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Pathogens
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Vaginal Bacteria from the Genus Gardnerella
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Vaginal Bacteria from the Genus Gardnerella

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (20 May 2021) | Viewed by 35596

Special Issue Editor

Dr. Milda Pleckaityte

E-Mail Website
Guest Editor
Institute of Biotechnology, Life Sciences Center, Vilnius University, 10257 Vilnius, Lithuania
Interests: human vaginal microbiota; bacteria Gardnerella; cholesterol-dependent cytolysins; bacterial virulence

Special Issue Information

Dear Colleagues,

More than 60 years have passed since the description of the vaginitis-related bacterium Haemophilus vaginalis by Gardner and Dukes [1]. The later studies reclassified this bacterium into Gardnerella vaginalis, the only species in the genus Gardnerella. For a long time, Gardnerella remained the bacterial vaginosis-associated bacterium, which potentially has a pivotal role in the pathogenesis of anaerobic dysbiosis is conditioned by specific virulence factors [2]. Indeed, a biofilm predominantly formed by Gardnerella on vaginal epithelial cells became a hallmark of bacterial vaginosis [3]. Sialidase activity of Gardnerella is associated with mucus degradation and presumably inactivation of host sialylated immune mediators, like immunoglobulins IgA [4,5]. The cytotoxic activity of cholesterol-dependent cytolysin, vaginolysin, secreted by Gardnerella is potentially linked with vaginal epithelial cell desquamation detected in bacterial vaginosis-positive women [6,7]. However, Gardnerella is often found in the vagina of asymptomatic women having Lactobacillus-dominated vaginal microbiota. There are likely differences in virulence among Gardnerella strains that condition their pathogenic or nonpathogenic activity. Moreover, the expression of virulence traits in different Gardnerella species may be diversely affected under certain conditions that promote their specific roles in vaginal microbiota [8]. A recent study identified and described 13 new species within the genus Gardnerella, including Gardnerella leopoldii, Gardnerella swidsinskii, Gardnerella piotii, and Gardnerella vaginalis [9]. The question of how to correctly differentiate these new species remains of high importance. It becomes clear that knowledge of G. vaginalis accumulated to date needs to be reviewed in the light of taxonomic assignments that reflect genetic heterogeneity within the genus Gardnerella.

This Special Issue aims to gain scientific knowledge of the emended species G. vaginalis and the newly described G. swidsinskii, G. piotii, and G. leopoldii. In this issue, we also seek to characterize Gardnerella isolates, which are not attributed to the species described. We invite articles on Gardnerella species differentiation, species physiology and metabolism, epidemiology, phenotypic and genotypic characteristics, virulence factors, susceptibility to antibiotics, interaction with the host, microbial interactions, role in vaginal microbiota, and case reports. The list of topics is not exhaustive, and other related topics are open for consideration. Research papers, reviews, and short reports will be considered for publication. We look forward to your contribution.

References:

