antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-501Research ArticleОБЗОРЫREVIEWSБиологические свойства некоторых низкомолекулярныгх ароматических микробных метаболитов, ассоциированных с сепсисомBiological Properties of Some Sepsis-Associated Low Molecular Aromatic Microbial MetabolitesБелобородоваН. В.BeloborodovaN. V.noemail@neicon.ruОсиповА. А.OsipovA. A.noemail@neicon.ruБедоваА. Ю.BedovaA. Yu.noemail@neicon.ruНИИ общей реаниматологии им. В.А. Неговского РАМНРоссияV.A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical SciencesRussian Federation201313052020587-84861Copyright © ООО «Издательство ОКИ», 20202020ООО «Издательство ОКИ»ООО «Издательство ОКИ»https://www.antibiotics-chemotherapy.ru/jour/about/submissions#copyrightNoticehttps://www.antibiotics-chemotherapy.ru/jour/article/view/501

В обзоре обобщены и проанализированы физико-химические и биологические свойства низкомолекулярных ароматических соединений, ассоциированных с сепсисом. Показано, что такие фенилкарбоновые кислоты (ФКК), как пара-гидроксифенилмолочная (п-ГФМК), фенилмолочная (ФМК), пара-гидроксифенилуксусная (п-ГФУК), фенилуксусная (ФУК), бензойная (БК) и фенилпропионовая (ФПК), обладают биорегуляторной активностью и способны влиять как на бактерии, так и на эукариотические клетки. В обзоре приведены данные о диагностической и патогенетической значимости ФКК, обобщены сведения о микробостатических и микробоцидных свойствах ФКК, биосинтезе ФКК клинически значимыми видами бактерий, описаны механизмы устойчивости микроорганизмов к ФКК, пути метаболизма ФКК прокариотами, мембранный транспорт и пути выведения ФКК из организма человека, а также приведены данные по применению ФКК в клинической практике. Авторы рассматривают ФКК микробного происхождения в качестве участников метаболических и сигнальных путей в процессе интеграции микробиома и человека. На основании данных литературы и результатов собственных исследований авторы обосновывают гипотезу о возможности создания новых лечебных стратегий, основанных на регуляции локального и системного баланса ароматических микробных метаболитов в организме человека.

Physico-chemical and biological properties of sepsis-associated low molecular aromatic compounds are summarized and analysed in the review. Phenylcarbonic acids (PCAs), such as para-hydroxyphenyllactic acid (p-HPLA), phenyllactic acid (PLA), para-hydroxyphenylacetic (p-HPAA), phenylacetic acid (PAA), benzoic acid (BA), and phenylpropionic acid (PPA) are shown to have biorequlatory activity and be able to affect both bacteria and eukaryotic cells. In the review there are presented data on the diagnostic and pathogenetic value of PCAs, their bacteriostatic and bacteriocidal properties and biosynthesis by clinically significant bacterial species, as well as description of the mechanisms of microbial resistance to PCAs, the pathways of PCAs metabolism by prokaryotes, PCAs membrane transport and excretion pathways in humans, the data on the use of PCAs in clinical practice. The authors are of the opinion that PCAs of microbial origin share the metabolic and signal pathways in integration of the microbiome and man. On the basis of the literature data and personal studies the authors validated the hypothesis of possible development of new therapeutic strategies, grounded on regulation of the local and systemic balance of aromatic microbial metabolites in the human body.

низкомолекулярные фенольные соединенияароматические микробные метаболитыметаболический профильбензойная кислотафенилкарбоновые кислотымикробиоммонокарбоксилатные транспортёрысепсисклиническая микроэкологияlow molecular pnenol compoundsaromatic microbial metabolitesmetabolic profilebenzoic acidphenylcarbonic acidsmicrobiomemonocarboxylate transporterssepsisclinical microecologyReferencesDellinger R.P., Levy M.M., Rhodes A., Annane D., Gerlach H., Opal S.M. et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41: 2: 580-637.Dellinger R.P., Levy M.M., Rhodes A., Annane D., Gerlach H., Opal S.M. et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41: 2: 580-637.Angus D.C., Linde-Zwirbl W.T., Lidicker J., Clermont G., Carcillo J., Pinsky M.R. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29: 7: 1303-1310.Angus D.C., Linde-Zwirbl W.T., Lidicker J., Clermont G., Carcillo J., Pinsky M.R. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29: 7: 1303-1310.Хубутия М.Ш., Шабанов А.К., Черненькая Т.В., Годков М.А., Дорфман А.Г. Инфекционные лёгочные осложнения в реанимации и интенсивной терапии у пострадавших с сочетанной травмой. Общая реаниматология 2011; 7: 4: 24-27.Хубутия М.Ш., Шабанов А.К., Черненькая Т.В., Годков М.А., Дорфман А.Г. Инфекционные лёгочные осложнения в реанимации и интенсивной терапии у пострадавших с сочетанной травмой. Общая реаниматология 2011; 7: 4: 24-27.Мороз В.В., Лукач В.Н., Шифман Е.М., Долгих В.Т., Яковлева И.И. Сепсис: клинико-патофизиологические аспекты интенсивной терапии: руководство для врачей. Петрозаводск: ИнтелТек; 2004.Мороз В.В., Лукач В.Н., Шифман Е.М., Долгих В.Т., Яковлева И.И. Сепсис: клинико-патофизиологические аспекты интенсивной терапии: руководство для врачей. Петрозаводск: ИнтелТек; 2004.Руднов В.А., Бельский Д.