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Volume 64, Issue 11

Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in species Free

Abstract

This study aimed to investigate the role of quinolone resistance-determining regions (QRDRs) of DNA gyrase (encoded by and ) and topoisomerase IV (encoded by and ) associated with fluoroquinolone resistance. A total of 114 spp. strains, isolated from clinical female patients with symptomatic infection, were tested for species distribution and susceptibility to four fluoroquinolones. Moreover, we analysed the QRDRs and compared these with 14 ATCC reference strains of spp. serovars to identify mutations that caused antimicrobial resistance. Our study indicated that moxifloxacin was the most effective fluoroquinolone against spp. (MIC range: 0.125–32 μg ml). However, extremely high MICs were estimated for ciprofloxacin (MIC range: 1–256 μg ml) and ofloxacin (MIC range: 0.5–128 μg ml), followed by levofloxacin (MIC range: 0.5–64 μg ml). Seven amino acid substitutions were discovered in GyrB, ParC and ParE, but not in GyrA. Ser-83 → Leu/Trp (C248T/G) in ParC and Arg-448 → Lys (G1343A) in ParE, which were potentially responsible for fluoroquinolone resistance, were observed in 89 (77.2 %) and three (2.6 %) strains, respectively. Pro-462 → Ser (C1384T), Asn-481 → Ser (A1442G) and Ala-493 → Val (C1478T) in GyrB and Met-105 → Ile (G315T) in ParC seemed to be neutral polymorphisms, and were observed and occurred along with the amino acid change of Ser-83 → Leu (C248T) in ParC. Interestingly, two novel mutations of ParC and ParE were independently found in four strains. These observations suggest that amino acid mutation in topoisomerase IV appears to be the leading cause of fluoroquinolone resistance, especially the mutation of Ser-83 → Leu (C248T) in ParC. Moxifloxacin had the best activity against strains with Ser-83 → Leu mutation.

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© 2015 The Authors
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2015-11-01
2024-04-26
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References

