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Clinical Microbiology Reviews Jan 2006Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of... (Review)
Review
Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health.
Topics: Amino Acid Sequence; Bacterial Outer Membrane Proteins; Humans; Molecular Sequence Data; Sequence Alignment; Syphilis; Treponema pallidum
PubMed: 16418521
DOI: 10.1128/CMR.19.1.29-49.2006 -
Clinical Microbiology Reviews Jan 2014The agents of human treponematoses include four closely related members of the genus Treponema: three subspecies of Treponema pallidum plus Treponema carateum. T.... (Review)
Review
The agents of human treponematoses include four closely related members of the genus Treponema: three subspecies of Treponema pallidum plus Treponema carateum. T. pallidum subsp. pallidum causes venereal syphilis, while T. pallidum subsp. pertenue, T. pallidum subsp. endemicum, and T. carateum are the agents of the endemic treponematoses yaws, bejel (or endemic syphilis), and pinta, respectively. All human treponematoses share remarkable similarities in pathogenesis and clinical manifestations, consistent with the high genetic and antigenic relatedness of their etiological agents. Distinctive features have been identified in terms of age of acquisition, most common mode of transmission, and capacity for invasion of the central nervous system and fetus, although the accuracy of these purported differences is debated among investigators and no biological basis for these differences has been identified to date. In 2012, the World Health Organization (WHO) officially set a goal for yaws eradication by 2020. This challenging but potentially feasible endeavor is favored by the adoption of oral azithromycin for mass treatment and the currently focused distribution of yaws and endemic treponematoses and has revived global interest in these fascinating diseases and their causative agents.
Topics: Animals; Disease Eradication; Disease Models, Animal; Endemic Diseases; Treponema; Treponemal Infections
PubMed: 24396138
DOI: 10.1128/CMR.00070-13 -
Microbiology Spectrum Oct 2021More than 75 species/species-level phylotypes belonging to the genus Treponema inhabit the human oral cavity. Treponema denticola is commonly associated with periodontal...
More than 75 species/species-level phylotypes belonging to the genus Treponema inhabit the human oral cavity. Treponema denticola is commonly associated with periodontal disease, but the etiological roles and ecological distributions of other oral treponemes remain more obscure. Here, we compared the clinical distributions of phylogroup 1 and 2 oral treponemes in subgingival plaque sampled from Chinese subjects with periodontitis ( = 10) and gingivitis ( = 8) via sequence analysis of the highly conserved housekeeping gene. Two PCR primer sets that targeted oral phylogroup 1 and 2 treponeme genes were used to construct plasmid clone amplicon libraries for each subject, and the libraries were sequenced for bioinformatic analysis. A total of 1,204 quality-filtered, full-length gene sequences were obtained from the cohort (median number, 61.5 cloned sequences per subject; range, 59 to 83), which were assigned to 34 genotypes (designated pyrH001 to pyrH034; 97% sequence identity cutoff). Eighteen genotypes (536 sequences) corresponded to phylogroup 1 treponeme taxa (including Treponema vincentii and Treponema medium). Sixteen genotypes (668 sequences) corresponded to T. denticola and other phylogroup 2 treponemes. Samples from periodontitis subjects contained a greater diversity of phylogroup 2 genotypes than did samples from gingivitis subjects (Mann-Whitney U test). One T. denticola genotype (pyrH001) was highly prevalent, detected in 10/10 periodontitis and 6/8 gingivitis subjects. Several subjects harbored multiple T. denticola genotypes. Nonmetric multidimensional scaling and permutational multivariate analysis of variance (PERMANOVA) revealed no significant differences in overall genotype compositions between periodontitis and gingivitis subjects. Taken together, our results show that subjects with periodontitis and gingivitis commonly harbor highly taxonomically diverse communities of oral treponemes. Periodontal diseases, such as periodontitis, are highly complex, multifactorial inflammatory infectious diseases affecting the gums and tooth-supporting structures. They are caused by chronic accumulations of dental plaque below the gum line that typically comprise hundreds of different bacterial species. Certain species of spiral-shaped bacteria known as treponemes, most notably Treponema denticola, are proposed to play key roles in the development and progression of periodontal disease. In our study, we characterized the genetic lineages of T. denticola, Treponema vincentii, Treponema medium, and related species of treponeme bacteria that were present in dental plaque samples from Chinese subjects with periodontal disease. Our results revealed that individual subjects commonly harbored multiple genetic lineages (strains) of T. denticola and other species of treponeme bacteria. Taken together, our results indicate that highly diverse and complex populations of oral treponemes may be present in dental plaque, which may potentially play important roles affecting periodontal health status.