В., Дехнич А.В. Инфекции в ОРИТ России: результаты национального многоцентрового исследования. Клин. микробиол. антимикроб. химиотер. 2011; 13: 4: 294-303.Руднов В.А., Бельский Д.В., Дехнич А.В. Инфекции в ОРИТ России: результаты национального многоцентрового исследования. Клин. микробиол. антимикроб. химиотер. 2011; 13: 4: 294-303.Белобородова Н.В. Интеграция метаболизма человека и его микробиома при критических состояниях. Общая реаниматол. 2012; 8: 4: 42-54.Белобородова Н.В. Интеграция метаболизма человека и его микробиома при критических состояниях. Общая реаниматол. 2012; 8: 4: 42-54.Rutherford S.T., Bassler B.L. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med 2012; 2: 11: a012427.Rutherford S.T., Bassler B.L. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med 2012; 2: 11: a012427.Шпаков.A.O. Сигнальные пути бактерий непептидной природы QS-типа. Микробиология 2009; 78: 2: 163-175.Шпаков.A.O. Сигнальные пути бактерий непептидной природы QS-типа. Микробиология 2009; 78: 2: 163-175.Lyte M., Vulchanova L., Brown D.R. Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res 2011; 343: 1: 23-32.Lyte M., Vulchanova L., Brown D.R. Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res 2011; 343: 1: 23-32.Белобородова Н.В., Оленин А.Ю., Ходакова A.C., Черневская E.A., Хабиб О.Н. Происхождение и клиническое значение низкомолекулярных фенольных метаболитов в сыворотке крови человека. Анестезиол. реаниматол. 2012; 5: 65-72.Белобородова Н.В., Оленин А.Ю., Ходакова A.C., Черневская E.A., Хабиб О.Н. Происхождение и клиническое значение низкомолекулярных фенольных метаболитов в сыворотке крови человека. Анестезиол. реаниматол. 2012; 5: 65-72.Белобородова Н.В., Возиян А.Ю., Осипов А.А. Лабораторная диагностика бактериальной интоксикации методом газохроматографического анализа крови. Клин. лаб. диагн. 2012; 9: 79.Белобородова Н.В., Возиян А.Ю., Осипов А.А. Лабораторная диагностика бактериальной интоксикации методом газохроматографического анализа крови. Клин. лаб. диагн. 2012; 9: 79.Белобородова Н.В., Архипова A.C., Белобородов Д.М., Бойко Н.Б., Мелько А.И., Оленин А.Ю. Хроматомасс-спектрометрическое определение низкомолекулярных ароматических соединений микробного происхождения в сыворотке крови больных сепсисом. Клин. лаб. диагн. 2006; 2: 3-6.Белобородова Н.В., Архипова A.C., Белобородов Д.М., Бойко Н.Б., Мелько А.И., Оленин А.Ю. Хроматомасс-спектрометрическое определение низкомолекулярных ароматических соединений микробного происхождения в сыворотке крови больных сепсисом. Клин. лаб. диагн. 2006; 2: 3-6.Khodakova A.S., Beloborodova N.V. Microbial metabolites in the blood ofpatients with sepsis. Critical Care 2007; 11: Suppl 4: 5.Khodakova A.S., Beloborodova N.V. Microbial metabolites in the blood ofpatients with sepsis. Critical Care 2007; 11: Suppl 4: 5.Белобородова Н.В., Ходакова А.С., Байрамов И.Т., Оленин А.Ю. Микробный путь образования фенилкарбоновых кислот в организме человека. Биохимия 2009; 74: 12: 1657-1663.Белобородова Н.В., Ходакова А.С., Байрамов И.Т., Оленин А.Ю. Микробный путь образования фенилкарбоновых кислот в организме человека. Биохимия 2009; 74: 12: 1657-1663.Davidson P.M., Sofos J.N., Branen A.L. Editors. Antimicrobials in food. 3rd ed. London: Taylor & Francis Group; 2005.Davidson P.M., Sofos J.N., Branen A.L. Editors. Antimicrobials in food. 3rd ed. London: Taylor & Francis Group; 2005.Lavermicocca P., Valerio F., Evidente A., Lazzaroni S., Corsetti A., Gobbetti M. Purification and characterization of novel antifungal compounds from the sourdough Lactobacillus plantarum strain 21B. Appl Environ Microbiol 2000; 66: 9: 4084-4090.Lavermicocca P., Valerio F., Evidente A., Lazzaroni S., Corsetti A., Gobbetti M. Purification and characterization of novel antifungal compounds from the sourdough Lactobacillus plantarum strain 21B. Appl Environ Microbiol 2000; 66: 9: 4084-4090.Hazelwood L.A., Tai S.L., Boer V.M., de Winde J.H., Pronk J.T., Daran J.M. A new physiological role for Pdr12p in Saccharomyces cerevisiae: export of aromatic and branched-chain organic acids produced in amino acid catabolism. FEMS Yeast Res 2006; 6: 6: 937-945.Hazelwood L.A., Tai S.L., Boer V.M., de Winde J.H., Pronk J.T., Daran J.M. A new physiological role for Pdr12p in Saccharomyces cerevisiae: export of aromatic and branched-chain organic acids produced in amino acid catabolism. FEMS Yeast Res 2006; 6: 6: 937-945.World Health Organization. Concise International Chemical Assessment Document 26. Benzoic acid and sodium benzoate. Geneva: 2000.World Health Organization. Concise International Chemical Assessment Document 26. Benzoic acid and sodium benzoate. Geneva: 2000.Sieber R., Biitikofer U., Bosse J.O. Benzoic acid as a natural compound in cultured dairy products and cheese. Int Dairy J 1995; 5: 227-246.Sieber R., Biitikofer U., Bosse J.O. Benzoic acid as a natural compound in cultured dairy products and cheese. Int Dairy J 1995; 5: 227-246.Kaskoniene V., Maruska A., Kornysova O., Charczun N., Ligor M., Buszewski B. Quantitative and qualitative determination of phenolic compounds in honey. Chemine Technologija. 