  1. Azmi I. J., Khajanchi B. K., Akter F., Hasan T. N., Shahnaij M., Akter M., Banik A., Sultana H., Hossain M. A., other authors. 2014; Fluoroquinolone resistance mechanisms of Shigella flexneri isolated in Bangladesh. PLoS One 9:e102533 [View Article][PubMed]
     [Google Scholar]
  2. Bayraktar M. R., Ozerol I. H., Gucluer N., Celik O. 2010; Prevalence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum in pregnant women. Int J Infect Dis 14:e90–e95 [View Article][PubMed]
     [Google Scholar]
  3. Bebear C. M., Renaudin H., Charron A., Gruson D., Lefrancois M., Bebear C. 2000; In vitro activity of trovafloxacin compared to those of five antimicrobials against mycoplasmas including Mycoplasma hominis and Ureaplasma urealyticum fluoroquinolone-resistant isolates that have been genetically characterized. Antimicrob Agents Chemother 44:2557–2560 [View Article][PubMed]
     [Google Scholar]
  4. Bébéar C. M., Renaudin H., Charron A., Clerc M., Pereyre S., Bébéar C. 2003; DNA gyrase and topoisomerase IV mutations in clinical isolates of Ureaplasma spp. and Mycoplasma hominis resistant to fluoroquinolones. Antimicrob Agents Chemother 47:3323–3325 [View Article][PubMed]
     [Google Scholar]
  5. Beeton M. L., Chalker V. J., Kotecha S., Spiller O. B. 2009; Comparison of full gyrA, gyrB, parC and parE gene sequences between all Ureaplasma parvum and Ureaplasma urealyticum serovars to separate true fluoroquinolone antibiotic resistance mutations from non-resistance polymorphism. J Antimicrob Chemother 64:529–538 [View Article][PubMed]
     [Google Scholar]
  6. De Francesco M. A., Caracciolo S., Bonfanti C., Manca N. 2013; Incidence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum isolated in Brescia, Italy, over 7 years. J Infect Chemother 19:621–627 [View Article][PubMed]
     [Google Scholar]
  7. Glass J. I., Lefkowitz E. J., Glass J. S., Heiner C. R., Chen E. Y., Cassell G. H. 2000; The complete sequence of the mucosal pathogen Ureaplasma urealyticum . Nature 407:757–762 [View Article][PubMed]
     [Google Scholar]
  8. Heggie A. D., Bar-Shain D., Boxerbaum B., Fanaroff A. A., O'Riordan M. A., Robertson J. A. 2001; Identification and quantification of ureaplasmas colonizing the respiratory tract and assessment of their role in the development of chronic lung disease in preterm infants. Pediatr Infect Dis J 20:854–859 [View Article][PubMed]
     [Google Scholar]
  9. Hunjak B., Sabol I., Vojnović G., Fistonić I., Erceg A. B., Peršić Z., Grce M. 2014; Ureaplasma urealyticum and Ureaplasma parvum in women of reproductive age. Arch Gynecol Obstet 289:407–412 [View Article][PubMed]
     [Google Scholar]
  10. Katz B., Patel P., Duffy L., Schelonka R. L., Dimmitt R. A., Waites K. B. 2005; Characterization of ureaplasmas isolated from preterm infants with and without bronchopulmonary dysplasia. J Clin Microbiol 43:4852–4854 [View Article][PubMed]
     [Google Scholar]
  11. Kawai Y., Nakura Y., Wakimoto T., Nomiyama M., Tokuda T., Takayanagi T., Shiraishi J., Wasada K., Kitajima H., other authors. 2015; In vitro activity of five quinolones and analysis of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum clinical isolates from perinatal patients in Japan. Antimicrob Agents Chemother 59:2358–2364 [View Article][PubMed]
     [Google Scholar]
  12. Lu J., Liu M., Wang Y., Pang Y., Zhao Z. 2014; Mechanisms of fluoroquinolone monoresistance in Mycobacterium tuberculosis . FEMS Microbiol Lett 353:40–48 [View Article][PubMed]
     [Google Scholar]
  13. Paralanov V., Lu J., Duffy L. B., Crabb D. M., Shrivastava S., Methé B. A., Inman J., Yooseph S., Xiao L., other authors. 2012; Comparative genome analysis of 19 Ureaplasma urealyticum and Ureaplasma parvum strains. BMC Microbiol 12:88 [View Article][PubMed]
     [Google Scholar]
  14. Robertson J. A., Stemke G. W., Davis J. W. Jr, Harasawa R., Thirkell D., Kong F., Shepard M. C., Ford D. K. 2002; Proposal of Ureaplasma parvum sp. nov. and emended description of Ureaplasma urealyticum (Shepard et al. 1974) Robertson et al. 2001. Int J Syst Evol Microbiol 52:587–597[PubMed] [CrossRef]
     [Google Scholar]
  15. Salmeri M., Valenti D., La Vignera S., Bellanca S., Morello A., Toscano M. A., Mastrojeni S., Calogero A. E. 2012; Prevalence of Ureaplasma urealyticum and Mycoplasma hominis infection in unselected infertile men. J Chemother 24:81–86 [View Article][PubMed]
     [Google Scholar]
  16. Singh P., Jain A., Dixit P., Prakash S., Jaiswal I., Venkatesh V., Singh M. 2015; Prevalence of gyrA and B gene mutations in fluoroquinolone-resistant and -sensitive clinical isolates of Mycobacterium tuberculosis and their relationship with MIC of ofloxacin. J Antibiot (Tokyo) 68:63–66 [View Article][PubMed]
     [Google Scholar]
  17. Waites K. B., Bébéar C. M., Robertson J. A., Talkington D. F., Kenny G. E. 2001; Cumitech 34, Laboratory Diagnosis of Mycoplasmal Infections. Edited by Nolte F. S. Washington, DC: American Society for Microbiology;
     [Google Scholar]
  18. Waites K. B., Katz B., Schelonka R. L. 2005; Mycoplasmas and ureaplasmas as neonatal pathogens. Clin Microbiol Rev 18:757–789 [View Article][PubMed]
     [Google Scholar]
  19. Waites K. B., Duffy L. B., Bébéar C. M., Matlow A., Talkington D. F., Kenny G. E., Totten P. A., Bade D. J., Zheng X., other authors. 2012; Standardized methods and quality control limits for agar and broth microdilution susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum . J Clin Microbiol 50:3542–3547 [View Article][PubMed]
     [Google Scholar]
  20. Xie X., Zhang J. 2006; Trends in the rates of resistance of Ureaplasma urealyticum to antibiotics and identification of the mutation site in the quinolone resistance-determining region in Chinese patients. FEMS Microbiol Lett 259:181–186 [View Article][PubMed]
     [Google Scholar]
  21. Xiao L., Crabb D. M., Duffy L. B., Paralanov V., Glass J. I., Waites K. B. 2012; Chromosomal mutations responsible for fluoroquinolone resistance in Ureaplasma species in the United States. Antimicrob Agents Chemother 56:2780–2783 [CrossRef]
     [Google Scholar]
  22. Xie R., Huo S., Li Y., Chen L., Zhang F., Wu X. 2014; Molecular epidemiological survey on quinolone resistance genotype and phenotype of Escherichia coli in septicemic broilers in Hebei. China. Poult Sci 93:335–339 [View Article][PubMed]
     [Google Scholar]
  23. Zhang J., Kong Y., Feng Y., Huang J., Song T., Ruan Z., Song J., Jiang Y., Yu Y., Xie X. 2014a; Development of a multilocus sequence typing scheme for Ureaplasma . Eur J Clin Microbiol Infect Dis 33:537–544 [View Article][PubMed]
     [Google Scholar]
  24. Zhang J., Kong Y., Ruan Z., Huang J., Song T., Song J., Jiang Y., Yu Y., Xie X. 2014b; Correlation between Ureaplasma subgroup 2 and genitourinary tract disease outcomes revealed by an expanded multilocus sequence typing (eMLST) scheme. PLoS One 9:e104347 [View Article][PubMed]
     [Google Scholar]
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Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species
J. Med. Microbiol. 64, 1315 (2015); https://doi.org/10.1099/jmm.0.000153
/content/journal/jmm/10.1099/jmm.0.000153
/content/journal/jmm/10.1099/jmm.0.000153
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