Evaluation of the Mutations in Topoisomerase IV Genes and Their Role in Development of Resistance to Quinolones in Streptococcus pneumonia
Abstract
Background: Streptococcus pneumoniae is an important cause of respiratory tract infections. Due to the recent incidence of antibiotic resistance to commonly used antibiotics, the use of quinolones in the treatment of S. pneumoniae has been taken into consideration. The aim of this study was to evaluate the molecular mechanisms of quinolone resistance in isolated strains.
Methods:This study was carried out on 45 strains of S. pneumoniae isolates from clinical samples. Initially, using biochemical tests, S. pneumoniae strains were determined and using lytA gene specific primers, these strains were accomplished. Antibiotic resistance was assessed by Clinical & Laboratory Standards Institute (CLSI) criteria and eventually, and then adopting Polymerase Chain Reaction- Restriction Fragment Length polymorphism (PCR-RFLP) techniques were studied with Sau3A andMspI enzymes. Also, point mutations associated with antibiotic resistance was evaluated in parC and parE genes.
Results: In 45 strains isolated, resistance to nalidixic acid, ciprofloxacin, ofloxacin, norfloxacin and levofloxacin was; 82.22%, 73.43%, 53.33%, 48.88%, and 42.22%, respectively. In clinical samples,34 (75.55%) strains with mutations in the parC genes and 14 (31.11%) strains with mutations in parE gene were detected. Using statistical analysis, it was found that there was a significant relationship between mutations in the parC genes and resistance to nalidixic acid, ciprofloxacin, norfloxacin and levofloxacin. However, mutations in parE genes only showed the significant correlation with resistance to norfloxacin exclusively. On the contrary, unlike other studies, we demonstrated that a mutation in the parE gene could be involved in low-level resistance to quinolones.
Conclusion: Due to the considerable resistance to quinolones, evaluation of these mutations isnecessary in other parts of the country.
2. Pan XS, Yague G, Fisher LM. Quinolone resistance mutations in Streptococcus pneumoniae GyrA and ParC proteins: mechanistic insights into quinolone action from enzymatic analysis, intracellular levels, and phenotypes of wild-type and mutant proteins. Antimicrob Agents Chemother 2001; 45:3140-7.
3. Balsalobre L, Ferrandiz MJ, Alba G, et al. Nonoptimal DNA Topoisomerases Allow Maintence of Supercoiling Level and Improve Fitness of Streptococcus pneumonia. Antimicrob Agent Chemother 2011; 55:1079-1105.
4. Patel S, Melano R, Mcgeer A, et al. Characterization of the Quinolone Resistant Determining Regions in Clinical Isolates of Pnumococci Collected in Canada. Ann Clin Microbiol Antimicrob 2010; 9:1-6.
5. Adam HJ, Schurek KN, Nichol KA, et al. Molecular characterization of increasing fluoroquinolone resistance in Streptococcus pneumoniae isolates in Canada, 1997 to 2005. Antimicrobial Agent and Chemoter 2007; 51: 198-207.
6. Dela campa AJ, Ardanuy C, Balsalobre L, et al. Changes in Fluoroquinolone-Resistant Streptococcus pneumonia after 7-Valent Conjugate Vaccination, Spain. Emerg Infect Dis 2009; 15:905-11.
7. Linares J, Ardauny C, Pallares R, et al. Changes in antimicrobial resistance serotypes and genotypes in Streptococcus pneumoniae over a 30-year period. Clin Microbiol Infect 2010; 16:402-10.
8. Kargar M, Baghernejad M, Ghorbani-daline S, et al. Evaluation of molecular mechanisms resistance to macrolides by Streptococcus pneumoniae strains isolated from Nemazee and Shahid Faghihi Hospitals in Shiraz. Sci J Kurdistan Univ Med Sci 2012: 16(4):83-91.
9. Ip M, Chau SS, Chi F, et al. Rapid screening of fluoroquinolone resistance determinants in Streptococcus pneumoniae by PCR-Restriction Fragment Length Polymorphism and single-strand conformational polymorphism. J Clin Microbiol 2006; 44: 970-5.
10. Fuller JD, Low DE. A review of Streptococcus pneumoniae infection treatment failures associated with fluoroquinolone resistance. Clin Infect Dis 2005; 41:118-21.
11. El-Mahmood A, Isa H, Mohammed A, et al. Antimicrobial susceptibility of some respiratory tract pathogens to commonly used antibiotics at the specialist Hospital, Yola, Adamawa State, Nigeria. J Clin Med Res 2010; 2:135-42.
12. Rodriguez I, Ramos B, Rios E, et al. Clonal spread of levofloxacin-resistance Streptococcus pneumonia invasive isolates in Madrid, spain, 2007 to 2009. Antimicrobial Agent and Chemoter 2011; 55:2469-71.
13. Orr D, Wilkinson P, Moyce L, et al. Incidence and epidemiology of levofloxacin resistance in Streptococcus pneumonia: experience from a tertiary referral hospital in England. J Antimicrobial chemother 2010; 65:449-52.
14. DeVecchi E, Nicola L, Ossola F, et al. In vitro Selection of Resistance in Streptococcus pneumoniae at In vivo fluoroquinolone concentrations. J Antimicrob Chemother 2009; 63:712-27.
15. Brueggeman AB, Coffman SL, Rhomberg P, et al. fluoroquinolone resistance in Streptococcus pneumoniae in United States since 1994-1995. Antimicrobial agent and chemother 2002; 46:680-8.
16. Doern GV, Richte SS, Miller A, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain anti microbial classes?. Clin Infect Dis 2005; 41:139-48.
17. Balsalobre L, Adela G. Fitness of Streptococcus pneumoniae fluoroquinolone-resistance strains with Topoisomerase IV recombinant genes. Antimicrob Agent chemother 2008; 52:822-30.
18. Weigel LM, Anderson GJ, Facklam RR, et al. Geneticanalyses of mutations contributing to fluoroquinolone resistanc in clinical isolates of Streptococcus pneumonia. Antimicrob Agents Chemother 2001; 45:3517-23.
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Issue | Vol 8 No 1-2 (2019) | |
Section | Original Articles | |
Keywords | ||
parC parE Quinolones resistance Streptococcus pneumoniae Topoisomerase IV. |
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