2009; 3: 52: 74-80.Kaskoniene V., Maruska A., Kornysova O., Charczun N., Ligor M., Buszewski B. Quantitative and qualitative determination of phenolic compounds in honey. Chemine Technologija. 2009; 3: 52: 74-80.Tjakko S., Maria Angela L. de A. Amazonas., Giller V. Characterisation of flavour and taste compounds in Agaricus blazei Murrill sensu Heinem., the cultivated almond mushroom. Australasian Mycologist 2004; 22: 3: 116-122.Tjakko S., Maria Angela L. de A. Amazonas., Giller V. Characterisation of flavour and taste compounds in Agaricus blazei Murrill sensu Heinem., the cultivated almond mushroom. Australasian Mycologist 2004; 22: 3: 116-122.Pappas E., Schaich K.M. Phytochemicals of cranberries and cranberry products: characterization, potential health effects, and processing stability. Crit Rev Food Sci Nutr 2009; 49: 9: 741-781.Pappas E., Schaich K.M. Phytochemicals of cranberries and cranberry products: characterization, potential health effects, and processing stability. Crit Rev Food Sci Nutr 2009; 49: 9: 741-781.Russel N.J., Could G.W. ed. Food Preservatives. 2nd ed. NY: Springer; 2003.Russel N.J., Could G.W. ed. Food Preservatives. 2nd ed. NY: Springer; 2003.Белозерова H.C. Влияние цитокинов и салициловой кислоты на экспрессию генов митохондриальных белков. М.: ФГБУ «ИФР» РАН; 1-150.Белозерова H.C. Влияние цитокинов и салициловой кислоты на экспрессию генов митохондриальных белков. М.: ФГБУ «ИФР» РАН; 1-150.Moore K., Rao P.V., Towers G.H. Degradation of phenylalanine and tyrosine by Sporobolomyces roseus. Biochem J 1968; 106: 2: 507-514.Moore K., Rao P.V., Towers G.H. Degradation of phenylalanine and tyrosine by Sporobolomyces roseus. Biochem J 1968; 106: 2: 507-514.Andersen A. Final report on the safety assessment of benzaldehyde. Int J Toxicol 2006; 25: Suppl 1: 11-27.Andersen A. Final report on the safety assessment of benzaldehyde. Int J Toxicol 2006; 25: Suppl 1: 11-27.European commission health & consumer protection directorate-general. Opinion of the scientific committee on food on benzyl alcohol. Brussel: 2002.European commission health & consumer protection directorate-general. Opinion of the scientific committee on food on benzyl alcohol. Brussel: 2002.Lord S.R., Bralley J.A. Clinical applications of urinary organic acids. Part 2. Dysbiosis Markers. Altern Med Rev 2008; 13: 4: 292-306.Lord S.R., Bralley J.A. Clinical applications of urinary organic acids. Part 2. Dysbiosis Markers. Altern Med Rev 2008; 13: 4: 292-306.Grün C.H., van Dorsten F.A., Jacobs D.M., Le Belleguic M., van Velzen E.J., Bingham M.O. et al. GC-MS methods for metabolic profiling of microbial fermentation products of dietary polyphenols in human and in vitro intervention studies. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 871: 2: 212-219.Grün C.H., van Dorsten F.A., Jacobs D.M., Le Belleguic M., van Velzen E.J., Bingham M.O. et al. GC-MS methods for metabolic profiling of microbial fermentation products of dietary polyphenols in human and in vitro intervention studies. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 871: 2: 212-219.Knoop F. Der Abbau aromatischer Fettsäuren im Tierkörper. Beitr Chem Physiol Pathol 1904; 6: 150-162.Knoop F. Der Abbau aromatischer Fettsäuren im Tierkörper. Beitr Chem Physiol Pathol 1904; 6: 150-162.Jenner A.M., Rafter J., Halliwell B. Human fecal water content of phenolics: the extent of colonic exposure to aromatic compounds. Free Radic Biol Med 2005; 38: 6: 763-772.Jenner A.M., Rafter J., Halliwell B. Human fecal water content of phenolics: the extent of colonic exposure to aromatic compounds. Free Radic Biol Med 2005; 38: 6: 763-772.Khan R.I., Onodera R., Amin M.R., Mohammed N. Aromatic amino acid biosynthesis and production of related compounds from p-hydroxyphenylpyruvic acid by rumen bacteria, protozoa and their mixture. Amino Acids 2002; 22: 2: 167-177.Khan R.I., Onodera R., Amin M.R., Mohammed N. Aromatic amino acid biosynthesis and production of related compounds from p-hydroxyphenylpyruvic acid by rumen bacteria, protozoa and their mixture. Amino Acids 2002; 22: 2: 167-177.Knarreborg A., Miquel N., Granli T., Jensen B.B. Establishment and application of an in vitro methodology to study the effects of organic acids on coliform and lactic acid bacteria in the proximal part of the gastrointestinal tract of piglets. Anim Feed Sci Technol 2002; 99: 131-140.Knarreborg A., Miquel N., Granli T., Jensen B.B. Establishment and application of an in vitro methodology to study the effects of organic acids on coliform and lactic acid bacteria in the proximal part of the gastrointestinal tract of piglets. Anim Feed Sci Technol 2002; 99: 131-140.Cueva C., Moreno-Arribas M.V., Martn-Alvarez P.J., Bills G., Vicente M.F., Basilio A. et al. Antimicrobial activity ofphenolic acids commensal, probiotic and pathogenic bacteria. Res Microbiol 2010; 161: 5: 372-382.Cueva C., Moreno-Arribas M.V., Martn-Alvarez P.J., Bills G., Vicente M.F., Basilio A. et al. Antimicrobial activity ofphenolic acids commensal, probiotic and pathogenic bacteria. Res Microbiol 2010; 161: 5: 372-382.Glass A.D. Influence of phenolic acids on ion uptake: IV. Depolarization of membrane potentials. Plant Physiol 1974; 54: 6: 855-858.Glass A.D. Influence of phenolic acids on ion uptake: IV. Depolarization