About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Logout
Obstetrics and Gynegology2023№12
Application of fluorescent in situ...

Application of fluorescent in situ hybridization in the diagnosis of bacterial vaginosis

DOI
https://dx.doi.org/10.18565/aig.2023.129

Savicheva A.M., Krysanova A.A., Shalepo K.V., Spasibova E.V., Budilovskaya O.V., Khusnutdinova T.A., Tapilskaya N.I., Kogan I.Yu., Swidsinski A.V., Swidsinski S.

1) D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction, St. Petersburg, Russia; 2) St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, St. Petersburg, Russia; 3) St. Petersburg State University, St. Petersburg, Russia; 4) Molecular-Genetic Laboratory for Polymicrobial Infections and Biofilms, Charit, Hospital, Berlin, Germany; 5) International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms; 6) I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia

Bacterial vaginosis (BV) is a polymicrobial biofilm vaginal syndrome characterized by a high prevalence, recurrence rate and associated complications, including preterm birth, infertility and a higher risk of sexually transmitted infections. Traditional diagnostic methods used to detect the disease do not provide complete information on the morphology, number, and spatial arrangement of microorganisms associated with BV. Fluorescence in situ hybridization (FISH) combines the accuracy of molecular genetics with the informative power of microscopy to visualize the relationships between bacteria in their natural microhabitat, such as the biofilm in BV. The persistence of biofilm composed of BV-associated microorganisms is one of the most likely pathways for recurrence and is an important diagnostic marker for the disease.  The review of the literature presents the history of the use of FISH, outlines its basic principles and demonstrates its advantages in the diagnosis of bacterial vaginosis, especially its recurrent forms.
Conclusion: The use of the FISH method may not only change the understanding of BV pathogenesis, but it can also identify the etiological agent in each particular case, diagnose biofilm/non-biofilm vaginosis by determining the spatial relationship of bacteria to each other and to epithelial cells, predict the recurrence of the disease and choose the appropriate therapy.

Authors’ contributions: Savicheva A.M., Krysanova A.A. – review of publications on the topic of the article, analysis of the data obtained, writing of the manuscript, approval of the final version of the article; Shalepo K.V., Spasibova E.V., Budilovskaya O.V., Khusnutdinova T.A., Tapilskaya N.I., Swidsinski S. – manuscript editing, approval of the final version of the article; Kogan I.Yu.,  Swidsinski A.V. – final manuscript editing and approval of the final version of the article. 
Conflicts of interest: The authors have no conflicts of interest to declare. 
Funding: The study was conducted within the framework of the initiative theme. 
For citation: Savicheva A.M., Krysanova A.A., Shalepo K.V., Spasibova E.V., Budilovskaya O.V., Khusnutdinova T.A., Tapilskaya N.I., Kogan I.Yu., Swidsinski A.V., Swidsinski S. Application of fluorescent in situ hybridization in the diagnosis of bacterial vaginosis. 
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (12): 68-77 (in Russian)
https://dx.doi.org/10.18565/aig.2023.129

Keywords

recurrent bacterial vaginosis recurrent
biofilm
FISH
Gardnerella spp
Full text (in Russian)

