Osong Public Health and Research Perspectives

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Resistance to Fluoroquinolone by a Combination of Efflux and Target Site Mutations in Enteroaggregative Escherichia coli Isolated in Korea: Jun-Young Kim, Se-Mi Jeon, Hyungjun Kim, Nara Lim, Mi-Sun Park, Seong-Han Kim; Osong Public Health Res Perspect. 2012;3(4):239-244. Published online December 31, 2012; DOI: https://doi.org/10.1016/j.phrp.2012.11.002

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Objectives
Enteroaggregative Escherichia coli (EAEC) was recently reported as a major diarrheagenic pathogen in infant and adult travelers, both in developing and developed countries. EAEC strains are known to be highly resistant to antibiotics including quinolones. Therefore in this study we have determined the various mechanisms of quinolone resistance in EAEC strains isolated in Korea.
Methods
For 26 EAEC strains highly resistant to fluoroquinolone, minimal inhibitory concentrations for fluoroquinolones were determined, mutations in the quinolone target genes were identified by PCR and sequencing, the presence of transferable quinolone resistance mechanism were identified by PCR, and the contribution of the efflux pump was determined by synergy tests using a proton pump inhibitor. The expression levels of efflux pump-related genes were identified by relative quantification using real-time PCR.
Results
Apart from two, all tested isolates had common mutations on GyrA (Ser83Leu and Ser87Gly) and ParC (Ser80Gln). Isolates EACR24 and EACR39 had mutations that have not been reported previously: Ala81Pro in ParC and Arg157Gly in GyrA, respectively. Increased susceptibility of all the tested isolates to ciprofloxacin and norfloxacin in the presence of the pump inhibitor implies that efflux pumps contributed to the resistance against fluoroquinolones. Expression of the efflux pump-related genes, tolC, mdfA, and ydhE, were induced in isolates EACR 07, EACR 29, and EACR 33 in the presence of ciprofloxacin.
Conclusion
These results indicate that quinolone resistance of EAEC strains mainly results from the combination of mutations in the target enzyme and an increased expression of efflux pump-related genes. The mutations Ala81Pro in ParC and Arg157Gly in GyrA have not been reported previously the exact influence of these mutations should be investigated further.

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Detection of gyrA and parC Mutations and Prevalence of Plasmid-Mediated Quinolone Resistance Genes in Klebsiella pneumoniae
Sawsan Mohammed Kareem, Israa MS Al-kadmy, Saba S Kazaal, Alaa N Mohammed Ali, Sarah Naji Aziz, Rabab R Makharita, Abdelazeem M Algammal, Salim Al-Rejaie, Tapan Behl, Gaber El-Saber Batiha, Mohamed A El-Mokhtar, Helal F Hetta
Infection and Drug Resistance.2021; Volume 14: 555. CrossRef
Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance
Mariana Ferreira, Paula Gameiro
Microorganisms.2021; 9(7): 1506. CrossRef
Frequency of DNA gyrase and topoisomerase IV mutations and plasmid-mediated quinolone resistance genes among Escherichia coli and Klebsiella pneumoniae isolated from urinary tract infections in Azerbaijan, Iran
Robab Azargun, Mohammad Hossein Soroush Barhaghi, Hossein Samadi Kafil, Mahin Ahangar Oskouee, Vahid Sadeghi, Mohammad Yousef Memar, Reza Ghotaslou
Journal of Global Antimicrobial Resistance.2019; 17: 39. CrossRef
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Kassandra L. Grimes, Laura J. Dunphy, Erica M. Loudermilk, A. Jasmin Melara, Glynis L. Kolling, Jason A. Papin, Lisa M. Colosi
Chemosphere.2019; 237: 124421. CrossRef
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Yuehua Gong, Yuan Yuan
Critical Reviews in Microbiology.2018; 44(3): 371. CrossRef
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Shivangi Sachdeva, Raghuvamsi V. Palur, Karpagam U. Sudhakar, Thenmalarchelvi Rathinavelan
Frontiers in Microbiology.2017;[Epub] CrossRef
Plasmid-Mediated Quinolone Resistance in Different Diarrheagenic Escherichia coli Pathotypes Responsible for Complicated, Noncomplicated, and Traveler's Diarrhea Cases
Silvia Herrera-León, María Teresa Llorente, Sergio Sánchez
Antimicrobial Agents and Chemotherapy.2016; 60(3): 1950. CrossRef
Determinants of quinolone resistance in Escherichia coli causing community-acquired urinary tract infection in Bejaia, Algeria
Yanat Betitra, Vinuesa Teresa, Viñas Miguel, Touati Abdelaziz
Asian Pacific Journal of Tropical Medicine.2014; 7(6): 462. CrossRef

A Contribution of MdfA to Resistance to Fluoroquinolones in Shigella flexneri: Jun-Young Kim, Se-Mi Jeon, Hyungjun Kim, Mi-Sun Park, Seong-Han Kim; Osong Public Health Res Perspect. 2011;2(3):216-217. Published online December 31, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.11.049

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Abstract PDF

In this study, we measured the drug resistance conferred by mdfA mutations in two Shigella flexneri strains. A mutant in mdfA genes was constructed by polymerase chain reaction–based, one-step inactivation of chromosomal genes. The antimicrobial susceptibility of parent and mutant strains to fluoroquinolones was determined by minimal inhibitory concentration (MICs). The △mdfA mutants were somewhat more susceptible to fluoroquinolones than the parent strains. The low level changes in MICs of the △mdfA mutants suggest that mdfA contributed the fluoroquinolone resistance in S flexneri. This finding found that the increased expression level of an MdfA efflux pump mediated fluoroquinolone resistance, but it is not likely a major effecter of higher resistance levels.

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Alterations of gyrA, gyrB, and parC and Activity of Efflux Pump in Fluoroquinolone-resistant Acinetobacter baumannii: Sunok Park, Kyeong Min Lee, Yong Sun Yoo, Jung Sik Yoo, Jae Il Yoo, Hwa Su Kim, Yeong Seon Lee, Gyung Tae Chung; Osong Public Health Res Perspect. 2011;2(3):164-170. Published online December 31, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.11.040

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Abstract PDF

Objectives
This study investigated the fluoroquinolone-resistant mechanism of 56 clinical cases of A baumannii infection from 23 non-tertiary hospitals, collected between 2004 and 2006.
Methods
Susceptibility testing was performed by broth microdilution and Epsilometer test. Analyses of quinolone resistance-determining region (QRDR) were done by sequencing. The activity of the efflux pump was measured using inhibitors.
Results
The sequences from selected 56 isolates were divided into seven groups (I-VII) on the basis of mutations in gyrA (S83L), parC (S80L, S80W and S84K) and gyrB (containing the novel mutations E679D, D644Y and A677V). The 27 isolates with triple mutations in gyrA, gyrB and parC (groups IV-VII) showed higher levels of resistance to ciprofloxacin (minimal inhibitory concentration [MIC] of 16-256 μg/mL) than the 26 isolates with double mutations in gyrA and parC (groups II and III, MIC of 8-64 μ g/mL; p < 0.05). Alterations in the efflux pump were observed in four isolates with the parC S80L mutation (group II) or E84K mutation (group VII), but no effect was observed in an isolate with the parC S80 W mutation (group III).
Conclusion
These results suggest that triple mutations in clinical isolates of A baumannii contribute to the development of high levels of resistance to fluoroquinolones and that mutations in parC S80L or E84K (groups II and VII) may contribute to alterations in efflux pump activity in A baumannii.

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