of membrane potentials. Plant Physiol 1974; 54: 6: 855-858.Beloborodova N., Bairamov I., Olenin A., Shubina V., Teplova V., Fedotcheva N. Effect of phenolic acids of microbial origin on production of reactive oxygen species in mitochondria and neutrophils. J Biomed Sci 2012; 19: 89.Beloborodova N., Bairamov I., Olenin A., Shubina V., Teplova V., Fedotcheva N. Effect of phenolic acids of microbial origin on production of reactive oxygen species in mitochondria and neutrophils. J Biomed Sci 2012; 19: 89.Gerez C.L., Torres M.J., Font de Valdez G., Rollán G. Control of spoilage fungi by lactic acid bacteria. Biological Control 2012; 64: 231-237.Gerez C.L., Torres M.J., Font de Valdez G., Rollán G. Control of spoilage fungi by lactic acid bacteria. Biological Control 2012; 64: 231-237.Suskovic J., Kos B., Beganovic J., Pavunc A.L., Habjanic K., Matosic S. Antimicrobial activity of lactic acid bacteria. Food Technol Biotechnol 2010; 48: 3: 296-307.Suskovic J., Kos B., Beganovic J., Pavunc A.L., Habjanic K., Matosic S. Antimicrobial activity of lactic acid bacteria. Food Technol Biotechnol 2010; 48: 3: 296-307.Valerio F., Lavermicocca P., Pascale M., Visconti A. Production of phenyllactic acid by lactic acid bacteria: an approach to the selection of strains contributing to food quality and preservation. FEMS Microbiol Lett 2004; 233: 2: 289-295.Valerio F., Lavermicocca P., Pascale M., Visconti A. Production of phenyllactic acid by lactic acid bacteria: an approach to the selection of strains contributing to food quality and preservation. FEMS Microbiol Lett 2004; 233: 2: 289-295.Lavermicocca P., Valerio F., Visconti A. Antifungal activity of phenyllactic acid against molds isolated from bakery products. Appl Environ Microbiol 2000; 69: 1: 634-640.Lavermicocca P., Valerio F., Visconti A. Antifungal activity of phenyllactic acid against molds isolated from bakery products. Appl Environ Microbiol 2000; 69: 1: 634-640.Dieuleveux V., Lemarinier S., Gueguen M. Antimicrobial spectrum and target site of D-3-phenyllactic acid. Int J Food Microbiol 1998; 40: 3: 177-183.Dieuleveux V., Lemarinier S., Gueguen M. Antimicrobial spectrum and target site of D-3-phenyllactic acid. Int J Food Microbiol 1998; 40: 3: 177-183.Gabel L.F. The relative action of preservatives in pharmaceutical preparations. J Am Pharm Assoc 1921; 10: 10: 767-768.Gabel L.F. The relative action of preservatives in pharmaceutical preparations. J Am Pharm Assoc 1921; 10: 10: 767-768.Cruess W.V., Richert P.H. Effect of hydrogen ion concentration on the toxicity of sodium benzoate to microorganisms. J Bacteriol 1929; 17: 5: 363-371.Cruess W.V., Richert P.H. Effect of hydrogen ion concentration on the toxicity of sodium benzoate to microorganisms. J Bacteriol 1929; 17: 5: 363-371.Warth A.D. Transport of benzoic and propanoic acids by Zygosaccharomyces bailii. Journal of General Microbiology 1989; 135: 5: 1383-1390.Warth A.D. Transport of benzoic and propanoic acids by Zygosaccharomyces bailii. Journal of General Microbiology 1989; 135: 5: 1383-1390.Mollapour M., Piper P.W. The ZbYME2 gene from the food spoilage yeast Zygosaccharomyces bailii confers not only YME2 functions in Saccharomyces cerevisiae, but also the capacity for catabolism of sorbate and benzoate, two major weak organic acid preservatives. Mol Microbiol 2001; 42: 4: 919-930.Mollapour M., Piper P.W. The ZbYME2 gene from the food spoilage yeast Zygosaccharomyces bailii confers not only YME2 functions in Saccharomyces cerevisiae, but also the capacity for catabolism of sorbate and benzoate, two major weak organic acid preservatives. Mol Microbiol 2001; 42: 4: 919-930.Verduyn C., Postma E., Scheffers W.A., Van Dijken J.P. Effect of benzoic acid on metabolic fluxes in yeasts: a continuous culture study on the regulation of respiration and alcoholic fermentation. Yeast 1992; 8: 7: 501-517.Verduyn C., Postma E., Scheffers W.A., Van Dijken J.P. Effect of benzoic acid on metabolic fluxes in yeasts: a continuous culture study on the regulation of respiration and alcoholic fermentation. Yeast 1992; 8: 7: 501-517.Holyoak C.D., Stratford M., McMullin Z., Cole M.B., Crimmins K., Brown A.J. et al. Activity of the plasma membrane H(+)-ATPase and optimal glycolytic flux are required for rapid adaptation and growth of Saccharomyces cerevisiae in the presence of the weak acid preservative sorbic acid. Appl Environ Microbiol 1996; 62: 9: 3158-3164.Holyoak C.D., Stratford M., McMullin Z., Cole M.B., Crimmins K., Brown A.J. et al. Activity of the plasma membrane H(+)-ATPase and optimal glycolytic flux are required for rapid adaptation and growth of Saccharomyces cerevisiae in the presence of the weak acid preservative sorbic acid. Appl Environ Microbiol 1996; 62: 9: 3158-3164.Holyoak C.D., Bracey D., Piper P.W., Kuchler K., Coote P.J. The Saccharomyces cerevisiae weak acid-inducible ABC transporter Pdr12 transports fluorescein and preservative anions from the cytosol by an energy-dependent mechanism. J Bacteriol 1999; 181: 15: 4644-4652.Holyoak C.D., Bracey D., Piper P.W., Kuchler K., Coote P.J. The Saccharomyces cerevisiae weak acid-inducible ABC transporter Pdr12 transports fluorescein and preservative anions