<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">antibiotics</journal-id><journal-title-group><journal-title xml:lang="ru">Антибиотики и Химиотерапия</journal-title><trans-title-group xml:lang="en"><trans-title>Antibiot Khimioter = Antibiotics and Chemotherapy</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0235-2990</issn><publisher><publisher-name>ООО «Издательство ОКИ»</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">antibiotics-258</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL PAPERS</subject></subj-group></article-categories><title-group><article-title>Биологическая стоимость устойчивости Helicobacter pylori к рифампицину</article-title><trans-title-group xml:lang="en"><trans-title>Biological Cost of Helicobacter pylori Rifampicin Resistance</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Момыналиев</surname><given-names>К. Т.</given-names></name><name name-style="western" xml:lang="en"><surname>Momynaliev</surname><given-names>K. T.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Челышева</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Chelysheva</surname><given-names>V. V.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Акопиан</surname><given-names>Т. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Akopian</surname><given-names>T. A.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Селезнева</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Selezneva</surname><given-names>O. V.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Говорун</surname><given-names>В. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Govorun</surname><given-names>V. M.</given-names></name></name-alternatives><email xlink:type="simple">noemail@neicon.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Научно-исследовательский институт физико-химической медицины Федерального агентства по здравоохранению и социальному развитию РФ, Москва</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute of Physico-Chemical Medicine, Moscow</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2009</year></pub-date><pub-date pub-type="epub"><day>13</day><month>05</month><year>2020</year></pub-date><volume>54</volume><issue>9-10</issue><fpage>10</fpage><lpage>15</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; ООО «Издательство ОКИ», 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">ООО «Издательство ОКИ»</copyright-holder><copyright-holder xml:lang="en">ООО «Издательство ОКИ»</copyright-holder><license xlink:href="https://www.antibiotics-chemotherapy.ru/jour/about/submissions#copyrightNotice" xlink:type="simple"><license-p>https://www.antibiotics-chemotherapy.ru/jour/about/submissions#copyrightNotice</license-p></license></permissions><self-uri xlink:href="https://www.antibiotics-chemotherapy.ru/jour/article/view/258">https://www.antibiotics-chemotherapy.ru/jour/article/view/258</self-uri><abstract><p>Для определения биологической стоимости устойчивости H.pylori к рифампицину (РИФ) оценивали частоту возникновения мутантов рифампициноустойчивых (РИФР) клонов микроорганизма при адаптации к офлоксацину и метронидазолу. Было показано, что мутации в rpoB гене, обеспечивающие устойчивость H.pylori к РИФ, имеют биологическую стоимость, которые, однако, скомпенсированы дополнительными мутациями в геноме микроорганизма. Сравнение частоты возникновения мутантов в присутствии метронидазола показало, что в результате приобретённой устойчивости к РИФ меняются адаптационные возможности РИФр клонов H.pylori к метронидазолу. Так, для одного из РИФр клонов было показано существенное увеличение частоты мутирования (&gt;700 раз), а также широкий спектр мутаций, обеспечивающих устойчивость к метронидазолу по сравнению с исходным штаммом H.pylori 26695. Описанные явления могут говорить, с одной стороны, о том, что адаптация к РИФ меняет свойства клетки таким образом, что повышает её способность мутировать, с другой — направленная селекция выявляет гипермутабельные клетки в бактериальной популяции, которые, по-видимому, всегда присутствуют в популяции.</p></abstract><trans-abstract xml:lang="en"><p>The frequence of mutations in the rifampicin resistant (RIFr) clones of microorganisms after adaption to ofloxacin and metronidazole was investigated to estimate the biological cost of H.pylori rifampicin (RIF) resistance. Mutations in rpoB gene responsible for RIF resistance of H.pylori were shown to have biological cost and be compensated by additional mutations in the microorganism genome. Comparison of the mutation frequency in the presence of metroniazole demonstrated that the acquired resistance to RIF resulted in changing of the adaptative capacity of the RIFr clones of H.pylori to metronidazole. Thus, a significant increase of the mutation frequency (&gt; 700 times) in one of the RIFr clones and a broad spectrum of the mutations responsible for resistance to metronidazole vs. the H.pylori initial strain 26695 were observed. The findings could be evident of the fact that the adaptation to RIF changed the properties of the cell on one hand in such a way that its mutation capacity increased and that the target selection on the other hand revealed hypermutable cells, likely usual for the bacterial population.