Topics: Cohort Studies; Gingivitis; Microbiota; Mouth; Periodontal Diseases; Periodontitis; Phylogeny; Polymerase Chain Reaction; RNA, Ribosomal, 16S; Species Specificity; Treponema; Treponema denticola; Treponemal Infections
PubMed: 34585987
DOI: 10.1128/Spectrum.00701-21 -
Current Topics in Microbiology and... 2018The outer membrane (OM) of Treponema pallidum, the uncultivatable agent of venereal syphilis, has long been the subject of misconceptions and controversy. Decades ago,... (Review)
Review
The outer membrane (OM) of Treponema pallidum, the uncultivatable agent of venereal syphilis, has long been the subject of misconceptions and controversy. Decades ago, researchers postulated that T. pallidum's poor surface antigenicity is the basis for its ability to cause persistent infection, but they mistakenly attributed this enigmatic property to the presence of a protective outer coat of serum proteins and mucopolysaccharides. Subsequent studies revealed that the OM is the barrier to antibody binding, that it contains a paucity of integral membrane proteins, and that the preponderance of the spirochete's immunogenic lipoproteins is periplasmic. Since the advent of recombinant DNA technology, the fragility of the OM, its low protein content, and the lack of sequence relatedness between T. pallidum and Gram-negative outer membrane proteins (OMPs) have complicated efforts to characterize molecules residing at the host-pathogen interface. We have overcome these hurdles using the genomic sequence in concert with computational tools to identify proteins predicted to form β-barrels, the hallmark conformation of OMPs in double-membrane organisms and evolutionarily related eukaryotic organelles. We also have employed diverse methodologies to confirm that some candidate OMPs do, in fact, form amphiphilic β-barrels and are surface-exposed in T. pallidum. These studies have led to a structural homology model for BamA and established the bipartite topology of the T. pallidum repeat (Tpr) family of proteins. Recent bioinformatics has identified several structural orthologs for well-characterized Gram-negative OMPs, suggesting that the T. pallidum OMP repertoire is more Gram-negative-like than previously supposed. Lipoprotein adhesins and proteases on the spirochete surface also may contribute to disease pathogenesis and protective immunity.
Topics: Bacterial Outer Membrane Proteins; Humans; Periplasm; Syphilis; Treponema pallidum
PubMed: 28849315
DOI: 10.1007/82_2017_44 -
Genome Biology Nov 2014
Topics: Genomics; High-Throughput Nucleotide Sequencing; Humans; Klebsiella pneumoniae; Treponema pallidum
PubMed: 25417942
DOI: 10.1186/s13059-014-0528-6 -
Journal of Clinical Laboratory Analysis Apr 2022Pathogens can affect host cells in various ways, and the same effect can be found in the Treponema pallidum acting on the endothelium of host vessels, and the mechanism... (Review)
Review
Pathogens can affect host cells in various ways, and the same effect can be found in the Treponema pallidum acting on the endothelium of host vessels, and the mechanism is often complex and multiple. Based on the existing T. pallidum of a cognitive framework, the first concerns involving T. pallidum or the bacteria protein directly acted on vascular endothelial cells of the host, the second concerns mainly involved in the process of T. pallidum infection in vivo blood lipid change, secretion of cytokines and the interactions between immune cells indirectly. Through both direct and indirect influence, this study explores the role of host by T. pallidum infect in the process of the vascular endothelium.