from the cytosol by an energy-dependent mechanism. J Bacteriol 1999; 181: 15: 4644-4652.Krebs H.A., Wiggins D., Stubbs M., Sols A., Bedoya A. Studies on the mechanism of the antifungal action of benzoate. Biochem J 1983; 214: 3: 657-663.Krebs H.A., Wiggins D., Stubbs M., Sols A., Bedoya A. Studies on the mechanism of the antifungal action of benzoate. Biochem J 1983; 214: 3: 657-663.Pearce A.K., Booth I.R., Brown A.J. Genetic manipulation of 6-phosphofructo-1-kinase and fructose 2,6-bisphosphate levels affects the extent to which benzoic acid inhibits the growth of Saccharomyces cerevisiae. Microbiology 2001; 147: Pt 2: 403-410.Pearce A.K., Booth I.R., Brown A.J. Genetic manipulation of 6-phosphofructo-1-kinase and fructose 2,6-bisphosphate levels affects the extent to which benzoic acid inhibits the growth of Saccharomyces cerevisiae. Microbiology 2001; 147: Pt 2: 403-410.Федотчева Н.И., Теплова В.В., Белобородова Н.В. Участие фенольных кислот микробного происхождения в дисфункции митохондрий при сепсисе. Биол. мембран. 2010; 27: 1: 60-66.Федотчева Н.И., Теплова В.В., Белобородова Н.В. Участие фенольных кислот микробного происхождения в дисфункции митохондрий при сепсисе. Биол. мембран. 2010; 27: 1: 60-66.Merfort I., Heilmann J., Weiss M., Pietta P., Gardana C. Radical scavenger activity of three flavonoid metabolites studied by inhibition of chemiluminescence in human PMNs. Planta Med 1996; 62: 4: 289-292.Merfort I., Heilmann J., Weiss M., Pietta P., Gardana C. Radical scavenger activity of three flavonoid metabolites studied by inhibition of chemiluminescence in human PMNs. Planta Med 1996; 62: 4: 289-292.Limasset B., Ojasoo T., le Doucen C., Dore J.C. Inhibition of chemiluminescence in human PMNs by monocyclic phenolic acids and flavonoids. Planta Med 1999; 65: 1: 23-29.Limasset B., Ojasoo T., le Doucen C., Dore J.C. Inhibition of chemiluminescence in human PMNs by monocyclic phenolic acids and flavonoids. Planta Med 1999; 65: 1: 23-29.Brahmachari S., Jana A., Pahan K. Sodium benzoate, a metabolite of cinnamon and a food additive, reduces microglial and astroglial inflammatory responses. J Immunol 2009; 183: 9: 5917-5927.Brahmachari S., Jana A., Pahan K. Sodium benzoate, a metabolite of cinnamon and a food additive, reduces microglial and astroglial inflammatory responses. J Immunol 2009; 183: 9: 5917-5927.Monagas M., Khan N., Andrés-Lacueva C., Urpí-Sardí M., Vázquez-Agell M., Lamuela-Raventós R.M. et al. Dihydroxylated phenolic acids derived from microbial metabolism reduce lipopolysaccharide-stimulated cytokine secretion by human peripheral blood mononuclear cells. Br J Nutr 2009; 102: 2: 201-206.Monagas M., Khan N., Andrés-Lacueva C., Urpí-Sardí M., Vázquez-Agell M., Lamuela-Raventós R.M. et al. Dihydroxylated phenolic acids derived from microbial metabolism reduce lipopolysaccharide-stimulated cytokine secretion by human peripheral blood mononuclear cells. Br J Nutr 2009; 102: 2: 201-206.Kalbag S.S., Palekar A.G. Sodium benzoate inhibits fatty acid oxidation in rat liver: effect on ammonia levels. Biochem Med Metab Biol 1988; 40: 2: 133-142.Kalbag S.S., Palekar A.G. Sodium benzoate inhibits fatty acid oxidation in rat liver: effect on ammonia levels. Biochem Med Metab Biol 1988; 40: 2: 133-142.Lin J., Smith M.P., Chapin K.C., Baik H.S., Bennett G.N., Foster J.W. Mechanisms of acid resistance in enterohemorrhagic Escherichia coli. Appl Environ Microbiol 1996; 62: 9: 3094-3100.Lin J., Smith M.P., Chapin K.C., Baik H.S., Bennett G.N., Foster J.W. Mechanisms of acid resistance in enterohemorrhagic Escherichia coli. Appl Environ Microbiol 1996; 62: 9: 3094-3100.Lambert L.A., Abshire K., Blankenhorn D., Slonczewski J.L. Proteins induced in Escherichia coli by benzoic acid. J Bacteriol 1997; 179: 23: 7595-7599.Lambert L.A., Abshire K., Blankenhorn D., Slonczewski J.L. Proteins induced in Escherichia coli by benzoic acid. J Bacteriol 1997; 179: 23: 7595-7599.Higgins C.F. ABC transporters: from microorganisms to man. Annu Rev Cell Biol 1992; 8: 67-113.Higgins C.F. ABC transporters: from microorganisms to man. Annu Rev Cell Biol 1992; 8: 67-113.Sterkova J., Poledne R., Hubacek J.A. ATP-binding cassette (ABC) transporters in human metabolism and diseases. Physiol Res 2004; 53: 3: 235-243.Sterkova J., Poledne R., Hubacek J.A. ATP-binding cassette (ABC) transporters in human metabolism and diseases. Physiol Res 2004; 53: 3: 235-243.Higgins C.F. ABC transporters: physiology, structure and mechanism -an overview. Res Microbiol 2001; 152: 3-4: 205-210.Higgins C.F. ABC transporters: physiology, structure and mechanism -an overview. Res Microbiol 2001; 152: 3-4: 205-210.Tamai I., Sai Y., Ono A., Kido Y., Yabuuchi H., Takanaga H. et al. Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol 1999; 51: 10: 1-9.Tamai I., Sai Y., Ono A., Kido Y., Yabuuchi H., Takanaga H. et al. Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol 1999; 51: 10: 1-9.Cong D., Fong A.K., Lee R., Pang K.S. Absorption of benzoic acid in segmental regions of the vascularly perfused rat small intestine preparation. Drug Metab Dispos 2001; 29: 12: 1539-1547.Cong D., Fong A.K., Lee R., Pang K.S. Absorption of benzoic acid in segmental regions of the vascularly perfused rat small intestine preparation. Drug Metab Dispos 2001; 29: 12: 1539-1547.Vellonen K.S., Häkli M., Merezhinskaya N., Tervo T., Honkakoski P., Urtti A. Monocarboxylate transport in human corneal epithelium and cell lines. Eur J Pharm Sci 2010; 39: 4: 241-247.Vellonen K.S., Häkli M., Merezhinskaya N., Tervo T., Honkakoski P., Urtti A. Monocarboxylate transport in human corneal epithelium and cell lines. Eur J Pharm Sci 2010; 39: 4: 241-247.Ganapathy V., Thangaraju M., Gopal E., Martin P.M., Itagaki S., Miyauchi S. et al. Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. AAPS J 2008; 10: 1: 193-199.Ganapathy V., Thangaraju M., Gopal E., Martin P.M., Itagaki S., Miyauchi S. et al. Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. AAPS J 2008; 10: 1: 193-199.Juel C., Halestrap A.P. Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter. J Physiol 1999; 517: Pt 3: 633-642.Juel C., Halestrap A.P. Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter. J Physiol 1999; 517: Pt 3: 633-642.Meredith D., Christian H.C. The SLC16 monocarboxylate transporter family. Xenobiotica 2008; 38: 7-8: 1072-1106.Meredith D., Christian H.C. The SLC16 monocarboxylate transporter family. Xenobiotica 2008; 38: 7-8: 1072-1106.Poole R.C., Halestrap A.P. Transport of lactate and other monocarboxy-lates across mammalian plasma membranes. Am J Physiol 1993; 264: 4 Pt 1: 761-782.Poole R.C., Halestrap A.P. Transport of lactate and other monocarboxy-lates across mammalian plasma membranes. Am J Physiol 1993; 264: 4 Pt 1: 761-782.Kang K.W., Jin M.J., Han H.K. IGF-I receptor gene activation enhanced the expression of monocarboxylic acid transporter 1 in hepatocarcinoma cells. Biochem Biophys Res Commun 2006; 342: 4: 1352-1355.Kang K.W., Jin M.J., Han H.K. IGF-I receptor gene activation enhanced the expression of monocarboxylic acid transporter 1 in hepatocarcinoma cells. Biochem Biophys Res Commun 2006; 342: 4: 1352-1355.Halestrap A.P., Meredith D. The SLC16 gene family from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 2004; 447: 5: 619-628.Halestrap A.P., Meredith D. The SLC16 gene family from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 2004; 447: 5: 619-628.Аливердиева Д.А. Дикарбоксилатные переносчики дрожжей: некоторые особенности структуры и субстратная специфичность. Вест. Дагестан. научн. центра 2008; 32: 21-28.Аливердиева Д.А. Дикарбоксилатные переносчики дрожжей: некоторые особенности структуры и субстратная специфичность. Вест. Дагестан. научн. центра 2008; 32: 21-28.Morris M.E., Felmlee M.A. Overview of the proton-coupled MCT (SLC16A) family of transporters: characterization, function and role in the transport of the drug of abuse gamma-hydroxybutyric acid. AAPS J 2008; 10: 2: 311-321.Morris M.E., Felmlee M.A. Overview of the proton-coupled MCT (SLC16A) family of transporters: characterization, function and role in the transport of the drug of abuse gamma-hydroxybutyric acid. AAPS J 2008; 10: 2: 311-321.Majumdar S., Gunda S., Pal D., Mitra A.K. Functional activity of a monocarboxylate transporter, MCT1, in the human retinal pigmented epithelium cell line, ARPE-19. Mol Pharm 2005; 2: 2: 109-117.Majumdar S., Gunda S., Pal D., Mitra A.K. Functional activity of a monocarboxylate transporter, MCT1, in the human retinal pigmented epithelium cell line, ARPE-19. Mol Pharm 2005; 2: 2: 109-117.Kimura O., Tsukagoshi K., Endo T. Uptake of phenoxyacetic acid derivatives into Caco-2 cells by the monocarboxylic acid transporters. Toxicol Lett 2009; 189: 2: 102-109.Kimura O., Tsukagoshi K., Endo T. Uptake of phenoxyacetic acid derivatives into Caco-2 cells by the monocarboxylic acid transporters. Toxicol Lett 2009; 189: 2: 102-109.Vaidyanathan J.B., Walle T. Cellular uptake and efflux of the tea flavonoid (-)-epicatechin-3-gallate in the human intestinal cell line Caco-2. J Pharmacol Exp Ther 2003; 307: 2: 745-752.Vaidyanathan J.B., Walle T. Cellular uptake and efflux of the tea flavonoid (-)-epicatechin-3-gallate in the human intestinal cell line Caco-2. J Pharmacol Exp Ther 2003; 307: 2: 745-752.Современная микробиология. Прокариоты / Ленгелера Й., Древса Г., Шлегеля Г. М.: Мир; 2009. 1.Современная микробиология. Прокариоты / Ленгелера Й., Древса Г., Шлегеля Г. М.: Мир; 2009. 1.Johnson B.F., Stanier R.Y. Regulation of the β-ketoadipate pathway in Alcaligenes eutrophus. J Bacteriol 1971; 107: 2: 476-485.Johnson B.F., Stanier R.Y. Regulation of the β-ketoadipate pathway in Alcaligenes eutrophus. J Bacteriol 1971; 107: 2: 476-485.Collier L.S., Gaines G.L. 3rd, Neidle E.L. Regulation of benzoate degradation in Acinetobacter sp. strain ADP1 by BenM, a LysR-type transcriptional activator. J Bacteriol 1998; 180: 9: 2493-2501.Collier L.S., Gaines G.L. 3rd, Neidle E.L. Regulation of benzoate degradation in Acinetobacter sp. strain ADP1 by BenM, a LysR-type transcriptional activator. J Bacteriol 1998; 180: 9: 2493-2501.Harayama S., Rekik M., Bairoch A., Neidle E.L., Ornston L.N. Potential DNA slippage structures acquired during evolutionary divergence of Acinetobacter calcoaceticus chromosomal benABC and Pseudomonas putida TOL pWW0 plasmid xylXYZ, genes encoding benzoate dioxygenases. J Bacteriol 