Plasmid-Mediated Quinolone Resistance

Jacoby, George A.

doi:10.1007/978-1-59745-180-2_17

Cited by 12 publications

(18 citation statements)

References 72 publications

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“…Of the three altered positions in ParC, one has been linked to resistance in E. coli (position 80 [E. coli numbering]), while the substitution in ParE was outside the QRDR. Additionally, the Indian strain did not contain any known or putative mobile quinolone resistance genes (qnr genes) (41,54). The mutations present in the quinolone target genes are thus a likely explanation for the considerable increase in MICs of all tested quinolones.…”

Section: Discussionmentioning

confidence: 99%

Acquired Genetic Mechanisms of a Multiresistant Bacterium Isolated from a Treatment Plant Receiving Wastewater from Antibiotic Production

Johnning

Moore

Svensson-Stadler

et al. 2013

Appl Environ Microbiol

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The external environment, particularly wastewater treatment plants (WWTPs), where environmental bacteria meet human commensals and pathogens in large numbers, has been highlighted as a potential breeding ground for antibiotic resistance. We have isolated the extensively drug-resistant Ochrobactrum intermedium CCUG 57381 from an Indian WWTP receiving industrial wastewater from pharmaceutical production contaminated with high levels of quinolones. Antibiotic susceptibility testing against 47 antibiotics showed that the strain was 4 to >500 times more resistant to sulfonamides, quinolones, tetracyclines, macrolides, and the aminoglycoside streptomycin than the type strain O. intermedium LMG 3301 T . Whole-genome sequencing identified mutations in the Indian strain causing amino acid substitutions in the target enzymes of quinolones. We also characterized three acquired regions containing resistance genes to sulfonamides (sul1), tetracyclines [tet(G) and tetR], and chloramphenicol/ florfenicol (floR). Furthermore, the Indian strain harbored acquired mechanisms for horizontal gene transfer, including a type I mating pair-forming system (MPF I ), a MOB P relaxase, and insertion sequence transposons. Our results highlight that WWTPs serving antibiotic manufacturing may provide nearly ideal conditions for the recruitment of resistance genes into human commensal and pathogenic bacteria.

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Section: Discussionmentioning

confidence: 99%

Acquired Genetic Mechanisms of a Multiresistant Bacterium Isolated from a Treatment Plant Receiving Wastewater from Antibiotic Production

Johnning

Moore

Svensson-Stadler

et al. 2013

Appl Environ Microbiol

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“…In contrast, plasmid-mediated low-level resistance mechanisms may also compromise the efficacy of quinolones (13). The first report ofplasmid-mediated quinolone resistance described the presence of a 218-amino-acid protein termed Qnr that protects DNA from quinolone binding to topoisomerases (14).…”

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confidence: 99%

Plasmidic qnr Genes Confer Clinical Resistance to Ciprofloxacin under Urinary Tract Physiological Conditions

