Dataset Information

A Comparison of Treponema pallidum Subspecies pallidum Molecular Typing Systems: Multilocus Sequence Typing vs. Enhanced Centers for Disease Control and Prevention Typing.

ABSTRACT:

Background

At least 3 syphilis typing systems are proposed. Recent work suggests that multilocus sequence typing (MLST) may be superior to enhanced Centers for Disease Control and Prevention typing (ECDCT) by yielding a higher discriminatory power. The goal of this study was to compare the 2 systems and identify associations between neurosyphilis and strain types.

Methods

Multilocus sequence typing for tp0136, tp0548, and tp0705 was determined for DNA from 78 Treponema pallidum subspecies pallidum isolates propagated in rabbits, 10 oral and 10 genital or non-genital lesion swabs, and 10 blood samples from patients with syphilis. These samples were chosen because they were completely typeable by ECDCT. Using both systems, association between strain types and neurosyphilis, defined as a reactive cerebrospinal fluid Venereal Disease Research Laboratory test, was determined. Partial and complete ECDCT types were also determined for samples from different anatomical sites in 35 patients, and from blood and blood isolates (rabbit propagated) from 13 patients.

Results

The MLST type could be fully determined for 100 (92.6%) of 108 samples. Although MLST subdivided 3 common ECDCT types, it failed to distinguish among others. Neurosyphilis was more common in individuals infected with type 1.1.2 and tp0705 type 2 using MLST, and tp0548 type f using ECDCT. Enhanced Centers for Disease Control and Prevention typing was stable among anatomical sites and between patient-derived and rabbit propagated organisms.

Conclusions

Compared with ECDCT, MLST was not uniformly more discriminating. Both typing systems demonstrate that specific types may be more neurotropic than others.

SUBMITTER: Sahi SK

PROVIDER: S-EPMC8373628 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

A Comparison of Treponema pallidum Subspecies pallidum Molecular Typing Systems: Multilocus Sequence Typing vs. Enhanced Centers for Disease Control and Prevention Typing.

Sahi Sharon K SK Zahlan Jana M JM Tantalo Lauren C LC Marra Christina M CM

Sexually transmitted diseases 20210901 9

<h4>Background</h4>At least 3 syphilis typing systems are proposed. Recent work suggests that multilocus sequence typing (MLST) may be superior to enhanced Centers for Disease Control and Prevention typing (ECDCT) by yielding a higher discriminatory power. The goal of this study was to compare the 2 systems and identify associations between neurosyphilis and strain types.<h4>Methods</h4>Multilocus sequence typing for tp0136, tp0548, and tp0705 was determined for DNA from 78 Treponema pallidum su ...[more]

PMID: 34110749

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Project description:BackgroundThe increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.MethodsUsing the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.FindingsAmoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.InterpretationCephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.FundingEuropean Research Council.

Project description:BackgroundSyphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance.Methodology/principal findingsTwo researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, ?(2)?=?247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, ?(2)?=?102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited.Conclusions/significancePrimary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis.

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Project description:BackgroundYaws is a neglected tropical disease, caused by Treponema pallidum subsp. pertenue. The disease causes chronic lesions, primarily in young children living in remote villages in tropical climates. As part of a global yaws eradication campaign initiated by the World Health Organization, we sought to develop and evaluate a molecular typing method to distinguish different strains of T. pallidum subsp. pertenue for disease control and epidemiological purposes.Methods and principal findingsPublished genome sequences of strains of T. pallidum subsp. pertenue and pallidum were compared to identify polymorphic genetic loci among the strains. DNA from a number of existing historical Treponema isolates, as well as a subset of samples from yaws patients collected in Lihir Island, Papua New Guinea, were analyzed using these targets. From these data, three genes (tp0548, tp0136 and tp0326) were ultimately selected to give a high discriminating capability among the T. pallidum subsp. pertenue samples tested. Intragenic regions of these three target genes were then selected to enhance the discriminating capability of the typing scheme using short readily amplifiable loci. This 3-gene multilocus sequence typing (MLST) method was applied to existing historical human yaws strains, the Fribourg-Blanc simian isolate, and DNA from 194 lesion swabs from yaws patients on Lihir Island, Papua New Guinea. Among all samples tested, fourteen molecular types were identified, seven of which were found in patient samples and seven among historical isolates or DNA. Three types (JG8, TD6, and SE7) were predominant on Lihir Island.ConclusionsThis MLST approach allows molecular typing and differentiation of yaws strains. This method could be a useful tool to complement epidemiological studies in regions where T. pallidum subsp. pertenue is prevalent with the overall goals of improving our understanding of yaws transmission dynamics and helping the yaws eradication campaign to succeed.

Dataset Information

A Comparison of Treponema pallidum Subspecies pallidum Molecular Typing Systems: Multilocus Sequence Typing vs. Enhanced Centers for Disease Control and Prevention Typing.

Background

Methods

Results

Conclusions

Publications

A Comparison of Treponema pallidum Subspecies pallidum Molecular Typing Systems: Multilocus Sequence Typing vs. Enhanced Centers for Disease Control and Prevention Typing.

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