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Current Progresses on Vaginal Microbiome, Bacterial Vaginosis and Biofilms

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Current Progresses on Vaginal Microbiome, Bacterial Vaginosis and Biofilms Current progresses on vaginal microbiome, bacterial vaginosis and biofilms Gary Ventolini1, Abdul Hamood2 1 Professor and Regional Dean School of Medicine Texas Tech University Health Sciences Center Permian Basin 800 West, 4th Street. Odessa, Texas, 79705 USA; 2 Professor Department of Immunology and Molecular Microbiology Texas Tech University Health Sciences Center 3601 4th Street. Lub- bock, Texas, 79430 USA. ABSTRACT Recent advances in vaginal microbiome research have indicated that dysbiosis is a complex disorder involving not only cellular and bacterial metabolites, but also hormonal and environmental factors. With newly attained information, harmful gynecological conditions like Bacterial Vaginosis could be efficiently treated to restore health and enhance quality of life across women’s lifespan. Furthermore, newest discoveries on Lactobacilli products and biofilms will let us take care of serious medical conditions. Particularly, relating to antibiotic resistant pathogen biofilm producers like Pseudomonas aeruginosa and benefit patients with severe infected burns and sepsis. We scrutinize the significance of the current progresses on vaginal microbiome, bacterial vaginosis and biofilms. KEYWORDS Vaginal microbiome, bacterial vaginosis, biofilm. Introduction Article history Received 4 May 2020 – Accepted 6 Jun 2020 It is crucial to promote the integration of the available in- Contact formation from the bench (biomedical science with its physi- Gary Ventolini; [email protected] ologic pathways) to bed side (practical clinical application of School of Medicine Texas Tech University Health Sciences Center Permian scientific developments). Basin 800 West, 4th Street. Odessa, Texas, 79705 USA The genital tract microbiome represents 9% of the total women’s microbiome [1]. Recent advances in vaginal microbi- ome research have indicated that dysbiosis is a complex disor- permitted in-depth study of the vaginal microbiome. These der involving not only cellular and bacterial metabolites, but includes DNA fingerprinting, microarrays, quantitative pol- also hormonal and environmental factors. ymerase chain reaction (qPCR), genome sequencing (metagen- With newly acquired knowledge, bothersome and harmful omics), and bacteria specific sequencing 16S ribosome gene. gynecological conditions like Bacterial Vaginosis (BV) could Through these methods we have learned that the human vagina be successfully treated to restore health and enhance quality of is a vastly nutrient-rich cavity for microorganisms (approxi- life across women’s lifespan. mately 200 species has been reported) that bloom into a unique Additionally, newest discoveries on Lactobacilli products complex, dynamic, and diverse microbiome [5]. and biofilms will allow us to address serious medical condi- The vaginal microbiome is under the effect of genetic, ethnic, tions. Predominantly related to pathogen biofilm producers and hormonal, environmental, cultural and behavioral influences. antibiotic resistant microorganisms like Pseudomonas aerugi- This ecosystem in healthy women of childbearing age is habit- nosa which colonizes patients with severe infected burns and ually composed by 4 Lactobacilli that possess a specific vagi- causes fatal sepsis [2]. notropism: L. crispatus, L. jensenii, L. gasseri and L. iners [6]. Vaginotropism is facilitated by pili that act as ligands for at- tachment to glycolipid receptors on vaginal epithelia cells (Fig- Vaginal microbiome ure 1 recognizes the 4 most commonly Lactobacilli found in vagina in circles L. crispatus (blue), L. gasseri (white), L. iners Having a better understanding of the vaginal microbiome (red) and L. jensenii (yellow). It is a wet mount microscopic is required to discern the pathogenesis of several ailments like image in normal saline solution at 200x magnification). Bacterial vaginosis [3]. Lactobacilli are obligate homo-fermenters of glucose from Accordingly, a multicenter epidemiological study started in which they produce lactic acid that helps maintain a stable vag- China to analyze the vaginal microbiome by means of the Vag- inal pH between 3.8 and 4.4. In addition, Lactobacilli produce inal Microecology Evaluation System (VMES) [4]. hydrogen peroxide that allied with host myeloperoxidase and Subsequently, innovative molecular techniques have chloride ions, forms very powerful lethal oxidants that halt 136 Licens terms Gynecological and Reproductive Endocrinology and Metabolism 2020; 1(3):136-140 Progresses on vaginal microbiome, BV, biofilms pathogenic bacteria from flourishing. Hydrogen peroxide also Figure 1 In this we are identifying the 4 most commonly Lactobacilli suppresses G. vaginalis