Topics: Endothelial Cells; Endothelium, Vascular; Globus Pallidus; Humans; Syphilis; Treponema; Treponema pallidum
PubMed: 35274369
DOI: 10.1002/jcla.24318 -
PloS One 2020Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). Until now, only a single TEN strain, Bosnia A, has been completely...
Whole genome sequence of the Treponema pallidum subsp. endemicum strain Iraq B: A subpopulation of bejel treponemes contains full-length tprF and tprG genes similar to those present in T. p. subsp. pertenue strains.
Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). Until now, only a single TEN strain, Bosnia A, has been completely sequenced. The only other laboratory TEN strain available, Iraq B, was isolated in Iraq in 1951 by researchers from the US Centers for Disease Control and Prevention. In this study, the complete genome of the Iraq B strain was amplified as overlapping PCR products and sequenced using the pooled segment genome sequencing method and Illumina sequencing. Total average genome sequencing coverage reached 3469×, with a total genome size of 1,137,653 bp. Compared to the genome sequence of Bosnia A, a set of 37 single nucleotide differences, 4 indels, 2 differences in the number of tandem repetitions, and 18 differences in the length of homopolymeric regions were found in the Iraq B genome. Moreover, the tprF and tprG genes that were previously found deleted in the genome of the TEN Bosnia A strain (spanning 2.3 kb in length) were present in a subpopulation of TEN Iraq B and Bosnia A microbes, and their sequence was highly similar to those found in T. p. subsp. pertenue strains, which cause the disease yaws. The genome sequence of TEN Iraq B revealed close genetic relatedness between both available bejel-causing laboratory strains (i.e., Iraq B and Bosnia A) and also genetic variability within the bejel treponemes comparable to that found within yaws- or syphilis-causing strains. In addition, genetic relatedness to TPE strains was demonstrated by the sequence of the tprF and tprG genes found in subpopulations of both TEN Iraq B and Bosnia A. The loss of the tprF and tprG genes in most TEN microbes suggest that TEN genomes have been evolving via the loss of genomic regions, a phenomenon previously found among the treponemes causing both syphilis and rabbit syphilis.
Topics: Bacterial Outer Membrane Proteins; Bosnia and Herzegovina; Genes, Bacterial; Genome, Bacterial; Phylogeny; Syphilis; Treponema; Treponema pallidum; Treponemal Infections; Whole Genome Sequencing; Yaws
PubMed: 32236138
DOI: 10.1371/journal.pone.0230926 -
PLoS Neglected Tropical Diseases Jun 2022Yaws is a chronic, highly contagious skin and bone infection affecting children living in impoverished, remote communities. It is caused by Treponema pallidum subsp....
BACKGROUND
Yaws is a chronic, highly contagious skin and bone infection affecting children living in impoverished, remote communities. It is caused by Treponema pallidum subsp. pertenue. We report the prevalence of active yaws among elementary schoolchildren based on clinical and serological criteria in selected municipalities of Southern Philippines.
METHODS
From January to March 2017, exploratory cross-sectional surveys and screening of skin diseases were conducted in the Liguasan Marsh area of the provinces Maguindanao, Sultan Kudarat, and Cotabato. We included 9 municipalities and randomly selected one public elementary school per municipality. Members of students' households and the communities were also examined and treated. Yaws suspects and contacts had blood tests for treponemal and non-treponemal antibodies using Dual Pathway Platform and Treponema pallidum particle agglutination (TPPA) tests.
