1887

Abstract

The purpose of the present study was to analyse mutations in the and genes of and define the possible correlation between these mutations and resistance to levofloxacin (LVX), moxifloxacin (MFX) and gatifloxacin (GAT), based on their MICs. One hundred and forty-two clinical isolates were collected from pulmonary tuberculosis patients in the Moscow region. All strains were tested for drug susceptibility to rifampicin and isoniazid using the BACTEC MGIT 960 System and to ofloxacin (OFX) using the absolute concentration method on solid Lowenstein–Jensen slants. All in all, 68 strains were selected at random (38 strains were resistant and 30 were susceptible to OFX) for further analysis using the TB-BIOCHIP-2 test system and DNA sequence analysis. The MICs of LVX, MFX and GAT for selected strains were determined using the BACTEC MGIT 960 System. Mutations in the gene were observed in 36 out of 38 (94.7 %) OFX-resistant strains. Asn538Asp and Asp500His substitutions in the gene only were found in two (5.3 %) strains. Twenty-nine out of 30 OFX-sensitive strains had no mutations in either gene. One (3.3 %) OFX-sensitive strain carried an Arg485His substitution in . The results of our investigation showed that there is no clear correlation between the type of mutation in the genes and , and the MIC levels of LVX, MFX and GAT for resistant strains. Mutations in and Asn538Asp, and Asp500His substitutions in were associated with cross-resistance of to fluoroquinolones. The substitution Arg485His in does not confer resistance to LVX, MFX and GAT in .

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2013-01-01
2019-11-14
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References

  1. An D. D., Hong Duyen N. T., Lan N. T. N., Hoa D. V., Ha D. T. M., Kiet V. S., Thu D. D. A., Van Vinh Chau N., Dung N. H.. & other authors ( 2009;). Beijing genotype of Mycobacterium tuberculosis is significantly associated with high-level fluoroquinolone resistance in Vietnam. . Antimicrob Agents Chemother 53:, 4835–4839. [CrossRef][PubMed]
    [Google Scholar]
  2. Antonova O. V., Gryadunov D. A., Lapa S. A., Kuz’min A. V., Larionova E. E., Smirnova T. G., Nosova E. Y., Skotnikova O. I., Chernousova L. N.. & other authors ( 2008;). Detection of mutations in Mycobacterium tuberculosis genome determining resistance to fluoroquinolones by hybridization on biological microchips. . Bull Exp Biol Med 145:, 108–113. [CrossRef][PubMed]
    [Google Scholar]
  3. Cui Z., Wang J., Lu J., Huang X., Hu Z.. ( 2011;). Association of mutation patterns in gyrA/B genes and ofloxacin resistance levels in Mycobacterium tuberculosis isolates from East China in 2009. . BMC Infect Dis 11:, 78. [CrossRef][PubMed]
    [Google Scholar]
  4. Delgado M. B., Telenti A.. ( 1996;). Selected PCR Protocols for Emerging Infectious Diseases. Edited by Persing D. H... Washington, DC:: American Society for Microbiology;.
