Cerca, Nuno

Guschin, Alexander

Swidsinski, Alexander

Vaneechoutte, Mario

Research in Microbiology

Nuno Cerca

Mario Vaneechoutte

Alexander Guschin

Alexander Swidsinski

Crossref

Polymicrobial infections and biofilms in women's health

Ghent University Academic Bibliography

Polymicrobial infections and biofilms in women's health : Gahro Expert Group meeting report

Universidade do Minho: RepositoriUM

Research in Microbiology 168 (2017) 902e904www.elsevier.com/locate/resmicMeeting reporthttp://d0923-2Polymicrobial infections and biofilms in women's healthGahro Expert Group Meeting Report1. In the beginning …The conference took place between the 11th and 14th ofMay 2017 in the medieval village of Gahro, near Berlin. It wasorganized by the Molecular Genetics Laboratory for Poly-microbial Infections and Biofilms, Charite, Universit€atsmedizinBerlin. Scientists representing 11 European centers involved inresearch on the vaginal microbiome came together to exchangetheir opinion over present and future frontiers of research.2. Is bacterial vaginosis lost in translation?A key objective of this meeting was to address the multi-disciplinary recent developments highlighting the role ofmulti-species biofilms in the etiology of bacterial vaginosis(BV). Throughout the meeting, a recurrent question wasasked: When we describe BV, are we talking about the samething? In other words, are there different types of BV? Or arewe using the term BV for a different set of etiological con-ditions with similar symptoms? Per Goran Larsson (Depart-ment of Obstetrics and Gynecology, Link€oping UniversityHospital, 581 85 Link€oping, Sweden) argued that BV researchis now on the rise, but despite the hundreds of yearly pub-lications, there are still a lot of controversial studies that arenot helping to unravel BV etiology.Traditionally, vaginal dysbiosis includes Candida vaginitis[1] Trichomonas vaginitis [2] and BV [3], but as GilbertDonders (Department of Obstetrics & Gynecology AntwerpUniversity, Antwerp, Belgium) points out, other significantdysbioses are being neglected and can account for significantconsequences for women's health. Donders argued that aerobicvaginitis (AV) or BV mixed flora could be more predictive ofpreterm labor than BV [4]. A major problem with differ-entiation between BV and other dysbioses is the lack of properdiagnostic methods, since neither the classical Nugent score northe Amsel criteria provide very reliable results (sensitivity andspecificity often below 90%) [5], nor do they add understandingto the pathogenesis of disease, which is purely descriptive.Furthermore, Mario Vaneechoutte pointed out the possi-bility of the existence of different triggers for development ofBV, with the possibility of spontaneous and transientx.doi.org/10.1016/j.resmic.2017.07.002508/© 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rightsphysiological BV [6] and a sexually transmittable, persistentBV [7], by means of fragments of biofilms consisting ofGardnerella and other species [8].The confusion of attitudes is probably unavoidable as longas everybody understands something different about BV.Working with clearly defined entities like Gardnerellosis(defined as Gardnerella conditioned polymicrobial biofilmdisease) would be more helpful. FISH is highly efficient in thedirect visualization of polymicrobial BV biofilms and theircomponents, but requires skilled staff, is not available every-where and is probably over-used for clinical purposes. Thecommercially available multiplex qPCR tests based on esti-mation of the ratio between concentrations of Lactobacillusspp DNA and Gardnerella vaginalis and Atopobium vaginaeare quick, reliable, adequate and meet clinical needs. Otherdiagnostic methods are in progress. Simon Cameron (ImperialCollege London, Charing Cross Hospital, London, UK) pre-sented data on in situ ionization mass spectrometry, whichoffers a scope of new possibilities to visualize and investigatemetabolomics of microbiota directly in human tissues.3. Microbiome diversity and diversity of bacterial speciesNovel deep sequencing studies have improved our under-standing of the vaginal microbiome [9,10]. However, thesestudies fail to provide functional or mechanistic evidence tosupport a direct causeeeffect link [11]. In fact, as pointed outby Nuno Cerca, among the few direct functional studiesaddressing virulent traits of BV-associated