Biochanin A partially restores the activity of ofloxacin and ciprofloxacin against topoisomerase IV mutation-associated fluoroquinolone-resistant species Free

Abstract

This study aims to investigate the synergistic antimicrobial activity of four phytoalexins in combination with fluoroquinolones against spp., a genus of cell wall-free bacteria that are intrinsically resistant to many available antibiotics, making treatment inherently difficult.

A total of 22 958 urogenital tract specimens were assessed for spp. identification and antimicrobial susceptibility. From these, 31 epidemiologically unrelated strains were randomly selected for antimicrobial susceptibility testing to determine the minimum inhibitory concentration (MIC) of four fluoroquinolones and the corresponding quinolone resistance-determining regions (QRDRs). Synergistic effects between fluoroquinolones and four phytoalexins (reserpine, piperine, carvacrol and biochanin A) were evaluated by fractional inhibitory concentration indices (FICIs).

Analysis of the QRDRs suggested a vital role for the mutation of Ser-83→Leu in ParC in fluoroquinolone-resistant strains, and the occurrence of mutations in QRDRs showed significant associations with the breakpoint of levofloxacin. Moreover, diverse synergistic effects of the four phytoalexins with ofloxacin or ciprofloxacin were observed and biochanin A was able to enhance the antimicrobial activity of fluoroquinolones significantly.

This is the first report of the antimicrobial activity of biochanin A in combination with fluoroquinolones against a pathogenic mycoplasma, and opens up the possibility of using components of biochanin A as a promising therapeutic option for treating antibiotic-resistant spp. infections.

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2017-11-01
2024-03-28
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References