References

  1. Redelinghuys M.J., Geldenhuys J., Jung H., Kock M.M. Bacterial vaginosis: Current diagnostic avenues and future opportunities. Front. Cell. Infect. Microbiol. 2020; 10:354. https://dx.doi.org/10.3389/fcimb.2020.00354.
  2. Савичева А.М. Современные представления о лабораторной диагностике репродуктивно значимых инфекций у женщин репродуктивного возраста. Мнение эксперта. Вопросы практической кольпоскопии. Генитальные инфекции. 2022; (3): 34-9. [Savicheva A.M. Modern ideas about the laboratory diagnosis of reproductively significant infections in women of reproductive age. Expert opinion. Issues of Practical Colposcopy & Genital Infections. 2022; (3): 34-9 (in Russian)]. https://dx.doi.org/10.46393/27826392_2022_3_34.
  3. Pandya S., Ravi K., Srinivas V., Jadhav S., Khan A., Arun A. et al. Comparison of culture-dependent and culture-independent molecular methods for characterization of vaginal microflora. J. Med. Microbiol. 2017; 66(2): 149-53. https://dx.doi.org/10.1099/jmm.0.000407.
  4. Свидзинская С., Свидзинский А.В., Савичева А.М., Гущин А.Е. Патогенез бактериального вагинозa: расширяем знания и лечебные возможности. StatusPraesens. Гинекология, акушерство, бесплодный брак. 2023; 3(98): 39-46. [Svidzinskaya S., Svidzinsky A.V., Savicheva A.M., Gushchin A.E. Pathogenesis of bacterial vaginosis: expanding knowledge and therapeutic possibilities. StatusPraesens. Gynecology, obstetrics, infertile marriage. 2023; 3(98): 39-46(in Russian)].
  5. Gall J.G., Pardue M.L. Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc. Natl. Acad. Sci. USA. 1969; 63(2): 378-83. https://dx.doi.org/10.1073/pnas.63.2.378.
  6. John H.A., Birnstiel M.L., Jones K.W. RNA-DNA hybrids at the cytological level. Nature. 1969; 223(5206): 582-7. https://dx.doi.org/10.1038/223582a0.
  7. Giovannoni S.J., DeLong E.F., Olsen G.J., Pace N.R. Phylogenetic group-specific oligodeoxynucleotide probes for identification of single microbial cells. J. Bacteriol. 1988; 170(2): 720-6. https://dx.doi.org/10.1128/jb.170.2.720-726.1988.
  8. McNicol A.M., Farquharson M.A. In situ hybridization and its diagnostic applications in pathology. J. Pathol. 1997; 182(3): 250-61. https://dx.doi.org/10.1002/(SICI)1096-9896(199707)182:3<250::AID-PATH837>3.0.CO;2-S..
  9. Moter A., Göbel U.B. Fluorescence in situ hybridization (FISH) for direct visualization of microorganisms. J. Microbiol. Methods. 2000; 41(2): 85-112. https://dx.doi.org/10.1016/s0167-7012(00)00152-4.
  10. Bauman J.G., Wiegant J., Borst P., van Duijn P. A new method for fluorescence microscopical localization of specific DNA sequences by in situ hybridization of fluorochromelabelled RNA. Exp. Cell. Res. 1980; 128(2): 485-90.https://dx.doi.org/10.1016/0014-4827(80)90087-7.
  11. Amann R., Moraru C. Two decades of fluorescence in situ hybridization in systematic and applied microbiology. Syst. Appl. Microbiol. 2012; 35(8): 483-4. https://dx.doi.org/10.1016/j.syapm.2012.10.002.
  12. Kikhney J., Moter A. Quality control in diagnostic fluorescence in situ hybridization (FISH) in microbiology. Methods Mol. Biol. 2021; 2246: 301-6. https://dx.doi.org/10.1007/978-1-0716-1115-9_20.
  13. Peebles K., Velloza J., Balkus J.E., McClelland R.S., Barnabas R.V. High global burden and costs of bacterial vaginosis: A systematic review and meta-analysis. Sex. Transm. Dis. 2019; 46(5): 304-11. https://dx.doi.org/10.1097/OLQ.0000000000000972.
  14. Ng B.K., Chuah J.N., Cheah F.C., Mohamed Ismail N.A., Tan G.C.,Wong K.K. et al. Maternal and fetal outcomes of pregnant women with bacterial vaginosis. Front. Surg. 2023; 10:1084867. https://dx.doi.org/10.3389/fsurg.2023.1084867.