  1. Gardner HL and Dukes CD. Haemophilus vaginalis vaginitis: a newly defined specific infection previously classified non-specific vaginitis. Am. J. Obstet. Gynecol. 1955; 69: 962–976.
  2. Muzny C A and Schwebke J R. Gardnerella vaginalis: Still a prime suspect in the pathogenesis of bacterial vaginosis. Curr. Infect. Dis. Rep. 2013; 15, 130–135. doi:10.1007/s11908-013-0318-4.
  3. Swidsinski, A., Loening-Baucke, V., Mendling, W., Dörffel, Y., Schilling, J., Halwani, Z., et al. Infection through structured polymicrobial Gardnerella biofilms (StPM-GB). Histol. Histophatol. 2014; 29, 567–587.
  4. Cauci S, Culhane JF, Di Santolo M, McCollum K. Among pregnant women with bacterial vaginosis, the hydrolytic enzymes sialidase and prolidase are positively associated with interleukin-1beta. J. Obstet. Gynecol. 2008; 198(1):132.e1-7.
  5. Lewis WG, Robinson LS, Gilbert NM, Perry JC, Lewis AL. Degradation, foraging, and depletion of mucus sialoglycans by the vagina-adapted Actinobacterium Gardnerella vaginalis. J. Biol. Chem. 2013; 288:12067-79. doi: 10.1074/jbc.M113.453654
  6. Gelber SE, Aguilar JL, Lewis KLT, Ratner A J. Functional and phylogenetic characterization of vaginolysin, the human-specific cytolysin from Gardnerella vaginalis. J. Bacteriol. 2008; 190: 3896–3903. doi:10.1128/JB.01965-07.
  7. 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: 1306–1317. doi:10.1038/s41396-018-0337-0.
  8. Castro J, Jefferson KK, Cerca N. Genetic heterogeneity and taxonomic diversity among Gardnerella Trends Microbiol. 2019; pii: S0966-842X(19)30257-4. doi: 10.1016/j.tim.2019.10.002.
  9. Vaneechoutte M, Guschin A, Van Simaey L, Gansemans Y, Van Nieuwerburgh F, Cool, P. Emended description of Gardnerella vaginalis and description of Gardnerella leopoldii sp. nov., Gardnerella piotii nov. and Gardnerella swidsinskii sp. nov., with delineation of 13 genomic species within the genus Gardnerella. Int. J. Syst. Evol. Microbiol. 2019; 69:679–687. doi:10.1099/ijsem.0.003200.

Dr. Milda Pleckaityte
Guest Editor

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Keywords

  • Gardnerella
  • vaginal microbiota
  • bacterial vaginosis, virulence factors

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Published Papers (7 papers)