Martín-Gutiérrez

Rodríguez-Martínez

Pascual

et al. 2017

Antimicrob Agents Chemother

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Escherichia coli variants expressing plasmid-mediated qnr genes are usually susceptible to fluoroquinolones by standard susceptibility testing. Here we show that, under specific urinary tract physiological conditions, susceptible laboratory and clinical strains harboring qnr determinants become fully resistant to ciprofloxacin (CIP). Therefore, physiological conditions, mainly urine pH values, should be considered when performing susceptibility testing of CIP activity against E. coli in treating urinary tract infection (UTI) and for selecting appropriate antibiotics for UTI treatment.KEYWORDS ciprofloxacin, Escherichia coli, MIC, pH, qnr, urinary tract infection F luoroquinolones (FQs) are broad-spectrum antibiotics commonly used for urinary tract infection (UTI) (1-3). However, in recent years, a worrisome increase in resistance to FQs has been addressed worldwide (4, 5). Bacterial resistance to FQs is achieved mainly through the acquisition of sequential mutations in genes encoding DNA gyrase and topoisomerase IV (6, 7). The presence of some of these highly prevalent mutations (8, 9) often confers a low-level quinolone resistance (LLQR) phenotype with an MIC lower than the clinical breakpoint but higher than the epidemiological cutoff (10, 11). Therefore, low-level quinolone-resistant Escherichia coli mutants have been traditionally considered to be susceptible according to standard susceptibility testing. However, we recently found that growth under physiological urinary tract conditions (i.e., growth in urine, at low pH values, and under anaerobiosis) conferred clinical levels of resistance to the fluoroquinolone ciprofloxacin (CIP) (12). This situation may provide a selective scenario for the evolution of high-level quinolone resistance and could lead to therapeutic failure in patients with urinary tract infection (UTI).In contrast, plasmid-mediated low-level resistance mechanisms may also compromise the efficacy of quinolones (13). The first report ofplasmid-mediated quinolone resistance described the presence of a 218-amino-acid protein termed Qnr that protects DNA from quinolone binding to topoisomerases (14). Since then, five groups of plasmidic Qnr determinants (encoded by the genes qnrA, qnrB, qnrC, qnrD, qnrS, and qnrVC) have been described (15). Due to their plasmidic nature, qnr genes can be horizontally transferred, which confers an LLQR phenotype (15,16). Furthermore, qnr genes are often associated with extended-spectrum ␤-lactamases and aminoglycosideresistance-encoding genes on the same plasmid (17), mutually increasing the probability of dissemination (18).

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“…Quinolone efflux pumps are also found on certain plasmids that mediate quinolone resistance [45,46,57]. Plasmid-mediated quinolone resistance has additional mechanisms that involve Qnr proteins that inhibit the formation of the topoisomerase-DNA-quinolone ternary complex, or an acetyltransferase that can covalently modify the structure of quinolones [5,45,46,57]. The plasmid-mediated mechanisms generally result in low-level resistance that may lead to development of high-level resistance subsequently.…”

Section: Mechanisms Of Resistance and Potential Counteractionsmentioning

confidence: 99%

“…The altered efflux regulation can result in resistance to a whole spectrum of antibiotics, and efflux pump inhibitors are an active area of investigation in the research efforts to overcome antibiotic resistance [53][54][55][56]. Quinolone efflux pumps are also found on certain plasmids that mediate quinolone resistance [45,46,57]. Plasmid-mediated quinolone resistance has additional mechanisms that involve Qnr proteins that inhibit the formation of the topoisomerase-DNA-quinolone ternary complex, or an acetyltransferase that can covalently modify the structure of quinolones [5,45,46,57].…”

Section: Mechanisms Of Resistance and Potential Counteractionsmentioning

confidence: 99%

Targeting Bacterial Topoisomerases: How to Counter Mechanisms of Resistance

Tse‐Dinh

2016

Future Med. Chem.

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DNA gyrase and topoisomerase IV are type IIA bacterial topoisomerases that are targeted by highly effective antibiotics. However, resistance via multiple mechanisms arises to limit the efficacies of these drugs. Continued research on type IIA bacterial topoisomerases has provided novel approaches to counter the most common resistance mechanism for utilization of these proven targets in antibacterial therapy. Bacterial topoisomerase I is being explored as an alternative target that is not expected to show cross-resistance. Dual targeting or combination therapy could be strategies for circumventing the development of resistance to topoisomerase-targeting antibiotics. Bacterial topoisomerases are high-value bactericidal targets that could continue to be exploited for antibacterial therapy, if new tactics to counter resistance can be adopted.

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Plasmid-Mediated Quinolone Resistance

Cited by 12 publications

References 72 publications

Acquired Genetic Mechanisms of a Multiresistant Bacterium Isolated from a Treatment Plant Receiving Wastewater from Antibiotic Production

Acquired Genetic Mechanisms of a Multiresistant Bacterium Isolated from a Treatment Plant Receiving Wastewater from Antibiotic Production

Plasmidic qnr Genes Confer Clinical Resistance to Ciprofloxacin under Urinary Tract Physiological Conditions

Targeting Bacterial Topoisomerases: How to Counter Mechanisms of Resistance

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