Analysis of subsp. predicted outer membrane proteins (OMPeomes) in 21 clinical samples: variant sequences are predominantly surface-exposed.

The incidence of syphilis, a sexually transmitted disease caused by the subsp. (TPA), has been surging globally despite effective antibiotic therapy. A new strategy for syphilis control is the development of a multi-component syphilis vaccine with global efficacy, which requires the identification of surface-exposed candidate vaccinogens and the determination of their antigenic diversity within circulating TPA strains.

Sequence variability of BamA and FadL candidate vaccinogens suggests divergent evolutionary paths of outer membrane proteins.

Knowledge of subspecies () outer membrane protein (OMP) sequence variability is essential for understanding spirochete proliferation within endemic populations as well as the design of a globally effective syphilis vaccine. Our group has identified extracellular loops (ECLs) of BamA (TP0326) and members of the FadL family (TP0548, TP0856, TP0858, TP0859, and TP0865) as potential components of a multivalent vaccine cocktail. As part of a consortium to explore strain diversity, we mapped the variability of BamA and FadL orthologs in 186 strains from Malawi, China, and Colombia onto predicted 3D structures.

Modeling the Impact of Time to Treatment on Syphilis Prevalence: A Theoretical Mathematical Model of People Living With HIV in Colombia.

Background: Syphilis disproportionately affects people living with HIV (PLWH). Although screening is widely done for syphilis control, there are significant delays with time to treatment reaching 30 days in some settings in Colombia. Our study aimed to model the impact of reducing time to treatment on syphilis prevalence among PLWH in Colombia.

High prevalence of Haemophilus ducreyi among patients with suspected primary syphilis in Malawi, 2019-2022.

Background: As syphilis rates have increased globally, chancroid has dramatically declined as a cause of genital ulcer disease (GUD).

Methods: We recruited patients ≥18 years presenting to an STI clinic with GUD from Lilongwe, Malawi from November 2019 - April 2022. Lesion exudates were tested by darkfield microscopy (DFM) and polymerase chain reaction (PCR) for Treponema pallidum (TP), and by PCR for Haemophilus ducreyi (HD), herpes simplex virus (HSV) and Chlamydia trachomatis (CT).

Barriers and facilitators of participation in syphilis vaccine trials: a qualitative analysis to inform trial design and community engagement in the United States.

Amidst resurging syphilis infection rates, increasing efforts are being made towards development of a syphilis vaccine. This study aims to identify barriers and facilitators of syphilis vaccine trial participation among priority groups for early phase studies. We conducted interviews with English-speaking individuals ≥18 years old recruited from an infectious disease clinic, a sexually transmitted infection (STI) testing site, an online research bulletin board, and HIV community advisory boards in North Carolina from April 2021-June 2022.

Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.

The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies against Treponema pallidum (TPA), we used Pyrococcus furiosus thioredoxin (PfTrx) to display extracellular loops (ECLs) from three TPA outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded β-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). We identified five immunodominant loops from the FadL orthologs TP0856, TP0858 and TP0865 by immunoblotting and ELISA.

Development and utilization of expressing green fluorescent protein to study spirochete-host interactions and antibody-mediated clearance: expanding the toolbox for syphilis research.

Syphilis is a sexually transmitted infection caused by the highly invasive and immunoevasive spirochetal pathogen subsp. (). Untreated syphilis can lead to infection of multiple organ systems, including the central nervous system.

Immunodominant extracellular loops of FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.

The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies (Abs) against (), we used thioredoxin (Trx) to display extracellular loops (ECLs) from three outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded β-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). Five ECLs from the FadL orthologs TP0856, TP0858 and TP0865 were immunodominant.

New Pathways in Syphilis Vaccine Development.

The New Pathways in Syphilis Vaccine Development meeting was held before the start of the STI & HIV 2023 World Congress as a pre-meeting symposium to highlight recent advances in the development of an effective syphilis vaccine and discuss the challenges still faced by investigators. Internationally renowned public health officials, clinical investigators, and basic researchers from academia, government, and community-based organizations met on July 24, 2023, in Chicago, Illinois. Four speakers discussed key research findings in syphilis vaccine development, which included antigen selection, identification of epitopes associated with protective immunity, and delivery platforms, with great emphasis on development of chimeric antigens.

Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

Background: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations.

Clinical Presentation of Early Syphilis and Genomic Sequences of Treponema pallidum Strains in Patient Specimens and Isolates Obtained by Rabbit Inoculation.

Background: The global resurgence of syphilis necessitates vaccine development.

Methods: We collected ulcer exudates and blood from 17 participants with primary syphilis (PS) and skin biopsies and blood from 51 patients with secondary syphilis (SS) in Guangzhou, China, for Treponema pallidum subsp pallidum (TPA) quantitative polymerase chain reaction, whole genome sequencing (WGS), and isolation of TPA in rabbits.

Results: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens.

An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms.

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens.

Early syphilis in Guangzhou, China: presentation, molecular detection of , and genomic sequences in clinical specimens and isolates obtained by rabbit infectivity testing.

Background: The global resurgence of syphilis requires novel prevention strategies. Whole genome sequencing (WGS) of ( ) using different specimen types is essential for vaccine development.

Methods: Patients with primary (PS) and secondary (SS) syphilis were recruited in Guangzhou, China.

Use of Epivolve phage display to generate a monoclonal antibody with opsonic activity directed against a subdominant epitope on extracellular loop 4 of BamA (TP0326).

Introduction: Syphilis, a sexually transmitted infection caused by the spirochete (), is resurging globally. 's repertoire of outer membrane proteins (OMPs) includes BamA (β-barrel assembly machinery subunit A/TP0326), a bipartite protein consisting of a 16-stranded β-barrel with nine extracellular loops (ECLs) and five periplasmic POTRA (polypeptide transport-associated) domains. BamA ECL4 antisera promotes internalization of by rabbit peritoneal macrophages.

Clinical and genomic diversity of A global, multi-center study of early syphilis to inform vaccine research.

Background: The continuing increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We conducted a multi-center, observational study to explore subsp. ( ) molecular epidemiology essential for vaccine research by analyzing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data.

Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4-6 weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5-13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19.

BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals.

The RNA polymerase alternative σ factor RpoS in Borrelia burgdorferi (Bb), the Lyme disease pathogen, is responsible for programmatic-positive and -negative gene regulation essential for the spirochete's dual-host enzootic cycle. RpoS is expressed during tick-to-mammal transmission and throughout mammalian infection. Although the mammalian-phase RpoS regulon is well described, its counterpart during the transmission blood meal is unknown.

High-throughput nanopore sequencing of tandem repeat genes and reveals clade-specific patterns and recapitulates global whole genome phylogeny.

Sequencing of most genomes excludes repeat regions in and the gene, encoding the acidic repeat protein (). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence and genes from 212 clinical samples collected from ten countries on six continents. Both and repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging.

A suite of PCR-LwCas13a assays for detection and genotyping of Treponema pallidum in clinical samples.

The performance of commonly used assays for diagnosis of syphilis varies considerably depending on stage of infection and sample type. In response to the need for improved syphilis diagnostics, we develop assays that pair PCR pre-amplification of the tpp47 gene of Treponema pallidum subsp. pallidum with CRISPR-LwCas13a.

Extracellular Loops of the Treponema pallidum FadL Orthologs TP0856 and TP0858 Elicit IgG Antibodies and IgG-Specific B-Cells in the Rabbit Model of Experimental Syphilis.

The resurgence of syphilis in the new millennium has called attention to the importance of a vaccine for global containment strategies. Studies with immune rabbit serum (IRS) indicate that a syphilis vaccine should elicit antibodies (Abs) that promote opsonophagocytosis of treponemes by activated macrophages. The availability of three-dimensional models for Treponema pallidum's () repertoire of outer membrane proteins (OMPs) provides an architectural framework for identification of candidate vaccinogens with extracellular loops (ECLs) as the targets for protective Abs.

Bacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity.

Gastrointestinal microbes respond to biochemical metabolites that coordinate their behaviors. Here, we demonstrate that bacterial indole functions as a multifactorial mitigator of Klebsiella grimontii and Klebsiella oxytoca pathogenicity. These closely related microbes produce the enterotoxins tilimycin and tilivalline; cytotoxin-producing strains are the causative agent of antibiotic-associated hemorrhagic colitis and have been associated with necrotizing enterocolitis of premature infants.