  1. Glass JI, Lefkowitz EJ, Glass JS, Heiner CR, Chen EY et al. The complete sequence of the mucosal pathogen Ureaplasma urealyticum. Nature 2000; 407:757–762 [View Article][PubMed]
    [Google Scholar]
  2. Viscardi RM, Hasday JD. Role of Ureaplasma species in neonatal chronic lung disease: epidemiologic and experimental evidence. Pediatr Res 2009; 65:84R–90 [View Article][PubMed]
    [Google Scholar]
  3. Hunjak B, Sabol I, Vojnović G, Fistonić I, Erceg AB et al. Ureaplasma urealyticum and Ureaplasma parvum in women of reproductive age. Arch Gynecol Obstet 2014; 289:407–412 [View Article][PubMed]
    [Google Scholar]
  4. Waites KB, Katz B, Schelonka RL. Mycoplasmas and Ureaplasmas as neonatal pathogens. Clin Microbiol Rev 2005; 18:757–789 [View Article][PubMed]
    [Google Scholar]
  5. Beeton ML, Chalker VJ, Jones LC, Maxwell NC, Spiller OB. Antibiotic resistance among clinical Ureaplasma isolates recovered from neonates in England and Wales between 2007 and 2013. Antimicrob Agents Chemother 2015; 60:52–56 [View Article][PubMed]
    [Google Scholar]
  6. Ye G, Jiang Z, Wang M, Huang J, Jin G et al. The resistance analysis of Ureaplasma urealyticum and Mycoplasma hominis in female reproductive tract specimens. Cell Biochem Biophys 2014; 68:207–210 [View Article][PubMed]
    [Google Scholar]
  7. Pónyai K, Mihalik N, Ostorházi E, Farkas B, Párducz L et al. Incidence and antibiotic susceptibility of genital mycoplasmas in sexually active individuals in Hungary. Eur J Clin Microbiol Infect Dis 2013; 32:1423–1426 [View Article][PubMed]
    [Google Scholar]
  8. de Francesco MA, Caracciolo S, Bonfanti C, Manca N. Incidence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum isolated in Brescia, Italy, over 7 years. J Infect Chemother 2013; 19:621–627 [View Article][PubMed]
    [Google Scholar]
  9. Leli C, Mencacci A, Bombaci JC, D'Alò F, Farinelli S et al. Prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis in a population of Italian and immigrant outpatients. Infez Med 2012; 20:82–87[PubMed]
    [Google Scholar]
  10. Song J, Qiao Y, Kong Y, Ruan Z, Huang J et al. Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species. J Med Microbiol 2015; 64:1315–1320 [View Article][PubMed]
    [Google Scholar]
  11. Xiao L, Crabb DM, Duffy LB, Paralanov V, Glass JI et al. Chromosomal mutations responsible for fluoroquinolone resistance in Ureaplasma species in the United States. Antimicrob Agents Chemother 2012; 56:2780–2783 [View Article]
    [Google Scholar]
  12. Piccinelli G, Gargiulo F, Biscaro V, Caccuri F, Caruso A et al. Analysis of mutations in DNA gyrase and topoisomerase IV of Ureaplasma urealyticum and Ureaplasma parvum serovars resistant to fluoroquinolones. Infect Genet Evol 2017; 47:64–67 [View Article][PubMed]
    [Google Scholar]
  13. Beeton ML, Chalker VJ, Kotecha S, Spiller OB. 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 2009; 64:529–538 [View Article][PubMed]
    [Google Scholar]
  14. Kamiya Y, Shimada Y, Ito S, Kikuchi M, Yasuda M et al. Analysis of the quinolone-resistance determining region of the gyrA gene and the analogous region of the parC gene in Ureaplasma parvum and Ureaplasma urealyticum detected in first-void urine of men with non-gonococcal urethritis. J Antimicrob Chemother 2013; 68:480–482 [View Article][PubMed]
    [Google Scholar]
  15. Xie X, Zhang J. 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 2006; 259:181–186 [View Article][PubMed]
    [Google Scholar]
  16. Kawai Y, Nakura Y, Wakimoto T, Nomiyama M, Tokuda T et al. 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 2015; 59:pii: AAC.04262-04214 [View Article][PubMed]
    [Google Scholar]
  17. Song T, Ye A, Xie X, Huang J, Ruan Z et al. Epidemiological investigation and antimicrobial susceptibility analysis of ureaplasma species and Mycoplasma hominis in outpatients with genital manifestations. J Clin Pathol 2014; 67:817–820 [View Article][PubMed]
    [Google Scholar]
  18. Gibbons S, Oluwatuyi M, Kaatz GW. A novel inhibitor of multidrug efflux pumps in Staphylococcus aureus. J Antimicrob Chemother 2003; 51:13–17 [View Article][PubMed]
    [Google Scholar]
  19. Zhang D, Hu H, Rao Q, Zhao Z. Synergistic effects and physiological responses of selected bacterial isolates from animal feed to four natural antimicrobials and two antibiotics. Foodborne Pathog Dis 2011; 8:1055–1062 [View Article][PubMed]
    [Google Scholar]
  20. Zhang J, Kong Y, Feng Y, Huang J, Song T et al. Development of a multilocus sequence typing scheme for Ureaplasma. Eur J Clin Microbiol Infect Dis 2014; 33:537–544 [View Article][PubMed]
    [Google Scholar]
  21. Bebear CM, Renaudin H, Charron A, Gruson D, Lefrancois M et al. 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 2000; 44:2557–2560 [View Article][PubMed]
    [Google Scholar]
  22. Odds FC. Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 2003; 52:1 [View Article][PubMed]
    [Google Scholar]
  23. Beeton ML, Spiller OB. Antibiotic resistance among Ureaplasma spp. isolates: cause for concern?. J Antimicrob Chemother 2017; 72:330–337 [View Article][PubMed]
    [Google Scholar]
  24. Fuzi M. Dissimilar fitness associated with resistance to fluoroquinolones influences clonal dynamics of various multiresistant bacteria. Front Microbiol 2016; 7:1017 [View Article][PubMed]
    [Google Scholar]
  25. Dalhoff A. Global fluoroquinolone resistance epidemiology and implictions for clinical use. Interdiscip Perspect Infect Dis 2012; 2012:1–37 [View Article][PubMed]
    [Google Scholar]
  26. Singer AC, Shaw H, Rhodes V, Hart A. Review of antimicrobial resistance in the environment and its relevance to environmental regulators. Front Microbiol 2016; 7:7 [View Article][PubMed]
    [Google Scholar]
  27. Redgrave LS, Sutton SB, Webber MA, Piddock LJ. Fluoroquinolone resistance: mechanisms, impact on bacteria, and role in evolutionary success. Trends Microbiol 2014; 22:438–445 [View Article][PubMed]
    [Google Scholar]
  28. Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 2006; 6:629–640 [View Article][PubMed]
    [Google Scholar]
  29. Yao J, Shang K, Huang J, Ran W, Kashif J et al. Overexpression of an ABC transporter and mutations of GyrA, GyrB, and ParC in contributing to high-level ciprofloxacin resistance in Streptococcus suis type 2. Biosci Trends 2014; 8:84–92 [View Article][PubMed]
    [Google Scholar]
  30. Schmitz FJ, Fluit AC, Lückefahr M, Engler B, Hofmann B et al. The effect of reserpine, an inhibitor of multidrug efflux pumps, on the in-vitro activities of ciprofloxacin, sparfloxacin and moxifloxacin against clinical isolates of Staphylococcus aureus. J Antimicrob Chemother 1998; 42:807–810 [View Article][PubMed]
    [Google Scholar]
  31. Mirza ZM, Kumar A, Kalia NP, Zargar A, Khan IA. Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus. J Med Microbiol 2011; 60:1472–1478 [View Article][PubMed]
    [Google Scholar]
  32. Khan IA, Mirza ZM, Kumar A, Verma V, Qazi GN. Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus aureus. Antimicrob Agents Chemother 2006; 50:810–812 [View Article][PubMed]
    [Google Scholar]
  33. Abreu AC, Mcbain AJ, Simões M. Plants as sources of new antimicrobials and resistance-modifying agents. Nat Prod Rep 2012; 29:1007–1021 [View Article][PubMed]
    [Google Scholar]
  34. Morel C, Stermitz FR, Tegos G, Lewis K. Isoflavones as potentiators of antibacterial activity. J Agric Food Chem 2003; 51:5677–5679 [View Article][PubMed]
    [Google Scholar]
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