bacteria, often G.vaginalis stands out as the most promising virulent candidate[12,13]. Elena Spasibova (D.O. Ott Research Institute ofObstetrics, Gynecology and Reproductology Mendeleevskayaline, 3, St. Petersburg, Russia) presented data on the diversityof vaginal lactobacilli in healthy women and pointed out thatthe composition of the vaginal biotope is an indicator of awoman's reproductive health, with significant differencesbetween the lactobacilli population usually found in healthyand BV women [14].A closely related issue is whether BV exists withoutG. vaginalis and whether health can co-exist with G. vaginalis.Most of the sequence_based investigations demonstrate thatreserved.903Meeting report / Research in Microbiology 168 (2017) 902e904Gardnerella is obligatorily present in BV. However, dependingon the definition criteria of dysbiosis and diagnostic methodsused, some investigators claim the possibility of Gardner-ella_negative BV [10,15]. On the other hand, its co-occurrencein health does not necessarily indicate the inoffensiveness andregular distribution within a normal population, but morelikely the requirement for additional factors for Gardnerella toexpress pathogenicity. G. vaginalis is a common component ofthe vaginal microbiota. It is much more abundant in womenwith bacterial vaginosis [16]. The phenotypic heterogeneity ofG. vaginalis is well known, and several biotyping and geno-typing methods have been developed [17,18]. Recent genomicanalysis has revealed four G. vaginalis genome groups, withgreat differences between each other [19].Kira Shalepo (D.O. Ott Research Institute of Obstetrics,Gynecology and Reproductology Mendeleevskaya line, 3, St.Petersburg, Russia), in collaboration with Alexander Guschin'sgroup, followed up on the discussion by presenting detaileddata on the diversity and prevalence of the different G. vagi-nalis genotypes in healthy and BV women. Since G. vaginalisis known to establish synergistic relationships with otherbacterial species, Guschin proposed that different G. vaginalisgenotypes could interact synergistically and be responsible forthe development of BV.4. The polymicrobial biofilm hypothesisAn important milestone in BV research was the discoverythat the different species involved in BV were associated in astructured polymicrobial biofilm, dominated by G. vaginalisand often including A. vaginae and several lactobacilli spp.[20]. Alexander Swidsinski argued that to understand poly-microbial cultures, we have to investigate them as a structure-functional unity. Swidsinski proposed that BV biofilms containcore organisms, which are necessary for propagation, highlyspecialized for this task, and disabled for autonomic growthoutside of the consolidated polymicrobial biofilm. He arguedthat Gardnerella-driven biofilms may be a transitional stateand the missing link in evolution from isolated living pro-karyotes to completely interdependent polymicrobial com-munities, giving rise to eukaryotes. It is unclear whichparticipants in the polymicrobial BV biofilm belong to theessential core of the biofilm, which are individual symbiontsor accidental beneficiaries. Besides various Gardnerella gen-otypes, the most interesting participants seem to be A. vaginae,Lactobacillus iners and Mycoplasma.5. Taking home a messageBV is not just amorphous dysbiosis, but rather, a number ofdifferent diseases which still have to be precisely definedbased on pathogenic rather than descriptive criteria and usingproper diagnostic methods. New sequencing and functionaldata seem to suggest that Gardnerella is not uniform.The future may reveal that some of the known genotypesare, in fact, distinct species. Furthermore, it is now evident thatlactobacilli are not totally beneficial. Some may be involved inpathogenesis of dysbiosis and adverse pregnancy outcome.This seems to be evident, at least in the case of L. iners. Strongdata indicate that L. iners and AV might be even more stronglyassociated with preterm birth than BV.Conflict of interestThe authors have no conflict of interest to declare.References[1] Donders GGG, Sobel JD. Candida vulvovaginitis: a store with a butteryand a show window. Mycoses 2017;60:70e2.[2] Kissinger P. Trichomonas vaginalis: a review of epidemiologic, clinicaland treatment issues. BMC Infect Dis 2015;15:307.[3] Nasioudis D, Linhares I, Ledger W, Witkin S. Bacterial vaginosis: acritical analysis of current knowledge. BJOG Int J Obstet Gynaecol2017;124:61e9.