Mutations of gyrA and parC Genes in Ciprofloxacin-Resistance Isolates of Pseudomonas Aeruginosa from Burn Wounds in Yazd City, Iran

Document Type : Original Article (s)


1 Department of Medical Microbiology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Instructor, Department of Medical Microbiology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Associate Professor, Department of Community Medicine, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Assistant Professor, Department of Medical Microbiology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran


Background: Pseudomonas aeruginosa is one of the most important factors for nosocomial infections with percentage of resistance to the drug, particularly in the burn wounds. One of the mechanisms of resistance in these bacteria is chromosomal mutation in the quinolone-resistance-determining region (QRDR) of chromosome gene. The aim of this study was to evaluate gyrA and parC gene mutation in Pseudomonas aeruginosa isolates from burn wound infections resistant to ciprofloxacin.Methods: 50 clinical Pseudomonas aeruginosa isolates were identified from patients admitted to burn hospital. Minimum inhibitory concentrations (MICs) of ciprofloxacin were evaluated by E-test method and polymerase chain reaction-sequencing (PCR-sequencing) method was carried out to assess the gyrA and parC mutations in ciprofloxacin-resistant isolates.Findings: From 50 isolates, 62% were resistant to ciprofloxacin. Mutations were detected in all (100%) and 41 isolates (82%) in gyrA and parC genes, respectively. The most frequent mutations were observed in gyrA gene conversion (T83I) and parC (S87L). No mutation was found in sensitive isolates.Conclusion: Results indicate that mutations in the quinolone-resistance-determining-region are the major mechanisms for ciprofloxacin resistance in clinical isolates of Pseudomonas aeruginosa. Considering the prevalence of these genes, these mutations play a major role in the development of resistance.


  1. Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev 2009; 22(4): 582-610.
  2. Adams DE, Shekhtman EM, Zechiedrich EL, Schmid MB, Cozzarelli NR. The role of topoisomerase IV in partitioning bacterial replicons and the structure of catenated intermediates in DNA replication. Cell 1992; 71(2): 277-88.
  3. Zechiedrich EL, Khodursky AB, Cozzarelli NR. Topoisomerase IV, not gyrase, decatenates products of site-specific recombination in Escherichia coli. Genes Dev 1997; 11(19): 2580-92.
  4. Andersson MI, MacGowan AP. Development of the quinolones. J Antimicrob Chemother 2003; 51(Suppl 1): 1-11.
  5. Bayat E, Kamali M, Zareei Mahmoodabadi A, Mortazavi Y, Ebrahim Habibi A, Amini B, et al. Isolation, determination and cloning of translocation domain of exotoxin A from Pseudomonas aeruginosa. Trauma Mon 2010; 15(3): 149-154.
  6. Wolf P, Elsasser-Beile U. Pseudomonas exotoxin A: from virulence factor to anti-cancer agent. Int J Med Microbiol 2009; 299(3): 161-76.
  7. Michael B, Richard P. Organization for infection control. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010. p. 3669-76.
  8. Clinical and Laboratory Standards Institute (CLSI). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: Approved standard. CLSI document M07-A10. 10th ed. Wayne, PA: CLSI; 2015. p. 950.
  9. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3): 1215.
  10. Akasaka T, Tanaka M, Yamaguchi A, Sato K. Type II topoisomerase mutations in fluoroquinolone-resistant clinical strains of Pseudomonas aeruginosa isolated in 1998 and 1999: role of target enzyme in mechanism of fluoroquinolone resistance. Antimicrob Agents Chemother 2001; 45(8): 2263-8.
  11. Arvanitidou M, Katikaridou E, Douboyas J, Tsakris A. Prognostic factors for nosocomial bacteraemia outcome: a prospective study in a Greek teaching hospital. J Hosp Infect 2005; 61(3): 219-24.
  12. Nouri R, Ahangarzadeh Rezaee M, Hasani A, Aghazadeh M, Asgharzadeh M, Ghojazadeh M. Effect of QRDR mutations on ciprofloxacin resistance in clinical isolates of Pseudomonas aeruginosa. J Ardabil Univ Med Sci. 2016; 16 (2): 116-23. [In Persian].
  13. Salma R, Dabboussi F, Kassaa I, Khudary R, Hamze M. gyrA and parC mutations in quinolone-resistant clinical isolates of Pseudomonas aeruginosa from Nini Hospital in north Lebanon. J Infect Chemother 2013; 19(1): 77-81.
  14. Adabi M, Talebi Taher M, Arbabi L, Afshar M, Fathizadeh S, Minaeian S, et al. Determination of antibiotic resistance pattern of Pseudomonas aeruginosa strains isolated from patients with burn wounds. J Ardabil Univ Med Sci. 2015; 15(1): 66-74. [In Persian].
  15. Lee JK, Lee YS, Park YK, Kim BS. Alterations in the GyrA and GyrB subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa. Int J Antimicrob Agents 2005; 25(4): 290-5.
  16. Akasaka T, Onodera Y, Tanaka M, Sato K. Cloning, expression, and enzymatic characterization of Pseudomonas aeruginosa topoisomerase IV. Antimicrob Agents Chemother 1999; 43(3): 530-6.
  17. Pasca MR, Dalla VC, De Jesus Lopes Ribeiro AL, Buroni S, Papaleo MC, Bazzini S, et al. Evaluation of fluoroquinolone resistance mechanisms in Pseudomonas aeruginosa multidrug resistance clinical isolates. Microb Drug Resist 2012; 18(1): 23-32.
  18. Wang YT, Lee MF, Peng CF. Mutations in the quinolone resistance-determining regions associated with ciprofloxacin resistance in Pseudomonas aeruginosa isolates from Southern Taiwan. Biomarkers and Genomic Medicine 2014; 6(2): 79-83.
  19. Fazeli H, Solgi H, Havaei S A, Shokri D, Norouzi Barogh M, Zamani F Z. Carbapenem and fluoroquinolone resistance in multidrug resistant Pseudomonas aeruginosa Isolates from Al-Zahra Hospital, Isfahan, Iran. J Med Microbiol Infec Dis 2014; 2(4): 147-152.
  20. Kureishi A, Diver JM, Beckthold B, Schollaardt T, Bryan LE. Cloning and nucleotide sequence of Pseudomonas aeruginosa DNA gyrase gyrA gene from strain PAO1 and quinolone-resistant clinical isolates. Antimicrob Agents Chemother 1994; 38(9): 1944-52.
  21. Tohidpour A, Najar Peerayeh S, Najafi S. Detection of DNA gyrase mutation and multidrug efflux pumps hyperactivity in ciprofloxacin resistant clinical isolates of Pseudomonas aeruginosa. J Med Microbiol Infec Dis 2013; 1(1): 1-7.
  22. Gorgani N, Ahlbrand S, Patterson A, Pourmand N. Detection of point mutations associated with antibiotic resistance in Pseudomonas aeruginosa. Int J Antimicrob Agents 2009; 34(5): 414-8.