Investigation of plasmid-mediated quinolone resistance genes in carbapenem resistant Enterobacterales

Abstract

Fluoroquinolones, are effective agents both against gram-positive and gram-negative bacteria. Quinolones show bactericidal effect as a result of inhibition of DNA gyrase and topoisomerase IV enzymes. Main quinolo resistance mechanisms are chromosomal mutations in these enzymes and decreased intracellular accumulation due to efflux pumps or decreased membrane uptake. Recently a new quinolone resistance mechanism mediated by plasmids has been defined. These plasmids carry genes called as qnr. Qnr genes do not cause quinolone resistance but they cause decreased quinolone susceptibility and lead to higher minimum inhibitory concentrations. Currently there are qnrA, qnrB, qnrC, qnrD and qnrS genes. This study was aimed to investigate the presence of plasmid-mediated quinolone resistance determinants in carbapenem resistant Enterobacterales isolates. A total 154 carbapenem resistant Enterobacterales isolates were included in the study. Presence of qnrA, qnrB, qnrC, qnrD and qnrS genes were investigated by multiplex polymerase chain reaction (PCR) method. The results of the PCR amplification revealed that qnrA was detected in two isolates (E6, E85) (1.29%), qnrB was detected in 12 isolates (8.4%) (E32, E43, E46, E61, E62, E84, E94, E149, E 166, E167, E177, E179) and qnrS was detected in six isolates (E15, E25, E57, E63, E70, E80) (4.54%). And one isolate (E9) was both positive for qnrB and qnrS. QnrC and qnrD were not detected in any isolates. Transferable quinolone resistance due to the dissemination of qnr genes may have important impacts in terms of infection control and treatment problems. Survey of plasmid mediated quinolone resistance will help to determine the size of the issue and guide the measures that should be taken to avoid escalation of resistance and dissemination problem.

Keywords

• qnr
• Enterobacterales,
• quinolone

References

1. 1-Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis. 2011; 17: 1791.
2. 2-Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis. 2009; 9: 228-36.
3. 3-Appelbaum PC, Hunter PA. The fluoroquinolone antibacterials: past, present and future perspectives. Int J Antimic Agents. 2000; 16: 5-15.
4. 4- Hooper D. Quinolones. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Churchill Livingstone: Elsevier; 2005: 451-70.
5. 5- Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria. Drugs. 2004; 64: 159-204.
6. 6- Cattoir V, Nordmann P. Plasmid-mediated qunolone resistance in gram negative bacterial species: An update. Curr Med Chem. 2009; 51: 1109-17.
7. 7- Martinez- Martinez L, Pascual A, Jacoby GA. Quinolone resistance from a transferable plasmid. Lancet. 1998; 14: 797-9.
8. 8- Strahilevitz J, Jacoby GA, Hooper D, Robiscek A. Plasmid-mediated quinolone resistance: a multifaceted threat. Clin Microb Rev. 2009; 22: 664-89.

9. 9- Poirel L, Cattoir V, Nordmann P. Is plasmid-mediated quinolone resistance a clinically significant problem? Clin Microbiol Infect. 2008; 14:295-7.
10. 10- Kim HB, Park CH, Kim CJ, Kim EC, Jacoby GA, Hooper DC. Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year period. Antimicrob Agents Chemother. 2009; 53: 639-45.
11. 11- Cavaco LM, Hasman H, Xia S, Aarestrup FM. qnrD, a Novel Gene Conferring Transferable Quinolone Resistance in Salmonella enterica Serovar Kentucky and Bovismorbificans Strains of Human Origin. Antimicrob Agents Chemother. 2009; 53:603-8.
12. 12- Hooper D. Mechanisms of action and resistance of older and newer fluoroquinolones. Clin Infect Dis. 2000; 3124-8.
13. 13- Jacoby GA. Mechanisms of resistance to quinolones. Clin Infect Dis. 2005; 41:120–6.
14. 14- Poirel L, Cattoir V, Nordmann P. Plasmid mediated quinolone resistance; interactions between human, animal, and environmental ecologies. Front Microbiol. 2012; 3(24):1–7.
15. 15- https://www.lahey.org/lhmc/research-residencies/research/clinical-research/
16. 16- Nazik H, Ongen B, Kuvat N. Investigation of plasmid-mediated quinolone resistance among isolates obtained in a Turkish intensive care unit. Jpn J Infect Dis. 2008; 61: 310–2.
17. 17- Öktem IMA, Gulay Z, Bicmen M, Gur D, HITIT Project study Group. Qnr A prevalence in extended-spectrum beta-lactamase positive Enterobacteriaceae isolates from Turkey. Jpn J Infect Dis. 2008; 61: 13-7.
18. 18- Poirel L, Gur Di Minarini L, Arslan U, Nordmann P. Molecular epidemiology of plasmid-mediated quinolone resistance determinants in extended-spectrum beta-lactamase producing E. coli and K. pneumoniae isolates from Turkey, 18th European Congressof Clinical Microbiology and ınfectious Diseases. P1527: Barcelona; 2008.
19. 19-Çoban AY, Nohut OK, Tanrıverdi Çaycı Y, Bayramoğlu G, Pirinççiler M, Çetinkaya E et al. Investigation of plasmid-mediated quinolone resistance determinants in Enterobacteriaceae: a multicenter study. Mikrobiyol Bul. 2012; 46: 366-74.
20. 20- Herrera-Leon S, Gonzalez-Sanz R, Herrera-Leon L, Echita MA. Characterization of multidrug-resistant Enterobactericeae carrying plasmid-mediated quinolone resistance mechanisms in Spain. J Antimicrob Chemother. 2010; 66: 287-90.
21. 21- Veldman K, van Pelt W, Mevius D. First report of qnr genes in Salmonella in The Netherlands. J Antimicrob Chemother. 2008; 61: 452–3.
22. 22- Majlesi A, Kamali Kakhki R, Nejad AS, Yousefi Mashouf R, Roointan A, Abazari M et al. Detection of plasmid-mediated quinolone resistance in clinical isolates of Enterobacteriaceae strains in Hamadan, West of Iran. Saudi J Bio Sci. 2018; 25: 426–30.
23. 23- Djimabi Salah, Soubeiga ST, Ouattara AK, Sadji AY, Metuor-Dabire A, Obiri-Yeboah D et al. Distribution of quinolone resistance gene (qnr) in ESBL-producing Escherichia coli and Klebsiella spp. in Lomé, Togo. Antimicrob Res Infect Cont. 2019:1-8.
24. 24- Amin M, Dibachi S, Shahin M. Prevalence of class 1 integrons and plasmid-mediated qnr-genes among Enterobacter isolates obtained from hospitalized patients in Ahvaz, Iran. Le Infezioni in Medicina. 2017; 4: 351-7.