and Mobiluncus. L. Crispatus and L. found in vagina: L. crispatus, L. gasseri, L. iners, L. jensenii. Wet mount microscopic image in normal saline solution at 200x magnification. Jensenii are known to be hydrogen peroxide producers [7]. Other products by Lactobacilli include organic acids, hy- droxy [1] radicals, bio surfactants, arginine deaminases and bi- ofilm. Lactobacilli are likewise known to produce bacteriocins (ribosomal-produced antimicrobial peptides) which likewise defend the vaginal milieu from pathogen bacteria [8]. Bacteriocins induce cell membrane permeabilization, alter- ing ATR amino acids and ion efflux; therefore, transmembrane potential and provoke pH gradient depletion. Lactic acid poten- tiates bacteriocins and hydrogen peroxide. Additionally, Bacteriocins express host cell immunity: NO hemolytic or cytotoxic activity. For instance, Lactocin 160A targets the cyto-membrane of G. vaginalis [9]. Bacterial vaginosis Bacterial Vaginosis (BV) is a vaginal disorder associated to a poly-microbial overgrowth of Gram-negative anaerobes and gram-positives bacteria, that displace most of Lactobacilli ex- cept sometimes L. iners. Historical synopsis It was in 1955, when Gardner and Dukes identified a small for its conciseness in describing the essential of their identified gram negative bacillus in over 90% of women suffering from vaginitis, today’s Bacterial Vaginosis [10] (Figure 2 Shows the vaginitis which was termed Hemophilus vaginalis, since it was typical “Clue Cells”: Bacteria obscuring the borders of vaginal thought that bacterium to be the etiologic agent of this condi- epithelial cells, giving them a stippled appearance. Wet mount tion [10]. In their original research article, Gardner and Dukes microscopic image in normal saline solution at 100x magnifi- also described in patients with this vaginitis, characteristic ep- cation with Gram Stain). ithelial cells that presented distinctive stippled borders appear- A few years later it was found that Hemophilus vagina- ance by being covered with bacteria [10,11]. lis was gram-positive, therefore the microbiologists suggest- Gardner and Dukes called them “Clue cells”, a name chosen ed that should be transferred to the genus Corynebacterium Figure 2 Clue Cells: Bacteria obscuring the borders of vaginal epithelial cells, giving them a stippled appearance. Wet mount microscopic image in normal saline solution at 100x magnification with Gram Stain. Gynecological and Reproductive Endocrinology and Metabolism 2020; 1(3):136-140 137 Ventolini G et al as Corynebacterium vaginalis (CV). Nevertheless, in 1977 is under the influence of sexual hormones although the repro- Greenwood and Pickell informed that CV was both gram-inter- ductive tract leukocytes do not have estrogen or progesterone mediate and unrelated to the previously described Corynebac- receptors [5,15,19]. terium genera. Hereafter they elected to place it in a new ge- The innate immune system recognizes molecular patterns nus, Gardnerella, as Gardnerella vaginalis [12]. associated with pathogens (PAMP). When PAMP is recog- nized, it activates lymphocytes T and B causing pro-inflam- Bacterial vaginosis account matory cytokines release and the start of cellular and humoral BV is a syndrome caused by communities of bacteria that in- immunity. The innate immune system acts rapidly but the ac- clude uncultivated species. BV could be clinically asympto- quired immunity system requires days. matic or be characterized by an increased thin gray or whitish Factors active in the vagina are mannose-binding lectin vaginal discharge, with a foul, fishy like odor. Emotionally (MBL), complement and the membrane-associated compo- could be associated with embarrassment, uneasiness, and dis- nents called Toll-like receptors (TLRs). MBL are antimicrobial tress. There is a rise in vaginal pH from normal to 4.5 and over protein synthesized in the liver. MBL binds to bacterial man- 5.5. Any or several of the more than the 180 species of bacteria nose-containing polysaccharide surfaces activate complement present in the vagina may generate dysbiosis and BV. Especial- and cause bacteriolysis. The vagina also contains Defensins ly when conditions alter, reduce, blocked, or deplete the domi- which are nonspecific antimicrobial activity molecules. More- nant Lactobacilli [13]. over, Secretory Leukocyte Protease Inhibitor (SLPI) destroys The most commonly cultured bacteria in BV include: Gram-positive and Gram-negative bacteria. These proteins are Gardnerella vaginalis, Mycoplasma hominis, Atopobium va- reduced in patients with BV [5,15,19]. ginae, Mobiluncus spp, Bacteroides spp, Clostridiales spp, Vaginal Epithelial Cells (VEC) provide an exclusive mi- Peptostreptococcus spp, Prevotela spp, Fusobacterium, and croenvironment that preserves vaginal health by nurturing en- Porphyromonas spp amongst others [7,14]. dogenous
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