to characterize a novel MITE sequence upstream of the PMQR gene within a mobile insertion cassette, as well as the regulation of qnrS2 expression. Our results suggest that this mobile element may play an important role in qnrS2 dissemination. IMPORTANCE In the present study, plasmid pAC3 isolated from a highly fluoroquinolone-resistant isolate of Aeromonas species was sequenced and found to contain two fluoroquinolone resistance genes, aac(6')-Ib-cr and qnrS2. Comparative analyses of plasmid pAC3 and other Aeromonas sp. IncU-type plasmids revealed a mobile insertion cassette element with a unique structure containing a qnrS2 gene and a typical miniature inverted-repeat transposable element (MITE) structure. This study also revealed that this MITE sequence appears in other Aeromonas species plasmids and chromosomes. Our results also demonstrate that the fluoroquinolone-dependent expression of qnrS2 is associated with rsd in E. coli DH5α harboring plasmid pAC3. Our findings suggest that the mobile element may play an important role in qnrS2 dissemination and that Aeromonas species constitute an important reservoir of fluoroquinolone resistance determinants in the environment.

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Plasmid-mediated quinolone resistance.

Publications

Plasmid-mediated quinolone resistance.

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