medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-17-168-176medsovet-2715Research ArticleНЕФРОЛОГИЯ / УРОЛОГИЯNEPHROLOGY / UROLOGYОт бактериурии до микробиома мочевых путей: эволюция взглядов ученых и клиницистовFrom bacteriuria to the urinary tract microbiome: the evolution of the views of researchers and cliniciansЗахароваИ. Н.ZakharovaI. N.

Захарова Ирина Николаевна – доктор медицинских наук, заслуженный врач России, заведующая кафедрой педиатрии с курсом поликлинической педиатрии им. академика Г.Н. Сперанского ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» (РМАНПО) МЗ РФ, полный член EAACI, ESPGHAN

Москва

ОсмановИ. М.OsmanovI. M.

Османов Исмаил Магомедович – доктор медицинских наук, профессор, главный внештатный детский специалист-нефролог, главный врач ГБУЗ «ДГКБ им. З.А. Башляевой ДЗ г. Москвы, директор Университетской клиники педиатрии, профессор кафедры госпитальной педиатрии №1 ФГБОУ ВО «РНИМУ им. Н.И. Пирогова»

Москва

МачневаЕ. Б.MachnevaE. В.

Мачнева Елена Борисовна – кандидат медицинских наук, Российская детская клиническая больница (РДКБ)

Москва

МумладзеЭ. Б.MumladzeЕ. B.

Мумладзе Этери Борисовна – кандидат медицинских наук, доцент кафедры педиатрии с курсом поликлинической педиатрии им. ак. Г.Н. Сперанского

Москва

КасьяноваА. Н.KasyanovaA. N.

Касьянова Анна Николаевна – клинический ординатор кафедры педиатрии с курсом поликлинической педиатрии им. академика Г.Н. Сперанского

Москва

АйсановаМ. P.AisanovaM. Р.

Айсанова Марьят Романовна – ординатор кафедры педиатрии с курсом поликлинической педиатрии им. академика Г.Н. Сперанского

Москва

ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияRussian Medical Academy of Continuing Vocational Education of the Ministry of HealthRussian FederationДетская городская клиническая больница им. З.А. Башляевой Департамента здравоохранения г. МосквыРоссияBashlyaeva Children’s City Clinical Hospital of the Moscow Health DepartmentRussian FederationФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияRussian Children’s Clinical Hospital, Pirogov Russian National Research Medical University (RNRMU) of the Ministry of Health of RussiaRussian Federation201821102018017168177Copyright © Захарова И.Н., Османов И.М., Мачнева Е.Б., Мумладзе Э.Б., Касьянова А.Н., Айсанова М.P., 20182018Захарова И.Н., Османов И.М., Мачнева Е.Б., Мумладзе Э.Б., Касьянова А.Н., Айсанова М.P.Zakharova I.N., Osmanov I.M., Machneva E.В., Mumladze Е.B., Kasyanova A.N., Aisanova M.Р.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2715

Сохранение целостности мочевых путей человека при взаимодействии с микроорганизмами зависит от баланса многих составляющих: полноценности неспецифических защитных факторов слизистых мочевых путей, факторов вирулентности микроорганизмов, выраженности врожденного ответа тканей мочевых путей на присутствие микроорганизмов, взаимного воздействия микро- и макроорганизма друг на друга, направленного в сторону формирования нормального микробиома, а не воспаления. Большинство этих факторов генетически детерминированы как со стороны микроорганизмов, так и со стороны человека. В статье представлены современные данные российских и зарубежных литературных источников, посвященных описанию факторов, поддерживающих гомеостаз мочевых путей при взаимодействии с микроорганизмами. Подчеркнуто значение этих данных в практике врача-клинициста, в том числе педиатра и детского нефролога, семейного врача.

The preservation of the human urinary tract integrity in interaction with microorganisms depends on the balance of many components: the viability of nonspecific protective factors of the urinary tract mucosa, the virulence factors of microorganisms, the intensity of the innate immune response of the urinary tract tissue to the presence of microorganisms, the mutual impact of the microand macro-organism upon each other that is directed towards creation of a normal microbiome, and not inflammation. Most of these factors are genetically determined both by microorganisms and humans. The article presents modern data of Russian and foreign literature devoted to the description of factors supporting the homeostasis of the urinary tract in interacting with microorganisms. The authors emphasise a key role of these data in the practice of clinicians, including paediatricians and paediatric nephrologists, family doctors.