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Research

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9 pages, 1189 KiB  
Article
Discrimination of Gardnerella Species by Combining MALDI-TOF Protein Profile, Chaperonin cpn60 Sequences, and Phenotypic Characteristics
by Aistė Bulavaitė, Thomas Maier and Milda Pleckaityte
Pathogens 2021, 10(3), 277; https://doi.org/10.3390/pathogens10030277 - 1 Mar 2021
Cited by 2 | Viewed by 2432
Abstract
The description of Gardnerella vaginalis was recently updated and three new species, including nine genome species within Gardnerella, were defined using whole genome sequences and matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. A fast and simple method based [...] Read more.
The description of Gardnerella vaginalis was recently updated and three new species, including nine genome species within Gardnerella, were defined using whole genome sequences and matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. A fast and simple method based on readily available techniques would be of immense use to identify Gardnerella species in research and clinical practice. Here we show that 34 previously characterized Gardnerella isolates were assigned to the species using partial chaperonin cpn60 sequences. The MALDI Biotyper from Bruker Daltonik GmbH demonstrated the capability to differentiate the phylogenetically diverse groups composed of G. vaginalis/G. piotii and G. leopoldii/G. swidsinskii. Among the phenotypic properties that characterize Gardnerella species are sialidase and β-galactosidase activities. Our data confirmed that the NanH3 enzyme is responsible for sialidase activity in Gardnerella spp. isolates. Almost all G. piotii isolates displayed a sialidase positive phenotype, whereas the majority of G. vaginalis strains were sialidase negative. G. leopoldii and G. swidskinskii displayed a sialidase negative phenotype. β-galactosidase is produced exclusively in G. vaginalis strains. Earlier determined phenotypic characteristics associated with virulence of Gardnerella isolates now assigned to the defined species may provide insights on how diverse species contribute to shaping the vaginal microbiome. Full article
(This article belongs to the Special Issue Vaginal Bacteria from the Genus Gardnerella)
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11 pages, 3575 KiB  
Article
Dequalinium Chloride Effectively Disrupts Bacterial Vaginosis (BV) Gardnerella spp. Biofilms
by Carlos Gaspar, Joana Rolo, Nuno Cerca, Rita Palmeira-de-Oliveira, José Martinez-de-Oliveira and Ana Palmeira-de-Oliveira
Pathogens 2021, 10(3), 261; https://doi.org/10.3390/pathogens10030261 - 25 Feb 2021
Cited by 20 | Viewed by 4345
Abstract
Bacterial vaginosis (BV) is the most frequent vaginal infection worldwide. It is caused by the overgrowth of anaerobic vaginal pathogens such as Gardnerella spp. BV has been associated with the occurrence of dense multispecies biofilms on the vaginal mucosa. Treatment of biofilm-associated infections [...] Read more.
Bacterial vaginosis (BV) is the most frequent vaginal infection worldwide. It is caused by the overgrowth of anaerobic vaginal pathogens such as Gardnerella spp. BV has been associated with the occurrence of dense multispecies biofilms on the vaginal mucosa. Treatment of biofilm-associated infections such as BV is challenging. In this study, we have tested the role of a quaternary ammonium compound, dequalinium chloride (DQC), in the eradication of Gardnerella spp. biofilms. The effects of the test substance on the biomass and the metabolic activity of the biofilm of Gardnerella spp. were assessed in vitro using a microtiter plate assay. In addition, the effect of DQC on the Gardnerella spp. biofilm was further assessed by using scanning electron microscopy and confocal laser scanning microscopy. The results showed that DQC was particularly effective in the destruction of BV-associated Gardnerella spp. biotypes, impacting both their biomass and metabolic activity. In addition, the disruption of biofilm architecture was evident and was probably caused by multiple mechanisms of action. We conclude that DQC is an antibiofilm agent and is able to efficiently destroy Gardnerella spp. BV-associated biofilms. Therefore, it is a valid option for BV therapy and has the potential to prevent BV recurrences. Full article
(This article belongs to the Special Issue Vaginal Bacteria from the Genus Gardnerella)
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15 pages, 2498 KiB  
Article
Atopobium vaginae and Prevotella bivia Are Able to Incorporate and Influence Gene Expression in a Pre-Formed Gardnerella vaginalis Biofilm
by Joana Castro, Aliona S. Rosca, Christina A. Muzny and Nuno Cerca
Pathogens 2021, 10(2), 247; https://doi.org/10.3390/pathogens10020247 - 20 Feb 2021
Cited by 33 | Viewed by 8715
Abstract
Bacterial vaginosis (BV) is associated with a highly structured polymicrobial biofilm on the vaginal epithelium where Gardnerella species presumably play a pivotal role. Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia are vaginal pathogens detected during the early stages of incident BV. [...] Read more.
Bacterial vaginosis (BV) is associated with a highly structured polymicrobial biofilm on the vaginal epithelium where Gardnerella species presumably play a pivotal role. Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia are vaginal pathogens detected during the early stages of incident BV. Herein, we aimed to analyze the impact of A. vaginae and P. bivia on a pre-established G. vaginalis biofilm using a novel in vitro triple-species biofilm model. Total biofilm biomass was determined by the crystal violet method. We also discriminated the bacterial populations in the biofilm and in its planktonic fraction by using PNA FISH. We further analyzed the influence of A. vaginae and P. bivia on the expression of key virulence genes of G. vaginalis by quantitative PCR. In our tested conditions, A. vaginae and P. bivia were able to incorporate into pre-established G. vaginalis biofilms but did not induce an increase in total biofilm biomass, when compared with 48-h G. vaginalis biofilms. However, they were able to significantly influence the expression of HMPREF0424_0821, a gene suggested to be associated with biofilm maintenance in G. vaginalis. This study suggests that microbial relationships between co-infecting bacteria can deeply affect the G. vaginalis biofilm, a crucial marker of BV. Full article