  15. Martins B.C.T., Guimarães R.A., Alves R.R.F., Saddi V.A. Bacterial vaginosis and cervical human papillomavirus infection in young and adult women: a systematic review and meta-analysis. Rev. Saude Publica. 2023; 56:113.https://dx.doi.org/10.11606/s1518-8787.2022056004412.
  16. Skafte-Holm A., Humaidan P., Bernabeu A., Lledo B., Jensen J.S., Haahr T. The association between vaginal dysbiosis and reproductive outcomes in sub-fertile women undergoing IVF-treatment: A systematic PRISMA review and meta-analysis. Pathogens. 2021; 10(3): 295. https://dx.doi.org/10.3390/pathogens10030295.
  17. Joag V., Obila O., Gajer P., Scott M.C., Dizzell S., Humphrys M. et al. Impact of standard bacterial vaginosis treatment on the genital microbiota, immune milieu, and ex vivo human immunodeficiency virus susceptibility. Clin. Infect. Dis. 2019; 68(10): 1675-83. https://dx.doi.org/10.1093/cid/ciy762.
  18. Abou Chacra L., Fenollar F., Diop K. Bacterial vaginosis: What do we currently know? Front. Cell. Infect. Microbiol. 2022; 11: 672429. https://dx.doi.org/10.3389/fcimb.2021.672429.
  19. Oduyebo O.O., Anorlu R.I., Ogunsola F.T. The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women. Cochrane Database Syst. Rev. 2009; (3): CD006055. https://dx.doi.org/10.1002/14651858.
  20. Zemouri C., Wi T.E., Kiarie J., Seuc A., Mogasale V., Latif A. et al. The performance of the vaginal discharge syndromic management in treating vaginal and cervical infection: A systematic review and meta-analysis. PLoS One. 2016; 11(10):e0163365. https://dx.doi.org/10.1371/journal.pone.0163365.
  21. Bradshaw C.S., Morton A.N., Hocking J., Garland S.M., Morris M.B., Moss L.M. et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J. Infect. Dis. 2006; 193(11): 1478-86. https://dx.doi.org/10.1086/503780.
  22. Bostwick D.G., Woody J., Hunt C., Budd W. Antimicrobial resistance genes and modelling of treatment failure in bacterial vaginosis: clinical study of 289 symptomatic women. J. Med. Microbiol. 2016; 65(5): 377-86.https://dx.doi.org/10.1099/jmm.0.000236.
  23. Faught B.M., Reyes S. Characterization and treatment of recurrent bacterial vaginosis. J. Women’s Health (Larchmt). 2019; 28(9): 1218-26.https://dx.doi.org/10.1089/jwh.2018.7383.
  24. Vodstrcil L.A., Muzny C.A., Plummer E.L., Sobel J.D., Bradshaw C.S. Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment. BMC Med. 2021; 19(1): 194. https://dx.doi.org/10.1186/s12916-021-02077-3.
  25. Moser C., Pedersen H.T., Lerche C.J., Kolpen M., Line L., Thomsen K. et al. Biofilms and host response - helpful or harmful. APMIS. 2017; 125(4): 320-38. https://dx.doi.org/10.1111/apm.12674.
  26. Vestby L.K., Grønseth T., Simm R., Nesse L.L. Bacterial biofilm and its role in the pathogenesis of disease. Antibiotics (Basel). 2020; 9(2): 59.https://dx.doi.org/10.3390/antibiotics9020059.
  27. Muzny C.A., Taylor C.M., Swords W.E., Tamhane A., Chattopadhyay D., Cerca N. et al. An updated conceptual model on the pathogenesis of bacterial vaginosis. J. Infect. Dis. 2019; 220(9): 1399-405. https://dx.doi.org/10.1093/infdis/jiz342.
  28. Machado A., Cerca N. Influence of biofilm formation by Gardnerella vaginalis and other anaerobes on bacterial vaginosis. J. Infect. Dis. 2015; 212(12): 1856-61. https://dx.doi.org/10.1093/infdis/jiv338.
  29. Rosca A.S., Castro J., França Â., Vaneechoutte M., Cerca N. Gardnerella vaginalis dominates multi-species biofilms in both pre-conditioned and competitive in vitro biofilm formation models. Microb. Ecol. 2022; 84(4): 1278-87.https://dx.doi.org/10.1007/s00248-021-01917-2.