инфекция мочевых путейбактериурияуропатогенымикробиом мочигеномцитокиныинтерлейкиныострова патогенностифакторы вирулентностиEscherichia coliToll-подобные рецепторыurinary tract infectionbacteriuriauropathogensurine microbiomegenomecytokinesinterleukinspathogenicity islandsvirulence factorsEscherichia coliToll-like receptorsReferencesStein R, Dogan HS, Hoebeke P et al. Urinary Tract Infections in Children: EAU/ ESPU Guidelines. Eur Urol, 2014 Dec 1. pii: S03022838(14)01181-6.Stein R, Dogan HS, Hoebeke P et al. Urinary Tract Infections in Children: EAU/ ESPU Guidelines. Eur Urol, 2014 Dec 1. pii: S03022838(14)01181-6.Robinson JL, Finlay JC, Lang ME, Bortolussi R. Urinary tract infections in infants and children: Diagnosis and management. Canadian Paediatric Society, Infectious Diseases and Immunization Committee, Community Paediatrics Committee. Paediatr Child Health, 2014 Jun, 19(6): 315-2.Robinson JL, Finlay JC, Lang ME, Bortolussi R. Urinary tract infections in infants and children: Diagnosis and management. Canadian Paediatric Society, Infectious Diseases and Immunization Committee, Community Paediatrics Committee. Paediatr Child Health, 2014 Jun, 19(6): 315-2.Федеральные клинические рекомендации по оказанию медицинской помощи детям с инфекцией мочевыводящих путей. [Электронный ресурс]. М.: Союз педиатров России, 2015. Режим доступа: http: //www.pediatr-russia.ru/sites/default/files/file/kr_imvp.pdfFederal clinical guidelines for medical care of children with urinary tract infection. [Electronic resource]. M.: The Union of Pediatricians of Russia, 2015. Access mode: http: //www.pediatr-russia.ru/sites/default/files/file/kr_imvp.pdfЗахарова И.Н., Османов И.М., Мумладзе Э.Б., Мачнева Е.Б., Тамбиева Е.В., Бекмурзаева Г.Б. Бессимптомная бактериурия: смена общепринятого взгляда. Медицинский совет, 2017, 19: 162-167.Zakharova IN, Osmanov IM, Mumladze EB, Machneva EB, Tambieva EV, Bekmurzaeva GB. Asymptomatic bacteriuria: change of orthodox view. Meditsinsky Sovet, 2017, 19: 162-167.Finucane TE. «Urinary Tract Infection» – Requiem for a Heavyweight. J Am Geriatr Soc, 2017 Aug 65(8): 1650-1655.Finucane TE. «Urinary Tract Infection» – Requiem for a Heavyweight. J Am Geriatr Soc, 2017 Aug 65(8): 1650-1655.Curtiss N, Balachandran A, Krska L, PeppiattWildman C, Wildman S, Duckett J. Age, menopausal status and the bladder microbiome. Eur J Obstet Gynecol Reprod Biol. 2018 Jun 18 228: 126-129.Curtiss N, Balachandran A, Krska L, PeppiattWildman C, Wildman S, Duckett J. Age, menopausal status and the bladder microbiome. Eur J Obstet Gynecol Reprod Biol. 2018 Jun 18 228: 126-129.Komesu YM, Richter HE, Carper B, Dinwiddie DL, Lukacz ES, Siddiqui NY, Sung VW, Zyczynski HM, Ridgeway B, Rogers RG, Arya LA, Mazloomdoost D, Gantz MG. The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls. Int Urogynecol J. 2018 Jun 16. doi: 10.1007/s00192018-3683-6. [Epub ahead of print].Komesu YM, Richter HE, Carper B, Dinwiddie DL, Lukacz ES, Siddiqui NY, Sung VW, Zyczynski HM, Ridgeway B, Rogers RG, Arya LA, Mazloomdoost D, Gantz MG. The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls. Int Urogynecol J. 2018 Jun 16. doi: 10.1007/s00192018-3683-6. [Epub ahead of print].Karstens L, Asquith M, Davin S, Stauffer P, Fair D, Gregory WT, Rosenbaum JT, McWeeney SK, Nardos R. Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity? Front Cell Infect Microbiol, 2016 Jul 27, 6: 78.Karstens L, Asquith M, Davin S, Stauffer P, Fair D, Gregory WT, Rosenbaum JT, McWeeney SK, Nardos R. Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity? Front Cell Infect Microbiol, 2016 Jul 27, 6: 78.Vila J, Saez-Lopez E, Johnson JR, Romling U, Dobrindt U, Canton R, Giske CG, Naas T, Carattoli A, Martinez-Medina M, Bosch J, Retamar P, Rodriguez-Bano J, Baquero F, Soto SM. Escherichia coli: an old friend with new tidings. FEMS Microbiol Rev, 2016 Jul 1, 40(4): 437-463.Vila J, Saez-Lopez E, Johnson JR, Romling U, Dobrindt U, Canton R, Giske CG, Naas T, Carattoli A, Martinez-Medina M, Bosch J, Retamar P, Rodriguez-Bano J, Baquero F, Soto SM. Escherichia coli: an old friend with new tidings. FEMS Microbiol Rev, 2016 Jul 1, 40(4): 437-463.Dobrindt U, Blum-Oehler G, Hartsch T, Gottschalk G, Ron EZ, Funfstuck R, Hacker J. S-Fimbria-Encoding Determinant sfaI Is Located on Pathogenicity Island III536 of Uropathogenic Escherichia coli Strain 536. Infect Immun, 2001 Jul, 69(7): 4248–4256.Dobrindt U, Blum-Oehler G, Hartsch T, Gottschalk G, Ron EZ, Funfstuck R, Hacker J. S-Fimbria-Encoding Determinant sfaI Is Located on Pathogenicity Island III536 of Uropathogenic Escherichia coli Strain 536. Infect Immun, 2001 Jul, 69(7): 4248–4256.Jones CH, Pinkner JS, Roth R, Heuser J, Nicholes AV, Abraham SN, Hultgren SJ. FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae. Proc Natl Acad Sci U S A, 1995 Mar 1, 92(6): 2081-5.Jones CH, Pinkner JS, Roth R, Heuser J, Nicholes AV, Abraham SN, Hultgren SJ. FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae. Proc Natl Acad Sci U S A, 1995 Mar 1, 92(6): 2081-5.Zhou G, Mo WJ, Sebbel P, Min G, Neubert TA, Glockshuber R, Wu XR, Sun TT, Kong XP. Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. J Cell Sci, 2001 Nov, 114(Pt 22): 4095-103.Zhou G, Mo WJ, Sebbel P, Min G, Neubert TA, Glockshuber R, Wu XR, Sun TT, Kong XP. Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. J Cell Sci, 2001 Nov, 114(Pt 22): 4095-103.Xie B, Zhou G, Chan SY, Shapiro E, Kong XP, Wu XR, Sun TT, Costello CE. Distinct glycan structures of uroplakins Ia and Ib: structural basis for the selective binding of FimH adhesin to uroplakin Ia. J Biol Chem, 2006 May 26, 281(21): 14644-53. Epub 2006 Mar 27.Xie B, Zhou G, Chan SY, Shapiro E, Kong XP, Wu XR, Sun TT, Costello CE. Distinct glycan structures of uroplakins Ia and Ib: structural basis for the selective binding of FimH adhesin to uroplakin Ia. J Biol Chem, 2006 May 26, 281(21): 14644-53. Epub 2006 Mar 27.Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J, 2000 Jun 15, 19(12): 2803-12.Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J, 2000 Jun 15, 19(12): 2803-12.Эрман М.В. Фитотерапия в лечении инфекции мочевой системы у детей. Эффективная фармакотерапия, 2014, 16: 18-22.Erman MV. Phytotherapy in the treatment of urinary system infections in children. Effectivnaya Farmakoterapia, 2014, 16: 18-22.Kline KA, Ingersoll MA, Nielsen HV, Sakinc T, Henriques-Normark B, Gatermann S, Caparon MG, Hultgren SJ. Characterization of a novel murine model of Staphylococcus saprophyticus urinary tract infection reveals roles for Ssp and SdrI in virulence. Infect Immun, 2010 May 78(5): 1943-51.Kline KA, Ingersoll MA, Nielsen HV, Sakinc T, Henriques-Normark B, Gatermann S, Caparon MG, Hultgren SJ. Characterization of a novel murine model of Staphylococcus saprophyticus urinary tract infection reveals roles for Ssp and SdrI in virulence. Infect Immun, 2010 May 78(5): 1943-51.Giridhara Upadhyaya PM, Ravikumar KL, Umapathy BL. Review of virulence factors of enterococcus: an emerging nosocomial pathogen. Indian