A5052257198- Syphilis Diagnosis and Treatment
- Reproductive tract infections research
- Virology and Viral Diseases
- Immunodeficiency and Autoimmune Disorders
- HIV/AIDS oral health manifestations
- Cervical Cancer and HPV Research
- Sex work and related issues
- Infectious Diseases and Mycology
- Forensic and Genetic Research
- Reproductive System and Pregnancy
University of Washington
2020-2024
Harborview Medical Center
2022-2023
Seattle University
2021
In spite of its immutable susceptibility to penicillin, Treponema pallidum ( T . ) subsp. continues cause millions cases syphilis each year worldwide, resulting in significant morbidity and mortality underscoring the urgency developing an effective vaccine curtail spread infection. Several technical challenges, including absence vitro culture system until very recently, have hampered efforts catalog diversity strains collected worldwide. Here, we provide near-complete genomes from 196...
Despite more than a century of research, genetic manipulation Treponema pallidum subsp. ( T . ), the causative agent syphilis, has not been successful. The lack engineering tools severely limited understanding mechanisms behind success as pathogen. A recently described method for in vitro cultivation , however, made it possible to experiment with transformation and selection protocols this Here, we describe an approach that successfully replaced tprA tp0009 ) pseudogene SS14 strain kanamycin...
Background The TprK protein of the syphilis agent, Treponema pallidum subsp. ( T . ), undergoes antigenic variation in seven discrete variable (V) regions via non-reciprocal segmental gene conversion. These recombination events transfer information from a repertoire 53 silent chromosomal donor cassettes (DCs) into single tprK expression site to continually generate variants. Several lines research developed over last two decades support theory that this mechanism is central ’s ability for...
BackgroundPenicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both in vitro and vivo, three marketed antibiotics with adequate pharmacological properties treat syphilis.MethodsWe used an culturing system of T. pallidum perform drug susceptibility testing applied quantitative PCR targeting tp0574 gene measure bacterial growth. To confirm vivo...
The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. (T. pallidum) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance controlled studies assess differential treponemal gene expression, generation loss-of-function mutants evaluate contribution specific genetic loci T. virulence. Building on this progress, we engineered SS14 strain express a red-shifted green fluorescent protein...
Given the resurgence of syphilis, research endeavors to improve current assays for serological diagnosis and management this disease are a priority. A proteome-scale platform high-throughput profiling humoral response
Background An effective syphilis vaccine should elicit antibodies to Treponema pallidum subsp. ( T . p ) surface antigens induce pathogen clearance through opsonophagocytosis. Although the combination of bioinformatics, structural, and functional analyses genes identify putative outer membrane proteins (OMPs) resulted in a list potential candidates, still very little is known about whether how transcription these regulated during infection. This knowledge gap limitation design, as immunity...
This manuscript explores the host humoral response to selected antigens of syphilis agent during infection evaluate their potential use as diagnostic tests and markers for treatment.
Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding acidic protein ( arp ). As a first step to understanding evolution function these genes proteins they encode, we developed protocol nanopore sequence from 212 clinical samples collected ten countries on six continents. Both structures recapitulate whole genome phylogeny, with subclade-specific patterns emerging. The number repeats is average appears be higher Nichols-like clade...
Abstract Although the isolation of Treponema pallidum subsp. ( T. ) from a syphilis patient dates to 1912, for duration 20 th century, this pathogen has remained an exceedingly difficult organism study due lack system support its viability in vitro . This limitation, turn, precluded application genetic engineering techniques via transformation and subsequent selection transformants. A recently described method cultivation , however, made it possible us experiment with methods. Here we...
A patient with unilateral cervical lymphadenopathy suspicious for malignancy underwent a fine needle aspiration. Histology demonstrated mixed inflammatory infiltrates abundant spirochetes. Sufficient spirochete DNA was extracted from paraffin-embedded tissue sections to obtain the near-complete genome sequence of macrolide-resistant strain belonging SS14 omega Treponema pallidum .
SUMMARY The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. ( T. ) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance controlled studies assess differential treponemal gene expression, generation loss-of-function mutants evaluate contribution specific genetic loci virulence. Building on this progress, we engineered SS14 strain express a red-shifted Green Fluorescent Protein...