1991; 173: 23: 7540-7548.Harayama S., Rekik M., Bairoch A., Neidle E.L., Ornston L.N. Potential DNA slippage structures acquired during evolutionary divergence of Acinetobacter calcoaceticus chromosomal benABC and Pseudomonas putida TOL pWW0 plasmid xylXYZ, genes encoding benzoate dioxygenases. J Bacteriol 1991; 173: 23: 7540-7548.Grund E., Knorr C., Eichenlaub R. Catabolism of benzoate and monohydroxylated benzoates by Amycolatopsis and Streptomyces spp. Appl Environ Microbiol 1990; 56: 5: 1459-1464.Grund E., Knorr C., Eichenlaub R. Catabolism of benzoate and monohydroxylated benzoates by Amycolatopsis and Streptomyces spp. Appl Environ Microbiol 1990; 56: 5: 1459-1464.Anderson A.J., Harvey A.L. Effects of the facilitatory compounds catechol, guanidine, noradrenaline and phencyclidine on presynaptic currents of mouse motor nerve terminals. Naunyn Schmiedebergs Arch Pharmacol 1988; 338: 2: 133-137.Anderson A.J., Harvey A.L. Effects of the facilitatory compounds catechol, guanidine, noradrenaline and phencyclidine on presynaptic currents of mouse motor nerve terminals. Naunyn Schmiedebergs Arch Pharmacol 1988; 338: 2: 133-137.Department of Health and Human Services. Hazardous Substances Data Bank (HSDB). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.Department of Health and Human Services. Hazardous Substances Data Bank (HSDB). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.Catechol (ICSC:0411). Prepared in the context of cooperation between the International Programme on Chemical Safety and the Commission of the European Communities © IPCS. CEC. 2005.Catechol (ICSC:0411). Prepared in the context of cooperation between the International Programme on Chemical Safety and the Commission of the European Communities © IPCS. CEC. 2005.Andersen F.A. Amended final report on the safety assessment of pyrocatechol. International J Toxicology 1997; 16: 1: 11-58.Andersen F.A. Amended final report on the safety assessment of pyrocatechol. International J Toxicology 1997; 16: 1: 11-58.Rather L.J., Knapp B., Haehnel W., Fuchs G. Coenzyme A-dependent aerobic metabolism of benzoate via epoxide formation. J Biol Chem 2010; 285: 27: 20615-10624.Rather L.J., Knapp B., Haehnel W., Fuchs G. Coenzyme A-dependent aerobic metabolism of benzoate via epoxide formation. J Biol Chem 2010; 285: 27: 20615-10624.Harwood C.S., Gibson J. Shedding light on anaerobic benzene ring degradation: a process unique to prokaryotes? J Bacteriol 1997; 179: 2: 301-309.Harwood C.S., Gibson J. Shedding light on anaerobic benzene ring degradation: a process unique to prokaryotes? J Bacteriol 1997; 179: 2: 301-309.Gibson J., Harwood C.S. Metabolic diversity in aromatic compound utilization by anaerobic microbes. Annu Rev Microbiol 2002; 56: 1: 345-369.Gibson J., Harwood C.S. Metabolic diversity in aromatic compound utilization by anaerobic microbes. Annu Rev Microbiol 2002; 56: 1: 345-369.Mohapatra P.K. Textbook of Environmental Biotechnology. New Delhi: I.K. International Publishing House Pvt. Ltd.; 2006.Mohapatra P.K. Textbook of Environmental Biotechnology. New Delhi: I.K. International Publishing House Pvt. Ltd.; 2006.Dakin J.D. The fate of sodium benzoate in the human organism. J Biol Chem 1910; 7: 103-108.Dakin J.D. The fate of sodium benzoate in the human organism. J Biol Chem 1910; 7: 103-108.Граник В.Г. Метаболизм эндогенных соединений. М.: Вузовская книга; 2006.Граник В.Г. Метаболизм эндогенных соединений. М.: Вузовская книга; 2006.Wikoff W.R., Anfora A.T., Liu J., Schultz P.G., Lesley S.A., Peters E.C., Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 2009; 106: 10: 3698-3703.Wikoff W.R., Anfora A.T., Liu J., Schultz P.G., Lesley S.A., Peters E.C., Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 2009; 106: 10: 3698-3703.SIDS Initial Assessment Report for 13th SIAM. Benzoates: Benzoic Acid, Sodium Benzoate, Potassium Benzoate, Benzyl alcohol. 2001.SIDS Initial Assessment Report for 13th SIAM. Benzoates: Benzoic Acid, Sodium Benzoate, Potassium Benzoate, Benzyl alcohol. 2001.Temellini A., Mogavero S., Giulianotti P.C., Pietrabissa A., Mosca F., Pacifici G.M. Conjugation of benzoic acid with glycine in human liver and kidney: a study on the interindividual variability. Xenobiotica 1993; 23: 12: 1427-1433.Temellini A., Mogavero S., Giulianotti P.C., Pietrabissa A., Mosca F., Pacifici G.M. Conjugation of benzoic acid with glycine in human liver and kidney: a study on the interindividual variability. Xenobiotica 1993; 23: 12: 1427-1433.Deguchi T., Takemoto M., Uehara N., Lindup W.E., Suenaga A., Otagiri M. Renal clearance of endogenous hippurate correlates with expression levels of renal organic anion transporters in uremic rats. J Pharmacol Exp Ther 2005; 314: 2: 932-938.Deguchi T., Takemoto M., Uehara N., Lindup W.E., Suenaga A., Otagiri M. Renal clearance of endogenous hippurate correlates with expression levels of renal organic anion transporters in uremic rats. J Pharmacol Exp Ther 2005; 314: 2: 932-938.Mutsaers H.A., van den Heuvel L.P., Ringens L.H., Dankers A.C., Russel F.G., Wetzels J.F., et al. Uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations. PLoS One 2011; 6: 4: e18438.Mutsaers H.A., van den Heuvel