J Med Microbiol, 2009 Oct-Dec, 27(4): 301-5.Giridhara Upadhyaya PM, Ravikumar KL, Umapathy BL. Review of virulence factors of enterococcus: an emerging nosocomial pathogen. Indian J Med Microbiol, 2009 Oct-Dec, 27(4): 301-5.Armbruster CE, Mobley HLT, Pearson MM. Pathogenesis of Proteus mirabilis Infection. EcoSal Plus, 2018 Feb, 8(1): 10.1128/ecosalplus. ESP-0009-2017.Armbruster CE, Mobley HLT, Pearson MM. Pathogenesis of Proteus mirabilis Infection. EcoSal Plus, 2018 Feb, 8(1): 10.1128/ecosalplus. ESP-0009-2017.Behzadi P, Behzadi E, Ranjbar R. Urinary tract infections and Candida albicans. Cent European J Urol, 2015, 68(1): 96–101.Behzadi P, Behzadi E, Ranjbar R. Urinary tract infections and Candida albicans. Cent European J Urol, 2015, 68(1): 96–101.Cegelski L. Bottom-Up and Top-Down SolidState NMR Approaches for Bacterial Biofilm Matrix Composition. J Magn Reson, 2015 Apr, 253: 91–97.Cegelski L. Bottom-Up and Top-Down SolidState NMR Approaches for Bacterial Biofilm Matrix Composition. J Magn Reson, 2015 Apr, 253: 91–97.Ingersoll MA, Albert ML. From infection to immunotherapy: host immune responses to bacteria at the bladder mucosa. Mucosal Immunol, 2013 Nov, 6(6): 1041-53.Ingersoll MA, Albert ML. From infection to immunotherapy: host immune responses to bacteria at the bladder mucosa. Mucosal Immunol, 2013 Nov, 6(6): 1041-53.Wu XR, Kong XP, Pellicer A, Kreibich G, Sun TT. Uroplakins in urothelial biology, function, and disease. Kidney Int, 2009 Jun, 75(11): 1153-65.Wu XR, Kong XP, Pellicer A, Kreibich G, Sun TT. Uroplakins in urothelial biology, function, and disease. Kidney Int, 2009 Jun, 75(11): 1153-65.Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P. The immune geography of IgA induction and function. Mucosal Immunol, 2008, 1: 11–22.Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P. The immune geography of IgA induction and function. Mucosal Immunol, 2008, 1: 11–22.Hans M, Madaan Hans V. Epithelial Antimicrobial Peptides: Guardian of the Oral Cavity. Int J Pept, 2014, 2014: 370297.Hans M, Madaan Hans V. Epithelial Antimicrobial Peptides: Guardian of the Oral Cavity. Int J Pept, 2014, 2014: 370297.Pak J, Pu Y, Zhang ZT, Hasty DL, Wu XR. TammHorsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli frombinding to uroplakin Ia and Ib receptors. J Biol Chem, 2001 Mar 30, 276(13): 9924-30.Pak J, Pu Y, Zhang ZT, Hasty DL, Wu XR. TammHorsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli frombinding to uroplakin Ia and Ib receptors. J Biol Chem, 2001 Mar 30, 276(13): 9924-30.Darouiche RO, Hull RA. Bacterial interference for prevention of urinary tract infection. Clin Infect Dis, 2012, 55: 1400-1407.Darouiche RO, Hull RA. Bacterial interference for prevention of urinary tract infection. Clin Infect Dis, 2012, 55: 1400-1407.Kawai Т, Akira S. Toll-like receptor downstream signaling. Arthritis Res Ther, 2005, 7(1): 12–19.Kawai Т, Akira S. Toll-like receptor downstream signaling. Arthritis Res Ther, 2005, 7(1): 12–19.Yin X, Hou T, Liu Y, Chen J, Yao Z, Ma C, Yang L, Wei L. Association of Toll-like receptor 4 gene polymorphism and expression with urinary tract infection types in adults. PLoS One, 2010 Dec 3, 5(12): e14223.Yin X, Hou T, Liu Y, Chen J, Yao Z, Ma C, Yang L, Wei L. Association of Toll-like receptor 4 gene polymorphism and expression with urinary tract infection types in adults. PLoS One, 2010 Dec 3, 5(12): e14223.Fischer H, Yamamoto M, Akira S, Beutler B, Svanborg C. Mechanism of pathogen-specific TLR4 activation in