    [Google Scholar]
  5. El Sahly H. M., Teeter L. D., Jost K. C. Jr, Dunbar D., Lew J., Graviss E. A.. ( 2011;). Incidence of moxifloxacin resistance in clinical Mycobacterium tuberculosis isolates in Houston, Texas. . J Clin Microbiol 49:, 2942–2945. [CrossRef][PubMed]
    [Google Scholar]
  6. Feuerriegel S., Cox H. S., Zarkua N., Karimovich H. A., Braker K., Rüsch-Gerdes S., Niemann S.. ( 2009;). Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment. . Antimicrob Agents Chemother 53:, 3353–3356. [CrossRef][PubMed]
    [Google Scholar]
  7. Ginsburg A. S., Grosset J. H., Bishai W. R.. ( 2003;). Fluoroquinolones, tuberculosis, and resistance. . Lancet Infect Dis 3:, 432–442. [CrossRef][PubMed]
    [Google Scholar]
  8. Gryadunov D., Dementieva E., Mikhailovich V., Nasedkina T., Rubina A., Savvateeva E., Fesenko E., Chudinov A., Zimenkov D.. & other authors ( 2011;). Gel-based microarrays in clinical diagnostics in Russia. . Expert Rev Mol Diagn 11:, 839–853. [CrossRef][PubMed]
    [Google Scholar]
  9. Kam K. M., Yip C. W., Cheung T. L., Tang H. S., Leung O. C., Chan M. Y.. ( 2006;). Stepwise decrease in moxifloxacin susceptibility amongst clinical isolates of multidrug-resistant Mycobacterium tuberculosis: correlation with ofloxacin susceptibility. . Microb Drug Resist 12:, 7–11. [CrossRef][PubMed]
    [Google Scholar]
  10. Kim H., Nakajima C., Yokoyama K., Rahim Z., Kim Y. U., Oguri H., Suzuki Y.. ( 2011;). Impact of the E540V amino acid substitution in GyrB of Mycobacterium tuberculosis on quinolone resistance. . Antimicrob Agents Chemother 55:, 3661–3667. [CrossRef][PubMed]
    [Google Scholar]
  11. Lau R. W., Ho P. L., Kao R. Y., Yew W. W., Lau T. C., Cheng V. C., Yuen K. Y., Tsui S. K., Chen X., Yam W. C.. ( 2011;). Molecular characterization of fluoroquinolone resistance in Mycobacterium tuberculosis: functional analysis of gyrA mutation at position 74. . Antimicrob Agents Chemother 55:, 608–614. [CrossRef][PubMed]
    [Google Scholar]
  12. Matrat S., Veziris N., Mayer C., Jarlier V., Truffot-Pernot C., Camuset J., Bouvet E., Cambau E., Aubry A.. ( 2006;). Functional analysis of DNA gyrase mutant enzymes carrying mutations at position 88 in the A subunit found in clinical strains of Mycobacterium tuberculosis resistant to fluoroquinolones. . Antimicrob Agents Chemother 50:, 4170–4173. [CrossRef][PubMed]
    [Google Scholar]
  13. Merle C. S., Sismanidis C., Bah Sow O., Gninafon M., Horton J., Lapujade O., Lo M. B., Mitchinson D. A., Perronne C.. & other authors ( 2012;). A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the gatifloxacin for TB (OFLOTUB) project. . Trials 13:, 61. [CrossRef][PubMed]
    [Google Scholar]
  14. Mokrousov I., Otten T., Manicheva O., Potapova Y., Vishnevsky B., Narvskaya O., Rastogi N.. ( 2008;). Molecular characterization of ofloxacin-resistant Mycobacterium tuberculosis strains from Russia. . Antimicrob Agents Chemother 52:, 2937–2939. [CrossRef][PubMed]
    [Google Scholar]
  15. Order of the Ministry of Health of the Russian Federation ( 2003;). Improvement of tuberculosis-controlling measures in the Russian Federation under no. 109 on March 21 2003, In Russian; last accessed 5 April 2012. http://48rospotrebnadzor.ru/files.aspx?id=1bf0f4ed590545f3b2921079c2669ba8
  16. Pantel A., Petrella S., Matrat S., Brossier F., Bastian S., Reitter D., Jarlier V., Mayer C., Aubry A.. ( 2011;). DNA gyrase inhibition assays are necessary to demonstrate fluoroquinolone resistance secondary to gyrB mutations in Mycobacterium tuberculosis. . Antimicrob Agents Chemother 55:, 4524–4529. [CrossRef][PubMed]
    [Google Scholar]
