Treponema pallidum, an obligate human pathogen, has an outer membrane (OM) whose physical properties, ultrastructure and composition differ markedly from those of phylogenetically distant Gram-negatives. We developed structural models for the outer membrane protein (OMP) repertoire of T. pallidum Nichols using solved Gram-negative structures, computational tools, and small angle X-ray scattering (SAXS) of selected recombinant periplasmic domains. The T. pallidum ‘OMPeome’ harbors two ‘stand-alone’ proteins (BamA and LptD) involved in OM biogenesis and four paralogous families involved in influx/efflux of small molecules: 8-stranded β-barrels, long-chain fatty acid transporters (FadLs), OM factors (OMFs) for efflux pumps, and T. pallidum repeat proteins (Tprs). BamA (TP0326), the central component of a BAM/TAM hybrid, possesses a highly flexible POTRA1-5 predicted to interact with TamB (TP0325). TP0515, an LptD ortholog, contains a novel, unstructured C-terminal domain that models inside the β-barrel. T. pallidum has four 8-stranded β-barrels, each containing positively charged extracellular loops that could contribute to pathogenesis. Three of five FadL-like orthologs have a novel α-helical, presumptively periplasmic C-terminal extension. SAXS and structural modeling further supported the bipartite membrane topology and tri-domain architecture of full-length members of the Tpr family. T. pallidum’s two efflux pumps presumably extrude noxious small molecules via four co-expressed OMFs with variably charged tunnels. For BamA, LptD and OMFs, we modeled the molecular machines that deliver their substrates into the OM or external milieu. The spirochete’s extended families of OM transporters collectively confer a broad capacity for nutrient uptake. The models also furnish a structural roadmap for vaccine development. Importance The unusual outer membrane (OM) of T. pallidum, the syphilis spirochete, is the ultrastructural basis for its well-recognized capacity for invasiveness, immune evasion, and persistence. In recent years, we have made considerable progress identifying T. pallidum’s repertoire of OMPs. Herein, we developed three-dimensional (3D) models for the T. pallidum Nichols OMPeome using structural modeling, bioinformatics, and solution scattering. The OM contains three families of OMP transporters, an OMP family involved in extrusion of noxious molecules, and two ‘stand alones’ involved in OM biogenesis. This work represents a major advance towards elucidating host-pathogen interactions during syphilis, understanding how T. pallidum, an extreme auxotroph, obtains a wide array of biomolecules from its obligate human host, and developing a vaccine with global efficacy.

People living with human immunodeficiency virus (HIV) are living longer since the advent of effective combined antiretroviral therapy (cART). While cART substantially decreases the risk of developing some cancers, HIV-infected individuals remain at high risk for Kaposi sarcoma, lymphoma and several solid tumors. Currently HIV-infected patients represent an aging group, and malignancies have become a leading cause of morbidity and mortality. Tailored cancer-prevention strategies are needed for this population. In this review we describe the etiologic agents and pathogenesis of common malignancies in the setting of HIV, as well as current evidence for cancer prevention strategies and screening programs.

Deconvolution of syphilis pathogenesis and selection of candidate syphilis vaccinogens requires detailed knowledge of the molecular architecture of the Treponema pallidum outer membrane (OM). The T. pallidum OM contains a low density of integral OM proteins, while the spirochete's many lipoprotein immunogens are periplasmic. TP0751, a lipoprotein with a lipocalin fold, is reportedly a surface-exposed protease/adhesin and protective antigen. The rapid expansion of calycin/lipocalin structures in the RCSB PDB database prompted a comprehensive reassessment of TP0751. Small angle X-ray scattering analysis of full-length protein revealed a bipartite topology consisting of an N-terminal, intrinsically disordered region (IDR) and the previously characterized C-terminal lipocalin domain. A DALI server query using the lipocalin domain yielded 97 hits, 52 belonging to the calycin superfamily, including 15 bacterial lipocalins, but no Gram-negative surface proteins. Surprisingly, Tpp17 (TP0435) was identified as a structural ortholog of TP0751. In silico docking predicted that TP0751 can bind diverse ligands along the rim of its eight-stranded β-barrel; high affinity binding of one predicted ligand, heme, to the lipocalin domain was demonstrated. qRT-PCR and immunoblotting revealed very low expression of TP0751 compared to other T. pallidum lipoproteins. Immunoblot analysis of immune rabbit serum failed to detect TP0751 antibodies, while only one of five patients with secondary syphilis mounted a discernible TP0751specific antibody response. In opsonophagocytosis assays, neither TP0751 nor Tpp17 antibodies promoted uptake of T. pallidum by rabbit peritoneal macrophages. Rabbits

Background Trading sex for drugs or money is common in substance abuse treatment patients, and this study evaluated prevalence and correlates of this behavior in women with cocaine use disorders initiating outpatient care. In addition, we examined the relation of sex trading status to treatment response in relation to usual care versus contingency management (CM), as well as predictors of continued involvement in sex trading over a 9-month period. Methods Women (N = 493) recruited from outpatient substance abuse treatment clinics were categorized according to histories of sex trading (n = 215, 43.6%) or not (n = 278). Results Women with a history of trading sex were more likely to be African American, older and less educated, and they had more severe employment problems and were more likely to be HIV positive than those without this history. Controlling for baseline differences, both groups responded equally to substance abuse treatment in terms of retention and abstinence outcomes. Fifty-four women (11.3%) reported trading sex within the next nine months. Predictors of continued involvement in trading sex included a prior history of such behaviors and achieving less abstinence during treatment. Each additional week of abstinence during treatment was associated with a 16% reduction in the likelihood of trading sex over the follow-up. Conclusions Because over 40% of women receiving community-based treatment for cocaine use disorders have traded sex for drugs or money and more than 10% persist in the behavior, more intensive and directed approaches toward addressing this HIV risk behavior are recommended.