[4] Donders GGG, Bellen G, Grinceviciene S, Ruban K, Vieira-Baptista P.Aerobic vaginitis: no longer a stranger. Res Microbiol 2017;168:845e58.[5] Africa CW. Efficacy of methods used for the diagnosis of bacterialvaginosis. Expert Opin Med Diagn 2013;7:189e200.[6] Leppaluoto PA. Bacterial vaginosis: what is physiological in vaginalbacteriology? An update and opinion. Acta Obstet Gynecol Scand2011;90:1302e6.[7] Schwebke JR, Muzny CA, Josey WE. Role of Gardnerella vaginalis inthe pathogenesis of bacterial vaginosis: a conceptual model. J Infect Dis2014;210:338e43.[8] Swidsinski A, Loening-Baucke V, Mendling W, D€orffel Y, Schilling J,Halwani Z, et al. Infection through structured polymicrobial Gardnerellabiofilms (StPM-GB). Histol Histopathol 2014;29:567e87.[9] Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SSK, McCulle SL, et al.Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U SA 2011;108:4680e7.[10] Srinivasan S, Hoffman NG, Morgan MT, Matsen FA, Fiedler TL,Hall RW, et al. Bacterial communities in women with bacterial vaginosis:high resolution phylogenetic analyses reveal relationships of microbiotato clinical criteria. PLoS ONE 2012;7:e37818.[11] Onderdonk AB, Delaney ML, Fichorova RN. The human microbiomeduring bacterial vaginosis. Clin Microbiol Rev 2016;29:223e38.[12] Alves P, Castro J, Sousa C, Cereija TB, Cerca N. Gardnerella vaginalisoutcompetes 29 other bacterial species isolated from patients with bac-terial vaginosis, using in an in vitro biofilm formation model. J Infect Dis2014:210.[13] Patterson JL, Stull-Lane A, Girerd PH, Jefferson KK. Analysis ofadherence, biofilm formation and cytotoxicity suggests a greater viru-lence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes. Microbiology 2010;156:392e9.[14] Petrova MI, Lievens E, Malik S, Imholz N, Lebeer S. Lactobacillusspecies as biomarkers and agents that can promote various aspects ofvaginal health. Front Physiol 2015;6:81.[15] Aroutcheva AA, Simoes JA, Behbakht K, Faro S. Gardnerella vaginalisisolated from patients with bacterial vaginosis and from patients withhealthy vaginal ecosystems. Clin Infect Dis 2001;33:1022e7.[16] Verhelst R, Verstraelen H, Claeys G, Verschraegen G, Delanghe J, VanSimaey L, et al. Cloning of 16S rRNA genes amplified from normal anddisturbed vaginal microflora suggests a strong association between Ato-pobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMCMicrobiol 2004;4:16.[17] Piot P, Van Dyck E, Peeters M, Hale J, Totten PA, Holmes KK. Biotypesof Gardnerella vaginalis. J Clin Microbiol 1984;20:677e9.[18] Ingianni A, Petruzzelli S, Morandotti G, Pompei R. Genotypic differ-entiation of Gardnerella vaginalis by amplified ribosomal DNArestriction analysis (ARDRA). FEMS Immunol Med Microbiol1997;18:61e6.904 Meeting report / Research in Microbiology 168 (2017) 902e904[19] Ahmed A, Earl J, Retchless A, Hillier SL, Rabe LK, Cherpes TL, et al.Comparative genomic analyses of 17 clinical isolates of Gardnerellavaginalis provide evidence of multiple genetically isolated clades con-sistent with subspeciation into genovars. J Bacteriol 2012;194:3922e37.[20] Swidsinski A, Mendling W, Loening-Baucke V, Ladhoff A,Swidsinski S, Hale LP, et al. Adherent biofilms in bacterial vaginosis.Obstet Gynecol 2005;106:1013e23.Nuno Cerca*Center of Biological Engineering, LIBRO, Laboratory ofResearch in Biofilms Rosario Oliveira, University of Minho,Campus de Gualtar, 4710-057 Braga, PortugalMario VaneechoutteLaboratory of Bacteriology Research, Department of ClinicalChemistry, Microbiology & Immunology, Faculty of Medicine& Health Sciences, University of Ghent, Ghent, BelgiumAlexander GuschinRussian Research Center for Molecular Diagnostics andTherapy, Laboratory of Molecular Diagnostics, CentralResearch Institute, Moscow 111123, RussiaAlexander SwidsinskiMolecular Genetics Laboratory for Polymicrobial Infectionsand Biofilms, CCM, Charite, Universit€atsmedizin Berlin,Hufelandweg 5, 10117 Berlin, Germany*Corresponding author.E-mail address: nunocerca@ceb.uminho.pt (N. Cerca).20 June 2017Available online 14 July 2017

Polymicrobial infections and biofilms in women's health Gahro Expert Group Meeting Report

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Polymicrobial infections and biofilms in women's health Gahro Expert Group Meeting Report

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