  17. Pitaksajjakul P., Wongwit W., Punprasit W., Eampokalap B., Peacock S., Ramasoota P.. ( 2005;). Mutations in the gyrA and gyrB genes of fluoroquinolone-resistant Mycobacterium tuberculosis from TB patients in Thailand. . Southeast Asian J Trop Med Public Health 36: (Suppl. 4), 228–237.[PubMed]
    [Google Scholar]
  18. Poissy J., Aubry A., Fernandez C., Lott M. C., Chauffour A., Jarlier V., Farinotti R., Veziris N.. ( 2010;). Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model. . Antimicrob Agents Chemother 54:, 4765–4771. [CrossRef][PubMed]
    [Google Scholar]
  19. Rodríguez J. C., Ruiz M., López M., Royo G.. ( 2002;). In vitro activity of moxifloxacin, levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis. . Int J Antimicrob Agents 20:, 464–467. [CrossRef][PubMed]
    [Google Scholar]
  20. Rüsch-Gerdes S., Pfyffer G. E., Casal M., Chadwick M., Siddiqi S.. ( 2006;). Multicenter laboratory validation of the BACTEC MGIT 960 technique for testing susceptibilities of Mycobacterium tuberculosis to classical second-line drugs and newer antimicrobials. . J Clin Microbiol 44:, 688–692. [CrossRef][PubMed]
    [Google Scholar]
  21. Shi R., Zhang J., Li C., Kazumi Y., Sugawara I.. ( 2006;). Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates from China as determined by gyrA mutation analysis using denaturing high-pressure liquid chromatography and DNA sequencing. . J Clin Microbiol 44:, 4566–4568. [CrossRef][PubMed]
    [Google Scholar]
  22. Siddiqi S., Rusch-Gerdes S.. ( 2007;). MGIT Procedure Manual. For BACTEC MGIT 960 TB System (Also applicable for Manual MGIT), Mycobacteria Growth Indicator Tube (MGIT), Culture and Drug Susceptibility Demonstration Projects. http://www.finddiagnostics.org/export/sites/default/resourcecentre/find_documentation/pdfs/mgit_manual_nov_2007.pdf
  23. Takiff H. E., Salazar L., Guerrero C., Philipp W., Huang W. M., Kreiswirth B., Cole S. T., Jacobs W. R. Jr, Telenti A.. ( 1994;). Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. . Antimicrob Agents Chemother 38:, 773–780. [CrossRef][PubMed]
    [Google Scholar]
  24. van Doorn H. R., An D. D., de Jong M. D., Lan N. T., Hoa D. V., Quy H. T., Chau N. V., Duy P. M., Tho D. Q.. & other authors ( 2008;). Fluoroquinolone resistance detection in Mycobacterium tuberculosis with locked nucleic acid probe real-time PCR. . Int J Tuberc Lung Dis 12:, 736–742.[PubMed]
    [Google Scholar]
  25. Von Groll A., Martin A., Jureen P., Hoffner S., Vandamme P., Portaels F., Palomino J. C., da Silva P. A.. ( 2009;). Fluoroquinolone resistance in Mycobacterium tuberculosis and mutations in gyrA and gyrB. . Antimicrob Agents Chemother 53:, 4498–4500. [CrossRef][PubMed]
    [Google Scholar]
  26. Wang J. Y., Lee L. N., Lai H. C., Wang S. K., Jan I. S., Yu C. J., Hsueh P. R., Yang P. C.. ( 2007;). Fluoroquinolone resistance in Mycobacterium tuberculosis isolates: associated genetic mutations and relationship to antimicrobial exposure. . J Antimicrob Chemother 59:, 860–865. [CrossRef][PubMed]
    [Google Scholar]
  27. Xu P., Li X., Zhao M., Gui X., DeRiemer K., Gagneux S., Mei J., Gao Q.. ( 2009;). Prevalence of fluoroquinolone resistance among tuberculosis patients in Shanghai, China. . Antimicrob Agents Chemother 53:, 3170–3172. [CrossRef][PubMed]
    [Google Scholar]
  28. Yin X., Yu Z.. ( 2010;). Mutation characterization of gyrA and gyrB genes in levofloxacin-resistant Mycobacterium tuberculosis clinical isolates from Guangdong Province in China. . J Infect 61:, 150–154. [CrossRef][PubMed]
    [Google Scholar]
  29. Zhao B. Y., Pine R., Domagala J., Drlica K.. ( 1999;). Fluoroquinolone action against clinical isolates of Mycobacterium tuberculosis: effects of a C-8 methoxyl group on survival in liquid media and in human macrophages. . Antimicrob Agents Chemother 43:, 661–666.[PubMed]
    [Google Scholar]
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