Polymicrobial infections and bacterial vaginosis: past, present and future

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Abstract

The studies of the spatial relationships of microorganisms using ribosomal fluorescence in situ hybridization (FISH) suggest that there are many infections caused by groups of functionally cooperating pathogens that only become infectious when transported and grown together.

The research into the interspecies relationships of the vaginal microbiome shows that bacterial vaginosis (BV) is not a single disease, but a complex syndrome involving completely different infectious processes with similar symptoms.

The most common cause of BV syndrome is polymicrobial biofilms (namely biofilm-associated gardnerellosis) followed by cohesive vaginosis mainly caused by Lactobacillus iners. The BV syndrome also includes different types of dysbiosis that have not yet been clearly characterized in terms of composition and causes. It is also possible that they will subsequently break down into specific nosological units depending on the communities (polymicrobial consortia) that cause or prevent their development.

Gardnerella spp. form the bulk of vaginal biofilms in BV, they cooperate with other microorganisms embedded in the biofilm and significantly expand its capacity. Due to interspecies cooperation, biofilm shows high resistance to immunity, antibiotics and hygiene products. Since the combined qualities of polymicrobial communities are absent in the individual species that make up the biofilm, their isolated spread from a sick person to a healthy person is unable to lead to biofilm formation in a new location and cause a disease.

Currently, pathogenic consortia can only be detected using the ribosomal FISH method. Although multiplex PCR or sequencing methods are extremely sensitive, none of them can be useful as they focus only on the detection of individual bacterial species and not on the elucidation of their interspecies relationships. Since stable interspecies interactions depend on specific genes required for the cohesion of the microorganisms involved, the identification of these genes and their use in clinical diagnosis and therapy is a matter of time and challenge for infectious disease specialists.

Conclusion: This review critically examines the contradictions and weaknesses of modern infectious disease studies that aim to identify a single pathogen; it also suggests ways to overcome previous impasses. Many of the problems presented in this article are in the initial stages of development and have yet to be specified, evolved and implemented. Therefore, the above is not a complete doctrine, but rather the collective opinion of obstetricians and gynecologists who are experts in the field and have co-authored and signed a series of tasks for initial implementation in the near future.

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About the authors

Alexander V. Svidsinski

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia; Humboldt University of Berlin

Author for correspondence.
Email: alexander.swidsinski@charite.de

Professor, Department of General Hygiene, Institute of Public Health named after F.F. Erisman, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia; Chief Physician of the Gastroenterological Outpatient Clinic, Head of the Molecular Genetic Laboratory, Humboldt University of Berlin

Russian Federation, Moscow; Berlin, Germany

Sonja V. Svidsinski

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Professor, Department of General Hygiene, Institute of Public Health named after F.F. Erisman

Russian Federation, Moscow

Inna A. Apolikhina

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia; Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Ministry of Health of Russia; Professor, Department of Obstetrics, Gynecology, Perinatology and Reproductology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia; Dr. Med. Sci., Professor, Head of the Department of Aesthetic Gynecology and Rehabilitation, Professor at the Department of Obstetrics and Gynecology, Department of Vocational Education, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology

Russian Federation, Moscow; Moscow

Igor I. Baranov

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Head of the Department of Scientific and Educational Programs, Academician V.I. Kulakov National Medical Research Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Vice President of RSOG

Russian Federation, Moscow

Nadezhda V. Bashmakova

Ural Research Institute for the Protection of Maternity and Infancy, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Honored Doctor of the Russian Federation, Professor, Chief Obstetrician-Gynecologist of the Ural Federal District, Chief Researcher and Head of the Department of Assisted Reproductive Technologies, Urals Scientific Research Institute for Maternal and Child Care, Ministry of Health of Russia

Russian Federation, Yekaterinburg

Lyudmila V. Borovkova

Privolzhsky Research Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, Volga Research Medical University, Ministry of Health of Russia; Chairman of the Nizhny Novgorod branch of the RSOG

Russian Federation, Nizhny Novgorod

Emma P. Gribova

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: gribova_e_p@staff.sechenov.ru