The TprK protein of the syphilis agent, Treponema pallidum subsp. ( T. ), undergoes antigenic variation in seven discrete variable (V) regions via non-reciprocal segmental gene conversion. These recombination events transfer information from a repertoire 53 silent chromosomal donor cassettes (DCs) into single tprK expression site to continually generate variants. Several lines research developed over last two decades support theory that this mechanism is central 's ability for immune...
Abstract Background Despite more than a century of research, genetic manipulation Treponema pallidum subsp. ( T. ), the causative agent syphilis, has not been successful. The lack engineering tools severely limited understanding mechanisms behind success as pathogen. A recently described method for in vitro cultivation pallidum, however, made it possible to experiment with transformation and selection protocols this Here, we describe an approach that successfully replaced tprA tp0009 )...
ABSTRACT Background Given the resurgence of syphilis, research endeavors to improve current assays for serological diagnosis and management this disease are a priority. A proteome-scale platform high-throughput profiling humoral response Treponema pallidum ( T. ) proteins during infection could identify antigens suitable ameliorate performance capabilities treponemal tests (TTs), which may require weeks become positive following infection, cannot distinguish between active previously treated...
Abstract Sequencing of most Treponema pallidum ( T. ) genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding acidic protein arp ). As a first step to understanding evolution function these genes proteins they encode, we developed protocol nanopore sequence from 212 clinical samples collected ten countries on six continents. Both structures recapitulate whole genome phylogeny, with subclade-specific patterns emerging. The number repeats is average appears be higher...
Abstract Background An effective syphilis vaccine should elicit antibodies to Treponema pallidum subsp. ( T. p. ) surface antigens induce pathogen clearance through opsonophagocytosis. Although the combination of bioinformatics, structural, and functional analyses genes identify putative outer membrane proteins (OMPs) resulted in a list potential candidates, still very little is known about whether how transcription these regulated during infection. This knowledge gap limitation design, as...
Abstract Background Treponema pallidum (T. pallidum) is transmitted from person to by direct contact with widespread dissemination early after acquisition. Current syphilis diagnostic testing limited darkfield microscopy visible lesions and serologic antibody detection. T. molecular diagnostics are urgently needed. Methods As part of a multicenter US treatment trial that completed enrollment in March 2022 (NCT 3637660), we randomized 249 adults infection 1 vs 3 weekly doses benzathine...
<h3>Background</h3> The recently described method for in vitro cultivation of the syphilis agent, Treponema pallidum subsp. (T. pallidum), paved way to transformation experiments genetically engineer this pathogen. demonstration that modified treponemes are attainable would represent a milestone research, destined revolutionize our approach understand mechanisms behind T. success as Here, first time we describe protocol successfully replaced tprA (tp0009) pseudogene SS14 strain with...
<h3>Background</h3> Penicillin G (PG), the current standard for syphilis treatment, has important drawbacks that hamper public health efforts to curtail spread of this infection, particularly in low- and middle-income countries where is still endemic. <h3>Methods</h3> To identify viable alternatives PG, we tested—both vitro vivo—three marketed antibiotics with adequate pharmacokinetic pharmacodynamic properties treat syphilis. <h3>Results</h3> We found linezolid, an oxazolidinone overcoming...
<h3>Background</h3> Syphilis, caused by the spirochete Treponema pallidum subsp. (T. pallidum), continues to be a significant global health concern. The diagnosis of syphilis mainly relies on assessing clinical manifestations and performing serologic testing detect treponemal non-treponemal antibodies discriminate between past present infection evaluate response treatment. Limitations, however, include that no test can among stages, sensitivity is low during very early stages infection. New...
<h3>Background</h3> An effective syphilis vaccine will be integral to efforts eradicate this disease. Promising candidates are surface antigens of the spirochete, Treponema pallidum subsp. (T. pallidum). These can targeted by vaccination-induced opsonic antibodies and mediate pathogen immune clearance. Defining correlates protection aid in identification best candidates. Here, we sought investigate whether immunization with variants T. Repeat C (TprC) protein conserved NH2-terminus TprK...
Abstract In spite of its immutable susceptibility to penicillin, Treponema pallidum ( T. ) subsp. continues cause millions cases syphilis each year worldwide, resulting in significant morbidity and mortality underscoring the urgency developing an effective vaccine curtail spread infection. Several technical challenges, including absence vitro culture system until very recently, have hampered efforts catalog diversity strains collected worldwide. Here, we provide near-complete genomes from...