OqxAB, a Quinolone and Olaquindox Efflux Pump, Is Widely Distributed among Multidrug-Resistant Klebsiella pneumoniae Isolates of Human Origin

Pérez, Federico; Rudin, Susan D.; Marshall, Steven H.; Coakley, Peter; Chen, Liang; Kreiswirth, Barry N; Rather, Philip N.; Hujer, Andrea M.; Toltzis, Philip; Duin, David van; Paterson, David L.; Bonomo, Robert A.

doi:10.1128/aac.00725-13

Cited by 61 publications

(41 citation statements)

References 10 publications

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“…Linkage of oqxAB with genes for CTX-M-14 and other plasmid-mediated CTX-M alleles has been noted (160). It is common (usually 75% or more) on the chromosome of K. pneumoniae isolates, where up to 20-fold variation in expression implies the presence of regulatory control (73, 203, 206, 208, 209). In K. pneumoniae overexpression of the nearby rarA gene is associated with increased oqxAB expression, while increased expression of adjacent oqxR gene downregulates OqxAB production (210, 211).…”

Section: Qepa and Oqxabmentioning

confidence: 99%

Plasmid-Mediated Quinolone Resistance

2014

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Summary 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.

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Section: Qepa and Oqxabmentioning

confidence: 99%

Plasmid-Mediated Quinolone Resistance

2014

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“…Linkage of oqxAB with genes for CTX-M-14 and other plasmid-mediated CTX-M alleles has been noted (160). It is common (usually 75% or more) on the chromosome of K. pneumoniae isolates, where up to 20-fold variation in expression implies the presence of regulatory control (73,203,206,208,209). In K. pneumoniae overexpression of the nearby rarA gene is associated with increased oqxAB expression, while increased expression of adjacent oqxR gene downregulates OqxAB production (210,211).…”

Section: Qepa and Oqxabmentioning

confidence: 99%

Plasmid-Mediated Quinolone Resistance

Jacoby¹

2017

Antimicrobial Drug Resistance

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SummaryThree 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.

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“…Dependent on the host TolC protein, OqxAB has a wide substrate specificity, making E. coli also more resistant to fluoroquinolones, nalidixic acid, chloramphenicol, trimethoprim, benzalkonium chloride, and SDS (709). The oqxAB genes have since increasingly been found on R plasmids from E. coli (710)(711)(712)(713)(714) and several other species of Enterobacteriaceae, such as Salmonella and K. pneumoniae (235,236,303,715). The coexistence of the oqxAB and floR or CTX-M gene on the same plasmids was also observed (713,715).…”

Section: Drug Efflux Genes On Plasmidsmentioning

confidence: 99%

“…In addition to MDR mediated by the chromosomally encoded OqxAB pump (302)(303)(304), overexpression of the newly identified RND-type KpgABC pump was involved in tigecycline nonsusceptibility due to an IS element insertion in the promoter region of kpgABC (305). The KexD RND pump expressed by cloning provides MDR with the requirement of AcrA accessory and KocC OM proteins (306).…”

Section: Klebsiella Pneumoniaementioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

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OqxAB, a Quinolone and Olaquindox Efflux Pump, Is Widely Distributed among Multidrug-Resistant Klebsiella pneumoniae Isolates of Human Origin

Cited by 61 publications

References 10 publications

Plasmid-Mediated Quinolone Resistance

Plasmid-Mediated Quinolone Resistance

Plasmid-Mediated Quinolone Resistance

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

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