PhD, Chief Physician, Sechenov Center for Motherhood and Childhood, Clinical Center

Russian Federation, Moscow

Mikhail A. Gomberg

Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology, Moscow Healthcare Department

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Chief Researcher, Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology, Moscow City Health Department; Member of the Royal College of Physicians (RCP), Member of the American Academy of Dermatology (AAD), Member of the European Academy of Dermatovenereology (EADV), Senior Advisor to the International Union for Sexually Transmitted Infections (IUSTI)

Russian Federation, Moscow

Alexander E. Gushchin

Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology, Moscow Healthcare Department

Email: alegus65@mail.ru

PhD (Bio)

Russian Federation, Moscow

Tea A. Dzhibladze

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Department of Obstetrics and Gynecology No. 1, Sklifosovsky Institute of Clinical Medicine

Russian Federation, Moscow

Yulia E. Dobrokhotova

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Honored Doctor of the Russian Federation, Honored Scientist of the Russian Federation, Laureate of the Prize of the Government of the Russian Federation, Head of the Department of Obstetrics and Gynecology, Pirogov Russian National Research Medical University, Ministry of Health of Russia

Russian Federation, Moscow

Nina V. Zarochentseva

Academician V.I. Krasnopolsky Moscow Regional Research Institute of Obstetrics and Gynecology; V.F. Vladimirskiy Moscow Regional Research Clinical Institute

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor of the Russian Academy of Sciences, Deputy Director for Research, Academician V.I. Krasnopolsky Moscow Regional Research Institute of Obstetrics and Gynecology; Professor, Department of Obstetrics and Gynecology, V.F. Vladimirsky Moscow Regional Research Clinical Institute

Russian Federation, Moscow; Moscow

Vladimir M. Zuev

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Department of Obstetrics and Gynecology No. 1, Sklifosovsky Institute of Clinical Medicine

Russian Federation, Moscow

Dmitry G. Kim

Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology, Moscow Healthcare Department

Email: alexander.swidsinski@charite.de

PhD, Dermatovenerologist, Head of the Competence Center for Viral Skin Diseases

Russian Federation, Moscow

Ekaterina A. Kostina

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Laboratory for the Diagnosis of Polymicrobial Infections and Bacterial Biofilms

Russian Federation, Moscow

Irina I. Kukarskaya

Tyumen State Medical University, Ministry of Health of Russia; Perinatal Medical Center

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Head of the Department of Obstetrics, Gynecology and Perinatology of the Institute of Motherhood and Childhood, Tyumen State Medical University, Ministry of Health of Russia; Chief Obstetrician-Gynecologist of the Tyumen Region Health Department; Chief Physician, Regional Perinatal Center

Russian Federation, Tyumen; Tyumen

Galina A. Lazareva

Kursk State Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, Institute of Continuing Education

Russian Federation, Kursk

Antonina V. Ledina

Lapino Clinical Hospital of Mother and Child Group

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., co-director of the All-Russian educational project «ZhenProSvet – AGO»; Doctor, Lapino Clinical Hospital of Mother and Child Group

Russian Federation, Moscow Region

Natalia V. Mingaleva

Kuban State Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Department of Obstetrics, Gynecology and Perinatology No. 2, Institute of Continuing Education

Russian Federation, Krasnodar

Galina N. Minkina

Russian University of Medicine, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Department of Obstetrics, Gynecology and Reproductive Medicine

Russian Federation, Moscow

Tatyana V. Priputnevich

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Corresponding Member of RAS, Dr. Med. Sci., Associate Professor, Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Professor, Department of Microbiology and Virology, Faculty of Pediatrics, Pirogov Russian National Research Medical University, Ministry of Health of Russia

Russian Federation, Moscow; Moscow

Alevtina M. Savicheva

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction; St. Petersburg State Pediatric Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Honored Scientist of the Russian Federation, Head of the Department of Medical Microbiology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology; Head of the Department of Medical Microbiology and Clinical Laboratory Diagnostics, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia

Russian Federation, St. Petersburg; St. Petersburg

Margarita V. Semenova

Izhevsk State Medical Academy, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

PhD, Associate Professor, Head of the Department of Obstetrics and Gynecology

Russian Federation, Izhevsk

Nadezhda V. Svidsinski

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Laboratory for the Diagnosis of Polymicrobial Infections and Bacterial Biofilms

Russian Federation, Moscow

Sergey P. Sinchikhin

Astrakhan State Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Medicine

Russian Federation, Astrakhan

Ksenia V. Storozheva

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Email: alexander.swidsinski@charite.de

Obstetrician-Gynecologist, PhD Student at the Department of Reproductology

Russian Federation, St. Petersburg

Gennady T. Sukhikh

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Academician of the RAS, Professor, Dr. Med. Sci., Director

Russian Federation, Moscow

Natalya I. Tapilskaya

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction; St. Petersburg State Pediatric Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Head of the Department of Reproductology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology; Professor, Department of Obstetrics and Gynecology, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia

Russian Federation, St. Petersburg; St. Petersburg

Liana A. Tarnaeva

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Obstetrician-Gynecologist, PhD Student

Russian Federation, Moscow

Alexander L. Tikhomirov

Russian University of Medicine, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Honored Doctor of the Russian Federation, Laureate of the Prize of the Government of the Russian Federation, Professor at the Department of Obstetrics and Gynecology, Russian University of Medicine, Ministry of Health of Russia

Russian Federation, Moscow

Natalya S. Trifonova

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: trifonova.nataly@mail.ru

Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology No. 1 of the N.V. Sklifosovsky ICM, obstetrician-gynecologist at the Sechenov Center for Motherhood and Childhood of the Clinical Center

Russian Federation, Moscow

Ildar F. Fatkullin

Kazan State Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Professor at the Department of Obstetrics and Gynecology, Kazan State Medical University, Ministry of Health of Russia; Chief Freelance Specialist in Obstetrics and Gynecology of the Ministry of Health of Russia in the Volga Federal District

Russian Federation, Kazan

Larisa S. Fatkullina

Kazan State Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

PhD, Associate Professor at the Department of Obstetrics and Gynecology named after Prof. V.S. Gruzdev, Kazan State Medical University, Ministry of Health of Russia; Chief Freelance Obstetrician-Gynecologist of the Kazan Health Department of the Ministry of Health of the Republic of Tatarstan

Russian Federation, Kazan

Alexey A. Khryanin

Novosibirsk State Medical University, Ministry of Health of Russia

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Department of Dermatovenereology and Cosmetology

Russian Federation, Novosibirsk

Nadezhda I. Chernova

Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology, Moscow Healthcare Department

Email: alexander.swidsinski@charite.de

Dr. Med. Sci., Professor, Head of the Department of Anogenital Dermatoses and Sexually Transmitted Infections, Dermatovenerologist

Russian Federation, Moscow

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2. Fig. 1. RiGinaM using Gardnerella 664 Cy5 probe (red fluorescence) and LAB Cy3 probe (all lactobacilli, yellow fluorescence). A1-4 - no adherent bacteria on the surface of vaginal biopsy from healthy women; BV1-BV2 - the vaginal surface of women with BV is covered with a thick biofilm tightly adjoining the epithelium; BV2 - the adhesiveness of the Gardnerella biofilm allows other microorganisms to come into close contact with the vaginal epithelium (BV1 - additional hybridization identified these bacteria as Lactobacillus iners)

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3. Fig. 2. Formation of a key cell when it is separated from the vaginal surface (Gard 664 Cy5 probe)

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4. Fig. 3. Clue cell covered with Cardnerella spp. in urine sediments from a woman and a man (Gard 664 Cy5 probe)

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5. Fig. 4. Smear from a woman with BV without biofilm. Lactobacillus iners (L. iners Cy3 probe) forms cohesive islands-flakes (Sludge), not adhered to epithelial cells. The latter are clearly visible due to the blue staining of DAPI. The situation is typical for pseudo clue cells.

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