the mucosa: fimbriae, recognition receptors and adaptor protein selection. Eur J Immunol, 2006 Feb, 36(2): 267-77.Fischer H, Yamamoto M, Akira S, Beutler B, Svanborg C. Mechanism of pathogen-specific TLR4 activation in the mucosa: fimbriae, recognition receptors and adaptor protein selection. Eur J Immunol, 2006 Feb, 36(2): 267-77.Ragnarsdottir B, Samuelsson M, Gustafsson MC, Leijonhufvud I, Karpman D, Svanborg C. Reduced toll-like receptor 4 expression in children with asymptomatic bacteriuria. J Infect Dis, 2007 Aug 1, 196(3): 475-84.Ragnarsdottir B, Samuelsson M, Gustafsson MC, Leijonhufvud I, Karpman D, Svanborg C. Reduced toll-like receptor 4 expression in children with asymptomatic bacteriuria. J Infect Dis, 2007 Aug 1, 196(3): 475-84.Daringer NM, Schwarz KA, Leonard JN. Contributions of Unique Intracellular Domains to Switchlike Biosensing by Toll-like Receptor 4. J Biol Chem, 2015 Apr 3, 290(14): 8764–8777.Daringer NM, Schwarz KA, Leonard JN. Contributions of Unique Intracellular Domains to Switchlike Biosensing by Toll-like Receptor 4. J Biol Chem, 2015 Apr 3, 290(14): 8764–8777.Ambite I, Puthia M, Nagy K, Cafaro C, Nadeem A, Butler DS, Rydstrom G, Filenko NA, Wullt B, Miethke T, Svanborg C. Molecular Basis of Acute Cystitis Reveals Susceptibility Genes and Immunotherapeutic Targets. PLoS Pathog, 2016 Oct 12, 12(10): e1005848.Ambite I, Puthia M, Nagy K, Cafaro C, Nadeem A, Butler DS, Rydstrom G, Filenko NA, Wullt B, Miethke T, Svanborg C. Molecular Basis of Acute Cystitis Reveals Susceptibility Genes and Immunotherapeutic Targets. PLoS Pathog, 2016 Oct 12, 12(10): e1005848.Ingersoll MA, Kline KA, Nielsen HV, Hultgren SJ. G-CSF induction early in uropathogenic Escherichia coli infection of the urinary tract modulates host immunity. Cell Microbiol, 2008 Dec, 10(12): 2568-78.Ingersoll MA, Kline KA, Nielsen HV, Hultgren SJ. G-CSF induction early in uropathogenic Escherichia coli infection of the urinary tract modulates host immunity. Cell Microbiol, 2008 Dec, 10(12): 2568-78.Hannan TJ, Mysorekar IU, Hung CS, IsaacsonSchmid ML, Hultgren SJ. Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection. PLoS Pathog, 2010 Aug 12 6(8): e1001042.Hannan TJ, Mysorekar IU, Hung CS, IsaacsonSchmid ML, Hultgren SJ. Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection. PLoS Pathog, 2010 Aug 12 6(8): e1001042.Dobrindt U, Wullt B, Svanborg C. Asymtomatic Bacteriuria as a Model to Study the Coevolution of Hosts and Bacteria. Pathogens, 2016 Feb 15, 5(1). pii: E21,Dobrindt U, Wullt B, Svanborg C. Asymtomatic Bacteriuria as a Model to Study the Coevolution of Hosts and Bacteria. Pathogens, 2016 Feb 15, 5(1). pii: E21,Zdziarski J, Brzuszkiewicz E, Wullt B, Liesegang H, Biran D, Voigt B, et al. Host Imprints on Bacterial Genomes-Rapid, Divergent Evolution in Individual Patients. PLoS Pathog, 2010, 6(8).Zdziarski J, Brzuszkiewicz E, Wullt B, Liesegang H, Biran D, Voigt B, et al. Host Imprints on Bacterial Genomes-Rapid, Divergent Evolution in Individual Patients. PLoS Pathog, 2010, 6(8).Lutay N, Ambite I, Gronberg Hernandez J, Rydstrom G, Ragnarsdottir B, Puthia M, Nadeem A, Zhang J, Storm P, Dobrindt U, Wullt B, Svanborg C. Bacterial control of host gene expression through RNA polymerase II. The journal of clinical investigation, 2013, 123(6): 2366-2379.Lutay N, Ambite I, Gronberg Hernandez J, Rydstrom G, Ragnarsdottir B, Puthia M, Nadeem A, Zhang J, Storm P, Dobrindt U, Wullt B, Svanborg C. Bacterial control of host gene expression through RNA polymerase II. The journal of clinical investigation, 2013, 123(6): 2366-2379.Cusumano CK, Pinkner JS, Han Z, Greene SE, Ford BA, Crowley JR, Henderson JP, Janetka JW, Hultgren SJ. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci Transl Med, 2011 Nov 16 3(109): 109ra115.Cusumano CK, Pinkner JS, Han Z, Greene SE, Ford BA, Crowley JR, Henderson JP, Janetka JW, Hultgren SJ. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci Transl Med, 2011 Nov 16 3(109): 109ra115.Beetz R, Westenfelder M. Antimicrobial therapy of urinary tract infections in children. Int J Antimicrob Agents, 2011 Dec, 38(Suppl): 42-50.Beetz R, Westenfelder M. Antimicrobial therapy of urinary tract infections in children. Int J Antimicrob Agents, 2011 Dec, 38(Suppl): 42-50.De Paepe H, Renson C, Van Laecke E, Raes A, Vande Walle J, Hoebeke P. Pelvicfloor therapy and toilet training in young children with dysfunctional voiding and obstipation. BJU Int, 2000, 85: 889–93.De Paepe H, Renson C, Van Laecke E, Raes A, Vande Walle J, Hoebeke P. Pelvicfloor therapy and toilet training in young children with dysfunctional voiding and obstipation. BJU Int, 2000, 85: 889–93.Lettgen B. Prophylaxe rezidivierender Harnwegsinfektionen bei Madchen. Curr Ther Res, 1996, 27: 463–75.Lettgen B. Prophylaxe rezidivierender Harnwegsinfektionen bei Madchen. Curr Ther Res, 1996, 27: 463–75.Zhao J, Wang Z, Chen X, Wang J, Li J. Effects of intravesical liposome-mediated human betadefensin2 gene transfection in a mouseurinary tract infection model. Microbiol Immunol, 2011 Apr, 55(4): 217-23.Zhao J, Wang Z, Chen X, Wang J, Li J. Effects of intravesical liposome-mediated human betadefensin2 gene transfection in a mouseurinary tract infection model. Microbiol Immunol, 2011 Apr, 55(4): 217-23.Lindberg U, Claesson I, Hanson LA, Jodal U. Asymptomatic bacteriuria in schoolgirls. J Pediatr, 1978, 1: 889-893.Lindberg U, Claesson I, Hanson LA, Jodal U. Asymptomatic bacteriuria in schoolgirls. J Pediatr, 1978, 1: 889-893.Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America Guideline for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis, 2005, 40: 643-654.Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America Guideline for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis, 2005, 40: 643-654.Nicolle LE. Asymptomatic bacteriuria: when to screen and when to treat. Infectious Disease Clinics of North America, 2003 Jun, 17(2): 367394.Nicolle LE. Asymptomatic bacteriuria: when to screen and when to treat. Infectious Disease Clinics of North America, 2003 Jun, 17(2): 367394.Brubaker L, Wolfe A. The urinary microbiota: a paradigm shift for bladder disorders? Curr Opin Obstet Gynecol, 2016 Oct, 28(5): 407-12.Brubaker L, Wolfe A. The urinary microbiota: a paradigm shift for bladder disorders? Curr Opin Obstet Gynecol, 2016 Oct, 28(5): 407-12.Nienhouse V, Gao X, Dong Q, Nelson DE, Toh E, McKinley K, Schreckenberger P, Shibata N, Fok CS, Mueller ER, Brubaker L, Wolfe AJ, Radek KA. Interplay between bladder microbiota and urinary antimicrobial peptides: mechanisms for human urinary tract infection risk and symptom severity. PLoS One, 2014, 9(12): e114185.Nienhouse V, Gao X, Dong Q, Nelson DE, Toh E, McKinley K, Schreckenberger P, Shibata N, Fok CS, Mueller ER, Brubaker L, Wolfe AJ, Radek KA. Interplay between bladder microbiota and urinary antimicrobial peptides: mechanisms for human urinary tract infection risk and symptom severity. PLoS One, 2014, 9(12): e114185.

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