scholarly journals Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lenka A. Vodstrcil ◽  
Christina A. Muzny ◽  
Erica L. Plummer ◽  
Jack D. Sobel ◽  
Catriona S. Bradshaw
Keyword(s):  
Bacterial Vaginosis ◽  
Vaginal Microbiome ◽  
Epidemiological Evidence ◽  
Associated Bacteria ◽  
Sexually Transmitted ◽  
Single Mechanism ◽  
Challenges And Opportunities ◽  
Key Driver ◽  
Barriers And Challenges ◽  
High Level

AbstractBacterial vaginosis (BV) is the most common vaginal dysbiosis to affect women globally, yet an unacceptably high proportion of women experience BV recurrence within 6 months of recommended antibiotic therapy. The low rate of sustained cure highlights our limited understanding of the pathogenesis of BV recurrence, which has been attributed to possible persistence and re-emergence of BV-associated bacteria (BVAB) or a BV-associated biofilm following antimicrobials and/or reinfection occurring from sexual partners.There is a robust body of evidence to support the exchange of bacteria between partners during sexual activity, and while the hypothesis that women treated for BV are subsequently reinfected with BVAB following sex with an untreated sexual partner is not new, failure of past partner treatment trials has eroded confidence in this concept. If reinfection is a key driver of recurrence, current antimicrobial regimens directed to women alone are unlikely to achieve a high level of sustained cure, and the approach of partner treatment to reduce reinfection is justified. In this manuscript, we present the molecular and epidemiological evidence that underlies the hypothesis that BV is sexually transmitted, and summarise why research that continues to consider sexual partnerships is necessary. We also outline the significant barriers and challenges that we have identified while undertaking partner treatment studies, and we discuss the factors that impact on our ability to determine their effectiveness.Ultimately, the pathogenesis of BV recurrence is likely to be multifaceted and not attributable to a single mechanism in all women. If we are to achieve sustained cure for women, it is likely that combined and individualised approaches to eradicate BVAB, support an optimal vaginal microbiome, and prevent reinfection from partners will be required.

scholarly journals Two Novel Vaginal Microbicides (Polystyrene Sulfonate and Cellulose Sulfate) Inhibit Gardnerella vaginalis and Anaerobes Commonly Associated with Bacterial Vaginosis

2002 ◽  
Vol 46 (8) ◽  
pp. 2692-2695 ◽  
Author(s):  
Jose A. Simoes ◽  
Diane M. Citron ◽  
Alla Aroutcheva ◽  
Robert A. Anderson ◽  
Calvin J. Chany ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Gardnerella Vaginalis ◽  
Polystyrene Sulfonate ◽  
Cellulose Sulfate ◽  
Transmitted Infection ◽  
Vaginal Microbicides ◽  
Associated Bacteria ◽  
Sexually Transmitted ◽  
Immunodeficiency Virus

ABSTRACT This is the first report demonstrating the in vitro inhibitory activity of two novel microbicides (cellulose sulfate and polystyrene sulfonate) against bacterial vaginosis (BV)-associated bacteria. Vaginal application of these microbicides not only may reduce the risk of acquisition of human immunodeficiency virus and other sexually transmitted infection-causing organisms but may also decrease the incidence of BV.

scholarly journals Characterization of an α-glucosidase enzyme conserved in Gardnerella spp. isolated from the human vaginal microbiome

2021 ◽  
Author(s):  
Pashupati Bhandari ◽  
Jeffrey P. Tingley ◽  
David R. J. Palmer ◽  
D. Wade Abbott ◽  
Janet E. Hill
Keyword(s):  
Microbial Community ◽  
Bacterial Vaginosis ◽  
Glycogen Metabolism ◽  
Maximum Activity ◽  
Glycoside Hydrolase Family ◽  
Vaginal Microbiome ◽  
Sexually Transmitted ◽  
Multistep Process ◽  
Mixed Bacteria

Gardnerella spp. in the vaginal microbiome are associated with bacterial vaginosis, in which a lactobacilli dominant community is replaced with mixed bacteria including Gardnerella species. Co-occurrence of multiple Gardnerella species in the vaginal environment is common, but different species are dominant in different women. Competition for nutrients, including glycogen, could play an important role in determining the microbial community structure. Digestion of glycogen into products that can be taken up and further processed by bacteria requires the combined activities of several enzymes collectively known as amylases, which belong to glycoside hydrolase family 13 (GH13) within the CAZy classification system. GH13 is a large and diverse family of proteins, making prediction of their activities challenging. SACCHARIS annotation of the GH13 family in Gardnerella resulted in identification of protein domains belonging to eight subfamilies. Phylogenetic analysis of predicted amylase sequences from 26 genomes demonstrated that a putative α-glucosidase-encoding sequence, CG400_06090, was conserved in all Gardnerella spp. The predicted α-glucosidase enzyme was expressed, purified and functionally characterized. The enzyme was active on a variety of maltooligosaccharides with maximum activity at pH 7. K m , k cat and k cat /K m values for the substrate 4-nitrophenyl α- d -glucopyranoside were 8.3 μM, 0.96 min −1 and 0.11 μM −1 min −1 , respectively. Glucose was released from maltose, maltotriose, maltotetraose and maltopentaose, but no products were detected when the enzyme was incubated with glycogen. Our findings show that Gardnerella spp. produce an α-glucosidase enzyme that may contribute to the multistep process of glycogen metabolism by releasing glucose from maltooligosaccharides. IMPORTANCE Increased abundance of Gardnerella spp. is a diagnostic characteristic of bacterial vaginosis, an imbalance in the human vaginal microbiome associated with troubling symptoms, and negative reproductive health outcomes including increased transmission of sexually transmitted infections and preterm birth. Competition for nutrients is likely an important factor in causing dramatic shifts in the vaginal microbial community but little is known about the contribution of bacterial enzymes to the metabolism of glycogen, a major carbon source available to vaginal bacteria. The significance of our research is characterizing the activity of an enzyme conserved in Gardnerella species that likely contributes to the ability of these bacteria to utilize glycogen.