  30. Amsel R., Totten P.A., Spiegel C.A., Chen K.C., Eschenbach D., Holmes K.K. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am. J. Med. 1983; 74(1): 14-22. doi: 10.1016/0002-9343(83)91112-9.
  31. Swidsinski A., Mendling W., Loening-Baucke V., Ladhoff A., Swidsinski S.,Hale L.P. et al. Adherent biofilms in bacterial vaginosis. Obstet. Gynecol. 2005; 106(5 Pt 1): 1013-23. https://dx.doi.org/10.1097/01.AOG.0000183594.45524.d2.
  32. Swidsinski A., Loening-Baucke V., Swidsinski S., Sobel J.D., Dörffel Y., Guschin A. Clue cells and pseudo clue cells in different morphotypes of bacterial vaginosis. Front. Cell. Infect. Microbiol. 2022; 12: 905739. https://dx.doi.org/10.3389/fcimb.2022.905739.
  33. Coudray M.S., Madhivanan P. Bacterial vaginosis - a brief synopsis of the literature. Eur. J. Obstet. Gynecol. Reprod. Biol. 2020; 245: 143-8.https://dx.doi.org/10.1016/j.ejogrb.2019.12.035.
  34. Gardner H.L., Dukes C.D. Haemophilus vaginalis vaginitis: a newly defined specific infection previously classified non-specific vaginitis. Am. J. Obstet. Gynecol. 1955; 69(5): 962-76.
  35. Morrill S., Gilbert N.M., Lewis A.L. Gardnerella vaginalis as a cause of bacterial vaginosis: appraisal of the evidence from in vivo models. Front. Cell. Infect. Microbiol. 2020; 10:168. https://dx.doi.org/10.3389/fcimb.2020.00168.
  36. Крысанова А.А., Гущин А.Е., Савичева А.М. Значение определения генотипов Gardnerella vaginalis в диагностике рецидивирующего бактериального вагиноза. Медицинский алфавит. 2021; 1(30): 48-52. [Krysanova A.A., Guschin A.E., Savicheva A.M. Significance of Gardnerella vaginalis genotyping in diagnosis of recurrent bacterial vaginosis. Medical alphabet. 2021; 1(30): 48-52. (in Russian)]. https://dx.doi.org/10.33667/2078-5631-2021-30-48-52.
  37. Castro J., Alves P., Sousa C., Cereija T., França Â., Jefferson K.K. et al. Using an in-vitro biofilm model to assess the virulence potential of bacterial vaginosis or non-bacterial vaginosis Gardnerella vaginalis isolates. Sci. Rep. 2015; 5: 11640. https://dx.doi.org/10.1038/srep11640.
  38. Alves P., Castro J., Sousa C., Cereija T.B., Cerca N. Gardnerella vaginalis outcompetes 29 other bacterial species isolated from patients with bacterial vaginosis, using in an in vitro biofilm formation model. J. Infect. Dis. 2014; 210(4): 593-6. https://dx.doi.org/10.1093/infdis/jiu131.
  39. Castro J., Machado D., Cerca N. Unveiling the role of Gardnerella vaginalis in polymicrobial bacterial vaginosis biofilms: the impact of other vaginal pathogens living as neighbors. ISME J. 2019; 13(5): 1306-17. https://dx.doi.org/10.1038/s41396-018-0337-0.
  40. Swidsinski A., Doerffel Y., Loening-Baucke V., Swidsinski S., Verstraelen H.,Vaneechoutte M. et al. Gardnerella biofilm involves females and males and is transmitted sexually. Gynecol. Obstet. Invest. 2010; 70(4): 256-63.https://dx.doi.org/10.1159/000314015.
  41. Vaneechoutte M., Guschin A., Van Simaey L., Gansemans Y., Van Nieuwerburgh F., Cools P. Emended description of Gardnerella vaginalis and description of Gardnerella leopoldii sp. nov., Gardnerella piotii sp. nov. and Gardnerella swidsinskii sp. nov., with delineation of 13 genomic species within the genus Gardnerella. Int. J. Syst. Evol. Microbiol. 2019; 69(3): 679-87.https://dx.doi.org/10.1099/ijsem.0.003200.
  42. Swidsinski A., Loening-Baucke V., Mendling W., Dörffel Y., Schilling J.,Halwani Z. et al. Infection through structured polymicrobial Gardnerella biofilms (StPM-GB). Histol. Histopathol. 2014; 29(5): 567-87.https://dx.doi.org/10.14670/HH-29.10.567.