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>устойчивость к рифампицину</kwd><kwd>направленная селекция</kwd><kwd>офлоксацин</kwd><kwd>метронидазол</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Helicobacter pylori</kwd><kwd>Helicobacter pylori</kwd><kwd>rifampicin resistance</kwd><kwd>target selection</kwd><kwd>ofloxacin</kwd><kwd>metronidazole</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Guillemot D. Antibiotic use in humans and bacterial resistance. Curr Opin Microbiol 1999; 2: 494—498.</mixed-citation><mixed-citation xml:lang="en">Guillemot D. Antibiotic use in humans and bacterial resistance. Curr Opin Microbiol 1999; 2: 494—498.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Wichelhaus T.A., Böddinghaus B., Besier S. et al. Biological cost of rifampin resistance from the perspective of Staphylococcus aureus. Antimicrob Agents Chemother 2002; 46: 3381—3385.</mixed-citation><mixed-citation xml:lang="en">Wichelhaus T.A., Böddinghaus B., Besier S. et al. Biological cost of rifampin resistance from the perspective of Staphylococcus aureus. Antimicrob Agents Chemother 2002; 46: 3381—3385.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Austin D. J., Kristinsson K. G., Anderson R. M. The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance. Proc Natl Acad Sci USA. 1999; 96: 1152—1156.</mixed-citation><mixed-citation xml:lang="en">Austin D. J., Kristinsson K. G., Anderson R. M. The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance. Proc Natl Acad Sci USA. 1999; 96: 1152—1156.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Seppala H., Klaukka T., Vuopio-Varkila J. et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. New Engl J Med 1997; 337: 441—446.</mixed-citation><mixed-citation xml:lang="en">Seppala H., Klaukka T., Vuopio-Varkila J. et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. New Engl J Med 1997; 337: 441—446.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Hawkey P. M. Molecular epidemiology of clinically significant antibiotic resistance genes. Br J Pharmacol 2008; 153: 406—413.</mixed-citation><mixed-citation xml:lang="en">Hawkey P. M. Molecular epidemiology of clinically significant antibiotic resistance genes. Br J Pharmacol 2008; 153: 406—413.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Stefani S., Agodi A. Molecular epidemiology of antibiotic resistance. Int J Antimicrob Agents 2000; 13: 143—153.</mixed-citation><mixed-citation xml:lang="en">Stefani S., Agodi A. Molecular epidemiology of antibiotic resistance. Int J Antimicrob Agents 2000; 13: 143—153.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">O'Sullivan D. M., McHugh T. D., Gillespie S. H. Analysis of rpoB and pncA mutations in the published literature: an insight into the role of oxidative stress in Mycobacterium tuberculosis evolution? J Antimicrob Chemother 2005. 55: 674—679.</mixed-citation><mixed-citation xml:lang="en">O'Sullivan D. M., McHugh T. D., Gillespie S. H. Analysis of rpoB and pncA mutations in the published literature: an insight into the role of oxidative stress in Mycobacterium tuberculosis evolution? J Antimicrob Chemother 2005. 55: 674—679.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">O'Neill A. J., Huovinen T., Fishwick C. W., Chopra I. Molecular genetic and structural modelling studies of Staphylococcus aureus RNA polymerase and the fitness of rifampin resistance genotypes in relation to clinical prevalence. Antimicrob Agents Chemother 2006; 50: 298—309.</mixed-citation><mixed-citation xml:lang="en">O'Neill A. J., Huovinen T., Fishwick C. W., Chopra I. Molecular genetic and structural modelling studies of Staphylococcus aureus RNA polymerase and the fitness of rifampin resistance genotypes in relation to clinical prevalence. Antimicrob Agents Chemother 2006; 50: 298—309.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Pfister P., Corti N., Hobbie S. et al. 23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A — G. Proc Natl Acad Sci USA 2005; 102: 5180—5185.</mixed-citation><mixed-citation xml:lang="en">Pfister P., Corti N., Hobbie S. et al. 23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A — G. Proc Natl Acad Sci USA 2005; 102: 5180—5185.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Wolter N., Smith A. M., Farrell D. J. et al. Novel mechanism of resistance to oxazolidinones, macrolides, and chloramphenicol in ribosomal protein L4 of the pneumococcus. Antimicrob Agents Chemother 2005; 49: 3554—3557.</mixed-citation><mixed-citation xml:lang="en">Wolter N., Smith A. M., Farrell D. J. et al. Novel mechanism of resistance to oxazolidinones, macrolides, and chloramphenicol in ribosomal protein L4 of the pneumococcus. Antimicrob Agents Chemother 2005; 49: 3554—3557.