L.P., Ringens L.H., Dankers A.C., Russel F.G., Wetzels J.F., et al. Uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations. PLoS One 2011; 6: 4: e18438.Hani E.K., Chan V.L. Expression and characterization of Campylobacter jejuni benzoylglycine amidohydrolase (hippuricase) gene in Escherichia coli. J Bacteriol 1995; 177: 9: 2396-2402.Hani E.K., Chan V.L. Expression and characterization of Campylobacter jejuni benzoylglycine amidohydrolase (hippuricase) gene in Escherichia coli. J Bacteriol 1995; 177: 9: 2396-2402.World Health Organization. Food additive series 37: toxicological evaluation of ceratin food additives: benzyl acetate, benzyl alcohol, benzaldehyde, and benzoic acid and its salts. Geneva: 1996.World Health Organization. Food additive series 37: toxicological evaluation of ceratin food additives: benzyl acetate, benzyl alcohol, benzaldehyde, and benzoic acid and its salts. Geneva: 1996.Clemens P.C., Schünemann M.H., Hoffmann G.F., Kohlschütter A. Plasma concentrations of phenyllactic acid in phenylketonuria. J Inherit Metab Dis 1990; 13: 2: 227-228.Clemens P.C., Schünemann M.H., Hoffmann G.F., Kohlschütter A. Plasma concentrations of phenyllactic acid in phenylketonuria. J Inherit Metab Dis 1990; 13: 2: 227-228.Enns G.M., Berry S.A., Berry G.T., Rhead W.J., Brusilow S.W., Hamosh A. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. N Engl J Med 2007; 356: 22: 2282-2292.Enns G.M., Berry S.A., Berry G.T., Rhead W.J., Brusilow S.W., Hamosh A. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. N Engl J Med 2007; 356: 22: 2282-2292.Green T.P., Mirkin B.L. Sodium benzoate in the treatment of hyperammonemia in newborns. Pediatric Research 1981; 15: 630.Green T.P., Mirkin B.L. Sodium benzoate in the treatment of hyperammonemia in newborns. Pediatric Research 1981; 15: 630.Schiff D., Chan G., Stern L. Fixed drug combinations and the displacement of bilirubin from albumin. Pediatrics 1971; 48: 1: 139-141.Schiff D., Chan G., Stern L. Fixed drug combinations and the displacement of bilirubin from albumin. Pediatrics 1971; 48: 1: 139-141.Mu Y., Lin J., Liu R. Interaction of sodium benzoate with trypsin by spectroscopic techniques. Spectrochim Acta A Mol Biomol Spectrosc 2011; 81: 1: 130-135.Mu Y., Lin J., Liu R. Interaction of sodium benzoate with trypsin by spectroscopic techniques. Spectrochim Acta A Mol Biomol Spectrosc 2011; 81: 1: 130-135.Tremblay G.C., Qureshi I.A. The biochemistry and toxicology of benzoic acid metabolism and its relationship to the elimination of waste nitrogen. Pharmacol Ther 1993; 60: 1: 63-90.Tremblay G.C., Qureshi I.A. The biochemistry and toxicology of benzoic acid metabolism and its relationship to the elimination of waste nitrogen. Pharmacol Ther 1993; 60: 1: 63-90.Praphanphoj V., Boyadjiev S.A., Waber L.J., Brusilow S.W., Geraghty M.T. Three cases of intravenous sodium benzoate and sodium phenylacetate toxicity occurring in the treatment of acute hyperammonaemia. J Inherit Metab Dis 2000; 23: 2: 129-136.Praphanphoj V., Boyadjiev S.A., Waber L.J., Brusilow S.W., Geraghty M.T. Three cases of intravenous sodium benzoate and sodium phenylacetate toxicity occurring in the treatment of acute hyperammonaemia. J Inherit Metab Dis 2000; 23: 2: 129-136.SCCNFP/0532/01, final. Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers. 2002.SCCNFP/0532/01, final. Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers. 2002.Garrabou G., Moren C., Lopez S., Tobias E., Cardellach F., Miro O. et al. The effects of sepsis on mitochondria. J Infect Dis 2012; 205: 3: 392-400.Garrabou G., Moren C., Lopez S., Tobias E., Cardellach F., Miro O. et al. The effects of sepsis on mitochondria. J Infect Dis 2012; 205: 3: 392-400.Protti A., Singer M. Bench-to-bedside review: potential strategies to protect or reverse mitochondrial dysfunction in sepsis-induced organ failure. Crit Care 2006; 10: 5: 228.Protti A., Singer M. Bench-to-bedside review: potential strategies to protect or reverse mitochondrial dysfunction in sepsis-induced organ failure. Crit Care 2006; 10: 5: 228.Russel A.D. Mechanisms of bacterial resistance to non-antibiotics: food additives and food pharmaceutical preservatives. J Appl Bacteriol 1991; 71: 3: 191-201.Russel A.D. Mechanisms of bacterial resistance to non-antibiotics: food additives and food pharmaceutical preservatives. J Appl Bacteriol 1991; 71: 3: 191-201.Borawska M.H., Czechowska S.K., Markiewicz R., Palka, J., Świslocka R., Lewandowski W. Antimicrobial activity and cytotoxicity of picolinic acid and selected picolinates as new potential food preservatives. Pol J Food Nutr Sci 2008; 58: 4: 415-418.Borawska M.H., Czechowska S.K., Markiewicz R., Palka, J., Świslocka R., Lewandowski W. Antimicrobial activity and cytotoxicity of picolinic acid and selected picolinates as new potential food preservatives. Pol J Food Nutr Sci 2008; 58: 4: 415-418.Hsiao C.P., Siebert K.J. Modeling the inhibitory effects of organic acids on bacteria. Int J Food Microbiol 1999; 47: 3: 189-201.Hsiao C.P., Siebert K.J. Modeling the inhibitory effects of organic acids on bacteria. Int J Food Microbiol 1999; 47: 3: 189-201.

The authors declare that there are no conflicts of interest present.