(This article belongs to the Special Issue Vaginal Bacteria from the Genus Gardnerella)
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8 pages, 845 KiB  
Communication
Vaginal, Cervical and Uterine pH in Women with Normal and Abnormal Vaginal Microbiota
by Malene Risager Lykke, Naja Becher, Thor Haahr, Ebbe Boedtkjer, Jørgen Skov Jensen and Niels Uldbjerg
Pathogens 2021, 10(2), 90; https://doi.org/10.3390/pathogens10020090 - 20 Jan 2021
Cited by 23 | Viewed by 4657
Abstract
Introduction: Healthy women of reproductive age have a vaginal pH around 4.5, whereas little is known about pH in the upper genital tract. A shift in the vaginal microbiota may result in an elevated pH in the upper genital tract. This might contribute [...] Read more.
Introduction: Healthy women of reproductive age have a vaginal pH around 4.5, whereas little is known about pH in the upper genital tract. A shift in the vaginal microbiota may result in an elevated pH in the upper genital tract. This might contribute to decreased fertility and increased risk of preterm birth. Therefore, we aimed to measure pH in different compartments of the female genital tract in both nonpregnant and pregnant women, stratifying into a normal and abnormal vaginal microbiota. Material and methods: In this descriptive study, we included 6 nonpregnant, 12 early-pregnant, and 8 term-pregnant women. A pH gradient was recorded with a flexible pH probe. An abnormal vaginal microbiota was diagnosed by a quantitative polymerase chain reaction technique for Atopobium vaginae; Sneathia sanguinegens; Leptotrichia amnionii; bacterial vaginosis-associated bacterium 1, 2, 3, and TM7; and Prevotella spp. among others. Results: In all participants we found the pH gradient in the lower reproductive canal to be most acidic in the lower vagina and most alkaline in the upper uterine cavity. Women with an abnormal vaginal microbiota had an increased pH in the lower vagina compared to the other groups. Conclusions: There is a pronounced pH gradient within the female genital tract. This gradient is not disrupted in women with an abnormal vaginal microbiota. Full article
(This article belongs to the Special Issue Vaginal Bacteria from the Genus Gardnerella)
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15 pages, 14021 KiB  
Article
Sequence Comparison of Vaginolysin from Different Gardnerella Species
by Erin M. Garcia, Myrna G. Serrano, Laahirie Edupuganti, David J. Edwards, Gregory A. Buck and Kimberly K. Jefferson
Pathogens 2021, 10(2), 86; https://doi.org/10.3390/pathogens10020086 - 20 Jan 2021
Cited by 13 | Viewed by 3473
Abstract
Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may [...] Read more.
Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may be one factor that distinguishes less virulent or commensal strains from more virulent strains. This was assessed by bioinformatic analyses of publicly available Gardnerella spp. sequences and quantification of cytotoxicity and cytokine production from purified, recombinantly produced versions of VLY. After identifying conserved differences that could distinguish distinct VLY types, we analyzed metagenomic data from a cohort of female subjects from the Vaginal Human Microbiome Project to investigate whether these different VLY types exhibited any significant associations with symptoms or Gardnerella spp.-relative abundance in vaginal swab samples. While Type 1 VLY was most prevalent among the subjects and may be associated with increased reports of symptoms, subjects with Type 2 VLY dominant profiles exhibited increased relative Gardnerella spp. abundance. Our findings suggest that amino acid differences alter the interaction of VLY with vaginal keratinocytes, which may potentiate differences in bacterial vaginosis (BV) immunopathology in vivo. Full article
(This article belongs to the Special Issue Vaginal Bacteria from the Genus Gardnerella)
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18 pages, 3664 KiB  
Article
Type II Restriction-Modification System from Gardnerella vaginalis ATCC 14018
by Aistė Bulavaitė, Indre Dalgediene, Vilma Michailoviene and Milda Pleckaityte
Pathogens 2020, 9(9), 703; https://doi.org/10.3390/pathogens9090703 - 27 Aug 2020
Cited by 2 | Viewed by 3508
Abstract
Intensive horizontal gene transfer may generate diversity and heterogeneity within the genus Gardnerella. Restriction-modification (R-M) systems and CRISPR-Cas are the principal defense tools against foreign DNA in bacteria. Nearly half of the tested Gardnerella spp. isolates harbored the CRISPR-Cas system. Several putative [...] Read more.
Intensive horizontal gene transfer may generate diversity and heterogeneity within the genus Gardnerella. Restriction-modification (R-M) systems and CRISPR-Cas are the principal defense tools against foreign DNA in bacteria. Nearly half of the tested Gardnerella spp. isolates harbored the CRISPR-Cas system. Several putative R-M systems of Gardnerella spp. strains were identified in the REBASE database. However, there was no experimental evidence for restriction endonuclease (REase) activity in the isolates. We showed that G. vaginalis strain ATCC 14018 contains the REase R.Gva14018I, which recognizes GGCC and most probably generates blunt ends on cleavage. Bioinformatics evidence and the activity of recombinant methyltransferase M.Gva14018I in vivo indicate that ATCC 14018 possesses a HaeIII-like R-M system. The truncated R.Gva14018I-4 lacking the C-terminal region was expressed in Escherichia coli and displayed wild-type REase specificity. Polyclonal antibodies against R.Gva14018I-4 detected the wild-type REase in the cell lysate of ATCC 14018. The cofactor requirements for activity and bioinformatics analysis indicated that R.Gva14018I belongs to the PD-(D/E)XK family of REases. The REase-like activity was observed in 5 of 31 tested Gardnerella spp. strains, although none of these matched the DNA digestion pattern of R.Gva14018I. Full article
(This article belongs to the Special Issue Vaginal Bacteria from the Genus Gardnerella)
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Review

