Ureaplasma diversum Genome Provides New Insights about the Interaction of the Surface Molecules of This Bacterium with the Host

Abstract

Whole genome sequencing and analyses of Ureaplasma diversum ATCC 49782 was undertaken as a step towards understanding U. diversum biology and pathogenicity. The complete genome showed 973,501 bp in a single circular chromosome, with 28.2% of G+C content. A total of 782 coding DNA sequences (CDSs), and 6 rRNA and 32 tRNA genes were predicted and annotated. The metabolic pathways are identical to other human ureaplasmas, including the production of ATP via hydrolysis of the urea. Genes related to pathogenicity, such as urease, phospholipase, hemolysin, and a Mycoplasma Ig binding protein (MIB)—Mycoplasma Ig protease (MIP) system were identified. More interestingly, a large number of genes (n = 40) encoding surface molecules were annotated in the genome (lipoproteins, multiple-banded antigen like protein, membrane nuclease lipoprotein and variable surface antigens lipoprotein). In addition, a gene encoding glycosyltransferase was also found. This enzyme has been associated with the production of capsule in mycoplasmas and ureaplasma. We then sought to detect the presence of a capsule in this organism. A polysaccharide capsule from 11 to 17 nm of U. diversum was observed trough electron microscopy and using specific dyes. This structure contained arabinose, xylose, mannose, galactose and glucose. In order to understand the inflammatory response against these surface molecules, we evaluated the response of murine macrophages J774 against viable and non-viable U. diversum. As with viable bacteria, non-viable bacteria were capable of promoting a significant inflammatory response by activation of Toll like receptor 2 (TLR2), indicating that surface molecules are important for the activation of inflammatory response. Furthermore, a cascade of genes related to the inflammasome pathway of macrophages was also up-regulated during infection with viable organisms when compared to non-infected cells. In conclusion, U. diversum has a typical ureaplasma genome and metabolism, and its surface molecules, including the identified capsular material, represent major components of the organism immunopathogenesis.

Inflammasome activation during spontaneous preterm labor with intra‐amniotic infection or sterile intra‐amniotic inflammation

“…lipopolysacchride) induce the activation of caspase-1 and release of IL-1β in the chorioamniotic membranes 35, 37, 117 and that Ureaplasma species (genital mycoplasmas are the most common microorganisms found in women with IAI 12, 16, 118–123 ) are capable of activating the inflammasome pathway in murine macrophages. 124 Together, these findings indicate that the inflammasome is involved in the mechanisms that lead to microbial-associated preterm labor and birth.…”

“…These results are consistent with previous studies, which demonstrated that amniotic fluid concentrations of caspase-1 33 (the predominant inflammasomeactivated caspase 46 ), IL-1β, 26 and IL-18 106 35,37,117 and that Ureaplasma species (genital mycoplasmas are the most common microorganisms found in women with IAI 12,16,[118][119][120][121][122][123] ) are capable of activating the inflammasome pathway in murine macrophages. 124 Together, these findings indicate that the inflammasome is involved in the mechanisms that lead to microbialassociated preterm labor and birth.…”

Clinical chorioamnionitis at term IX: in vivo evidence of intra-amniotic inflammasome activation

“…ASC/caspase-1 complexes), compared to those without this placental lesion [53,54]. Furthermore, genital mycoplasmas, the most common microorganisms found in women with clinical chorioamnionitis at term and intra-amniotic infection [40,85,108], are capable of activating the inflammasome pathway in murine macrophages [109]. Together, these findings indicate that the inflammasome is involved in the mechanisms that lead to microbial-associated intra-amniotic inflammation in women with clinical chorioamnionitis at term.…”

Ureaplasma diversum and Its Membrane-Associated Lipoproteins Activate Inflammatory Genes Through the NF-κB Pathway via Toll-Like Receptor 4

“…NF-κB and AP-1 regulate important genes associated with inflammation in infection processes ( Garcia et al, 1998 ; Rawadi et al, 1999 ). Accordingly, the recent genome analyses of U. diversum revealed a large number of genes encoding membrane-associated lipoproteins, as well as urease, hemolysin, phospholipase and glycosyltransferase (associated with capsule synthesis) enzymes ( Marques et al, 2015 , 2016 ). These lipoproteins, however, have never been separately analyzed for their host immune system stimulation.…”