RESULTS
A total of 2779 children and adults were screened for any skin disease: 2291 students, 393 household members, and 95 community members. Among 210 yaws suspects and contacts, 150 consented to serologic tests. The estimated prevalence of active yaws among schoolchildren screened was 1 out of 2291 (0.04%). Among 2532 children who were 14 years old and younger, 4 (0.2%) had active yaws. Eight adult household contacts and community members had latent yaws and 2 had past yaws. Five out of 9 municipalities were endemic for yaws.
CONCLUSIONS
This study confirmed that the Philippines is endemic for yaws but at a low level in the schools surveyed. This is an under-estimation due to the limited sampling. The lack of proper disease surveillance after the eradication campaign in the 1960's has made yaws a forgotten disease and has led to its resurgence. Yaws surveillance is needed to determine the extent of yaws in the Philippines and to help develop a strategy to eradicate yaws by 2030.
Topics: Adolescent; Adult; Child; Cross-Sectional Studies; Humans; Philippines; Seroepidemiologic Studies; Treponema; Treponema pallidum; Yaws
PubMed: 35648735
DOI: 10.1371/journal.pntd.0010447 -
Current Protocols Aug 2022Although the isolation of Treponema pallidum subsp. pallidum (T. pallidum) from a syphilis patient dates to 1912, for the duration of the 20 century, this pathogen has...
Although the isolation of Treponema pallidum subsp. pallidum (T. pallidum) from a syphilis patient dates to 1912, for the duration of the 20 century, this pathogen has remained an exceedingly difficult organism to study due to the lack of a system to support its viability in vitro. This limitation, in turn, has precluded the application of genetic engineering techniques via transformation and subsequent selection of T. pallidum transformants. A recently described method for in vitro cultivation of T. pallidum, however, has made it possible for us to experiment with transformation and selection methods. Here we describe the approach that we adopted to successfully transform T. pallidum with foreign DNA and select the resulting recombinant strain using kanamycin. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Transformation of T. pallidum Support Protocol 1: Quantification of T. pallidum in suspensions using dark-field microscopy Support Protocol 2: Counting cells using a hemacytometer Basic Protocol 2: Selection, initial passaging, and expansion of transformed cultures Basic Protocol 3: Isolation of a clonal strain through limiting dilution.
Topics: Humans; Syphilis; Treponema; Treponema pallidum
PubMed: 35976045
DOI: 10.1002/cpz1.507 -
Molecular Oral Microbiology Jun 2023The Msp protein complex and the serine protease dentilisin are the best-characterized virulence factors in Treponema denticola, the major etiological agent of chronic...
The Msp protein complex and the serine protease dentilisin are the best-characterized virulence factors in Treponema denticola, the major etiological agent of chronic periodontitis. In addition to these outer sheath factors, the cysteine protease dentipain contributes to pathogenicity, but its secretion, processing, cellular localization, and role in T. denticola virulence are not fully understood. In this study, we found that full-sized dentipain (74-kDa) and the 52-kDa truncated form of the enzyme are located, respectively, in the outer sheath derived from T. denticola dentilisin- and the Msp-deficient mutants. Furthermore, dentipain was barely detected in the wild-type strain. These results suggest that dentilisin and Msp, the major outer sheath proteins, are involved in the secretion and maturation of dentipain. Inactivation of the dentipain gene slowed the growth of T. denticola, and the effect was more profound in serum-free medium than in serum-containing medium. Several genes, including those encoding transporters and methyl-accepting chemotaxis proteins, were differentially expressed in the dentipain-deficient mutant. Furthermore, the mutant strain was more hydrophobic than the wild-type strain. Finally, the mutant showed less autoaggregation activity and adhesion to IgG in a serum-free medium than the wild-type strain. These findings suggest that dentipain contributes to the virulence of T. denticola by facilitating adhesion and acquisition of nutrients essential for colonization and proliferation in the gingival crevice under serum-rich conditions.
Topics: Treponema denticola; Bacterial Proteins; Chymotrypsin; Cysteine Proteases; Peptide Hydrolases; Treponema
PubMed: 36641800
DOI: 10.1111/omi.12406