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17 pages, 417 KiB  
Review
The Association between Vaginal Dysbiosis and Reproductive Outcomes in Sub-Fertile Women Undergoing IVF-Treatment: A Systematic PRISMA Review and Meta-Analysis
by Axel Skafte-Holm, Peter Humaidan, Andrea Bernabeu, Belen Lledo, Jørgen Skov Jensen and Thor Haahr
Pathogens 2021, 10(3), 295; https://doi.org/10.3390/pathogens10030295 - 4 Mar 2021
Cited by 26 | Viewed by 4777
Abstract
Recent advances in molecular microbiology have enabled refined studies of the genital tract microbiota. This constitutes the basis of the present updated systematic review and meta-analysis which investigate vaginal dysbiosis (VD) as defined by either microscopy (e.g., Nugent score for bacterial vaginosis) or [...] Read more.
Recent advances in molecular microbiology have enabled refined studies of the genital tract microbiota. This constitutes the basis of the present updated systematic review and meta-analysis which investigate vaginal dysbiosis (VD) as defined by either microscopy (e.g., Nugent score for bacterial vaginosis) or molecular methods (qPCR and Next Generation Sequencing) to evaluate the impact of VD on the reproductive outcomes in women undergoing IVF-treatment. A total of 17 studies were included, comprising 3543 patients and with a VD prevalence of 18% (95%CI 17–19). Across all methods, VD is a significant risk factor for early pregnancy loss in IVF (Relative risk (RR) = 1.71 95%CI 1.29–2.27). Moreover, a predefined sub-analysis of studies using molecular methods for VD diagnosis showed a significant reduction in the clinical pregnancy rate when compared to normal vaginal microbiota patients (RR = 0.55 95%CI 0.32–0.93). However, regardless of diagnostic methodology, VD did not significantly influence live birth rate (LBR). In conclusion, molecular tools have provided a more detailed insight into the vaginal microbiota, which may be the reason for the increased adverse effect estimates in IVF patients with molecularly defined VD. However, the quality of evidence was very low across all outcomes according to GRADE and thus, more studies are warranted to understand the impact of VD in IVF. Full article
(This article belongs to the Special Issue Vaginal Bacteria from the Genus Gardnerella)
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