scholarly journals The Female Vaginal Microbiome in Health and Bacterial Vaginosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaodi Chen ◽  
Yune Lu ◽  
Tao Chen ◽  
Rongguo Li
Keyword(s):  
Bacterial Vaginosis ◽  
Therapeutic Strategies ◽  
Reproductive Age ◽  
Gardnerella Vaginalis ◽  
Obstetric Outcomes ◽  
Antimicrobial Compounds ◽  
Vaginal Microbiome ◽  
Sharp Decline ◽  
Women Of Reproductive Age ◽  
Sexually Transmitted

The vaginal microbiome is an intricate and dynamic microecosystem that constantly undergoes fluctuations during the female menstrual cycle and the woman’s entire life. A healthy vaginal microbiome is dominated by Lactobacillus which produce various antimicrobial compounds. Bacterial vaginosis (BV) is characterized by the loss or sharp decline in the total number of Lactobacillus and a corresponding marked increase in the concentration of anaerobic microbes. BV is a highly prevalent disorder of the vaginal microbiota among women of reproductive age globally. BV is confirmed to be associated with adverse gynecologic and obstetric outcomes, such as sexually transmitted infections, pelvic inflammatory disease, and preterm birth. Gardnerella vaginalis is the most common microorganism identified from BV. It is the predominant microbe in polymicrobial biofilms that could shelter G. vaginalis and other BV-associated microbes from adverse host environments. Many efforts have been made to increase our understanding of the vaginal microbiome in health and BV. Thus, improved novel and accurate diagnosis and therapeutic strategies for BV have been developed. This review covers the features of vaginal microbiome, BV, BV-associated diseases, and various strategies of diagnosis and treatment of BV, with an emphasis on recent research progresses.

scholarly journals Longitudinal profiling of the macaque vaginal microbiome reveals similarities to diverse human vaginal communities: implications for use as a pre-clinical model for bacterial vaginosis

2020 ◽  
Author(s):  
Nicholas S Rhoades ◽  
Sara M Hendrickson ◽  
Danielle R Gerken ◽  
Kassandra Martinez ◽  
Ov D Slayden ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Rhesus Macaque ◽  
Rhesus Macaques ◽  
Adverse Outcomes ◽  
Reproductive Age ◽  
Lactobacillus Species ◽  
Vaginal Microbiome ◽  
Clinical Model ◽  
Sexually Transmitted ◽  
Increased Susceptibility

The vaginal microbiota plays an important role in women's reproductive and urogenital health. Disturbances in this microbial community can lead to several adverse outcomes including pelvic inflammatory disease, bacterial vaginosis (BV) as well as increased susceptibility to sexually transmitted infections, miscarriage, and pre-term births. It is now well accepted that while the microbiome of healthy women in the developed world is dominated by Lactobacillus species, vaginal communities in asymptomatic women, especially those in the developing world, can be comprised of a diverse set of micro-organisms. The presence of a diverse vaginal microbiome has been associated with increased susceptibility to HIV infection but their implications for women's health remain poorly understood. Rhesus macaques are an excellent translational animal model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive age female rhesus macaques. Many animals showed hallmarks of BV, including Nugent scores above 7 and high vaginal pH. At both the taxonomic and functional level, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic gram-negative bacteria, including; Snethia, Prevotella, Porphyromonas, and Mobilluncus. Interestingly, some animals were transiently colonized by Lactobacillus and some with Gardnerella. Our in-depth and comprehensive analysis highlights the importance of the model to test interventions for manipulating the vaginal microbiome.

scholarly journals The Effect of Oral Metronidazole on the Vaginal Microbiome of Patients with Recurrent Bacterial Vaginosis: A Pilot Investigational Study

2021 ◽  
pp. 100081
Author(s):  
Oluwatosin Goje ◽  
Elizabeth O. Shay ◽  
Metabel Markwei ◽  
Roshan Padmanabhan ◽  
Charis Eng
Keyword(s):  
Bacterial Vaginosis ◽  
Vaginal Microbiome ◽  
Oral Metronidazole

scholarly journals Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 54
Author(s):  
Christine Landlinger ◽  
Lenka Tisakova ◽  
Vera Oberbauer ◽  
Timo Schwebs ◽  
Abbas Muhammad ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Bactericidal Activity ◽  
High Selectivity ◽  
Ex Vivo ◽  
Vaginal Microbiome ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Promising Alternative ◽  
First Time

Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13–8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.

Bacterial Vaginosis-Associated Bacteria and Uterine Fibroids

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Kristen R. Moore ◽  
Meena Tomar ◽  
David M. Umbach ◽  
Scott E. Gygax ◽  
David W. Hilbert ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Uterine Fibroids ◽  
Associated Bacteria
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