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Nilsson A. I., Zorzet A., Kanth A. et al. Reducing the fitness cost of antibiotic resistance by amplification of initiator tRNA genes. Proc Natl Acad Sci USA 2006; 103: 6976—6981.</mixed-citation><mixed-citation xml:lang="en">Nilsson A. I., Zorzet A., Kanth A. et al. Reducing the fitness cost of antibiotic resistance by amplification of initiator tRNA genes. Proc Natl Acad Sci USA 2006; 103: 6976—6981.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Heep M., Beck D., Bayerdorffer E., Lehn N. Rifampin and rifabutin resistance mechanism in Helicobacter pylori. Antimicrob Agents Chemother 1999; 43: 1497—1499.</mixed-citation><mixed-citation xml:lang="en">Heep M., Beck D., Bayerdorffer E., Lehn N. Rifampin and rifabutin resistance mechanism in Helicobacter pylori. Antimicrob Agents Chemother 1999; 43: 1497—1499.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Moore R. A., Beckthold B., Wong S. et al. Nucleotide sequence of the gyrA gene and characterization of ciprofloxacin resistant mutants of Helicobacter pylori. Antimicrob. Agents Chemother. 1995. 39: 107—111.</mixed-citation><mixed-citation xml:lang="en">Moore R. A., Beckthold B., Wong S. et al. Nucleotide sequence of the gyrA gene and characterization of ciprofloxacin resistant mutants of Helicobacter pylori. Antimicrob. Agents Chemother. 1995. 39: 107—111.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Goodwin A., Kersulyte D., Sisson G. et al. Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen insensitive NADPH nitroreductase. Mol Microbiol 1998; 28: 383—393.</mixed-citation><mixed-citation xml:lang="en">Goodwin A., Kersulyte D., Sisson G. et al. Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen insensitive NADPH nitroreductase. Mol Microbiol 1998; 28: 383—393.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Sisson G., Jeong J.Y. , Goodwin A. et al. Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H.pylori rdxA (nitroreductase) gene. J Bacteriol 2000; 182: 5091—5096.</mixed-citation><mixed-citation xml:lang="en">Sisson G., Jeong J.Y. , Goodwin A. et al. Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H.pylori rdxA (nitroreductase) gene. J Bacteriol 2000; 182: 5091—5096.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Ge Z., Taylor D. E. Rapid polymerase chain reaction screening of Helicobacter pylori chromosomal point mutations. Helicobacter 1997; 2: 127—131.</mixed-citation><mixed-citation xml:lang="en">Ge Z., Taylor D. E. Rapid polymerase chain reaction screening of Helicobacter pylori chromosomal point mutations. Helicobacter 1997; 2: 127—131.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Ge Wang, Trevor J. M. Wilson, Qin Jiang, Diane E. Taylor. Spontaneous mutations that confer antibiotic resistance in Helicobacter pylori. Antimicrob Agents Chemother 2001; 45: 727—733.</mixed-citation><mixed-citation xml:lang="en">Ge Wang, Trevor J. M. Wilson, Qin Jiang, Diane E. Taylor. Spontaneous mutations that confer antibiotic resistance in Helicobacter pylori. Antimicrob Agents Chemother 2001; 45: 727—733.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Campbell E. A., Korzheva N., Mustaev A. et al. Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 2001; 104: 901—912.</mixed-citation><mixed-citation xml:lang="en">Campbell E. A., Korzheva N., Mustaev A. et al. Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 2001; 104: 901—912.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Jeong J. Y., Mukhopadhyay A. K., Akada J. K. et al. Roles of FrxA and RdxA nitroreductases of Helicobacter pylori in susceptibility and resistance to metronidazole. J Bacteriol 2001; 183: 5155—5162.</mixed-citation><mixed-citation xml:lang="en">Jeong J. Y., Mukhopadhyay A. K., Akada J. K. et al. Roles of FrxA and RdxA nitroreductases of Helicobacter pylori in susceptibility and resistance to metronidazole. J Bacteriol 2001; 183: 5155—5162.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Jeong J. Y., Mukhopadhyay A.K., Dailidiene D. et al. Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes cause moderate and high-level metronidazole resistance in Helicobacter pylori. J Bacteriol 2000; 182: 5082—5090.</mixed-citation><mixed-citation xml:lang="en">Jeong J. Y., Mukhopadhyay A.K., Dailidiene D. et al. Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes cause moderate and high-level metronidazole resistance in Helicobacter pylori. J Bacteriol 2000; 182: 5082—5090.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Albert T. J., Dailidiene D., Dailide G. et al. Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori. Nature Methods 2005; 2: 951—953.</mixed-citation><mixed-citation xml:lang="en">Albert T. J., Dailidiene D., Dailide G. et al. Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori. Nature Methods 2005; 2: 951—953.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