Received 22.05.2023

Accepted 20.09.2023

About the Authors

Alevtina M. Savicheva, Dr. Med. Sci., Professor, Head of the Department of Medical Microbiology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russiua, St. Petersburg, Mendeleevskaya line, 3; Head of the Department of Clinical Laboratory Diagnostics, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, 194100, Russia, St. Petersburg, Litovskaya str., 2; Head of the International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms, savitcheva@mail.ru, https://orcid.org/0000-0003-3870-5930
Anna A. Krysanova, PhD, MD, Researcher, Experimental Microbiology Group, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia,
St. Petersburg, Mendeleyevskaya line, 3; Assistant, Department of Clinical Laboratory Diagnostics, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, 194100, Russia, St. Petersburg, Litovskaya str., 2; PhD, MD, Researcher, International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms, krusanova.anna@mail.ru, https://orcid.org/0000-0003-4798-1881
Kira V. Shalepo, PhD, MD, Senior Researcher, Experimental Microbiology Group, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology,
199034, St. Petersburg, Mendeleevskaya line, 3; Associate Professor, Department of Clinical Laboratory Diagnostics of AF and DPO, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, 194100, Russia, St. Petersburg, Litovskaya str., 2; PhD, MD, Senior Researcher, International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms, 2474151@mail.ru, https://orcid.org/0000-0002-3002-3874
Elena V. Spasibova, bacteriologist, Laboratory of Clinical Microbiology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, St. Petersburg, Mendeleyevskaya line, 3; Assistant, Department of Clinical Laboratory Diagnostics, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, 194100, Russia, St. Petersburg, Litovskaya str., 2; bacteriologist, International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms, elena.graciosae@gmail.com, https://orcid.org/0009-0002-6070-4651
Olga V. Budilovskaya, PhD, MD, Senior Researcher, Experimental Microbiology Group, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology,
199034, Russia, St. Petersburg, Mendeleevskaya line, 3; Assistant, Department of Clinical Laboratory Diagnostics of AF and DPO, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, 194100, Russia, St. Petersburg, Litovskaya str., 2; PhD, MD, Senior Researcher, International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms, o.budilovskaya@gmail.com, https://orcid.org/0000-0001-7673-6274
Tatiana A. Khusnutdinova, PhD, MD, Senior Researcher, Experimental Microbiology Group, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, St. Petersburg, Mendeleyevskaya line, 3; Assistant, Department of Clinical Laboratory Diagnostics, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, 194100, Russia, St. Petersburg, Litovskaya str., 2; PhD, MD, Senior Researcher, International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms, husnutdinovat@yandex.ru, https://orcid.org/0000-0002-2742-2655
Natalya I. Tapilskaya, Dr. Med. Sci., Professor, Leading Researcher of the Reproduction Department, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, St. Petersburg, Mendeleevskaya line, 3; Professor, Department of Obstetrics and Ginecology, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, 194100, Russia, St. Petersburg, Litovskaya str., 2, tapnatalia@ yandex.ru, https://orcid.org/0000-0001-5309-0087
Igor Yu. Kogan, Corresponding Member of the RAS, Dr. Med. Sci., Professor, Director, D.O. Ott Reasearch Institute of Obstetrics, Gynecology and Reproductology,
199034, Russia, St. Petersburg, Mendeleyevskaya line, 3; Professor, St. Petersburg State University, St. Petersburg, Russia, ovr@ott.ru, https://orcid.org/0000-0002-7351-6900
Alexander V. Swidsinski, Head of the Molecular-Genetic Laboratory for Polymicrobial Infections and Biofilms, Charité CCM, Medizinische Klinik, Universitätsmedizin,
10117 Berlin, Germany; Co-Head of the International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms,
alexander.swidsinski@charite.de, https://orcid.org/0000-0002-7071-0417
Sonia Swidsinski, bacteriologist of the Molecular-Genetic Laboratory for Polymicrobial Infections and Biofilms, Charité CCM, Medizinische Klinik, Universitätsmedizin,
10117 Berlin, Germany; bacteriologist of the International Center for the Study of the Vitality and Resistance of Polymicrobial Communities and Biofilms,
alexander.swidsinski@charite.de
Corresponding author: Anna A. Krysanova, krusanova.anna@mail.ru
By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.