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Syphilis continues to be a significant global health concern. To define the extent of the IgG and IgA antibody reactome in patients with syphilis and identify reactive antigens and reactivity patterns that could facilitate early diagnosis and possibly serve as biomarkers for treatment response and staging, we developed a pan-proteomic microarray carrying 98.8% (1,009 antigens) of the annotated polypeptides of two subsp strains (Nichols and SS14). In this study, we probed the array with 217 sera collected pre- and post-treatment from 122 syphilis patients to detect IgG and IgA antibodies. Although a minimal IgA response to antigens were detected in these sera, with only 21 reactive targets on the array, corresponding to 20 antigens, significant IgG reactivity was detected to a total of 104 array protein spots, corresponding to 101 antigens, and roughly encompassing 10% of the pathogen's proteome. No targets were differentially recognized in pre-treatment sera when factoring in covariates such as syphilis stage, syphilis history, and human immunodeficiency virus status, but a significant decrease in reactivity to 82 antigens was detected in the sera collected post-treatment compared to sera collected at diagnosis. This work helped define the extent of the IgG and IgA antibody response in syphilis patients and identified antigens that could be further evaluated to improve treponemal serological tests. Antigens inducing a detectable IgA response in adults, albeit very few, could be further investigated as diagnostic markers.IMPORTANCEThis investigation improved our understanding of the IgG and IgA humoral response to virtually all proteins of subsp. ( ) during natural infection in patients with active and treated syphilis. Using samples collected pre- and post-treatment from individuals presenting with syphilis at different stages, human immunodeficiency virus status, and history of recurrent infection, we identified antigens that could be further investigated to improve early syphilis and congenital syphilis diagnosis and serve as possible biomarkers to monitor treatment response.

Current knowledge on immune cell interactions with Borrelia burgdorferi (Bb) derives mostly from studies done in vitro and ex vivo, which cannot assess host immunity to natural tick-delivered Bb within the complex architecture of host tissues. We report the first in vivo study on local and systemic immune responses to Bb during tick feeding on a surrogate reservoir host, in comparison with uninfected-tick and subcutaneously delivered Bb. We show that uninfected-tick and tick-transmitted Bb engaged mixed type-1/type-2/type-17 immune responses in the presence of anti-inflammatory IL-10, in contrast to a type-1 response induced by subcutaneously delivered Bb. Analyses of immune responses to tick-transmitted Bb in a reservoir host can enlighten immunity mechanisms that mediate persistence of Bb.

spp. are major zoonotic bacterial pathogens that can cause a range of diseases in both humans and animals, including gastroenteritis, septicemia, and typhoid fever. During intestinal colonization, relies on the coordinated action of the SPI-4 encoded type I secretion system (T1SS) and SPI-1 encoded type III secretion system (T3SS-1) to breach epithelial barriers. Although the T3SS-1 and its effectors have been widely studied, the T1SS and its associated effectors remain poorly characterized. The T1SS-secreted substrate SiiE binds to host cell surface mucins via its bacterial Ig-like (BIg) domain, facilitating the proper positioning of the T3SS-1 and subsequently triggering bacterial internalization. Given the critical role of the T1SS and SiiE in virulence, they may serve as promising targets for anti-virulence drug development. In this review, we provide an overview of the current knowledge on the T1SS, including its regulatory mechanisms, channel formation, and the functional properties of SiiE.

Leptospirosis is a globally significant severe infectious disease that affects a range of mammals. To understand its complex aetiopathogenesis, spp. are classified as pathogenic or saprophytic, with serum resistance a key differentiator of virulence. LIC13259 is a leptospiral surface lipoprotein that binds C8 of the host complement system; however, the molecular basis of this interaction has remained unclear. AlphaFold2 structural predictions, together with protein engineering, biochemical, and immunological validations, revealed that LIC13259 binds specifically to the C8γ subunit via thiol-disulfide exchange. Binding assays confirmed that LIC13259 from pathogenic, but not saprophytic, adheres to C8γ, preventing C8α binding, and enabling membrane attack complex evasion. Substitution of cysteine-133 with an alanine abolished both C8γ binding and complement inhibition. Removal (alanine substitution) of the target cysteine from C8γ prevented pathogenic LIC13259 binding, whereas removing LIC13259 cysteine-108, which forms a predicted intramolecular disulfide bond with cysteine-133, enhanced C8γ binding. These results identify an unprecedented cross-kingdom intermolecular disulfide bond mediating complement evasion and highlight the value of AlphaFold structural modeling, combined with targeted mutagenesis and biochemical validation, for discovering host-pathogen protein-protein interactions. The discovery of this novel immune evasion mechanism may allow recognition of this unique host-pathogen interaction in a range of diseases, while therapeutics and vaccines targeting such cross-kingdom disulfide-mediated mimicry may enable future infectious disease control. Leptospirosis is a globally important zoonotic disease of humans and animals, caused by the bacteria Leptospira. A central determinant of virulence is the ability for these bacteria to evade complement, a host defense system that assembles the membrane attack complex to eliminate pathogens. Here, we elucidate a novel immune evasion mechanism in which the leptospiral surface protein LIC13259 forms a disulfide bond with complement component C8γ, preventing binding of C8α. This interaction disrupts the membrane attack complex assembly and promotes bacterial survival. To our knowledge, this represents the first example of a cross-kingdom disulfide bond mediating bacterial pathogenesis. These findings provide novel insights into leptospiral immune modulation and demonstrate the power of AlphaFold-based structural predictions to reveal unique host-pathogen interactions.

Borrelia burgdorferi , the tick-borne agent of Lyme disease, is the causative agent of one of the most prevalent vector-borne infections in many regions worldwide. Despite extensive study, the biological functions of many of its protein and small RNA (sRNA) products remain poorly defined. Here, we confirm and extend the regulatory roles of the linear plasmid ( lp )17-encoded protein BBD18 and the sRNA SR0736 ( ittA ) in spirochete infectivity. Importantly, we identify a previously unrecognized regulatory function for an adjacent sRNA, SR0735 , underscoring lp17 as a key regulatory region in B. burgdorferi . Together, our findings highlight the bbd18 locus and its surrounding sRNA elements as an independent, multilayered regulatory module that controls gene products, including those required for mammalian infection. Defining how these three regulators shape gene expression and virulence will reveal new mechanisms underlying Lyme disease pathogenesis and may inform the development of new strategies to prevent this widespread illness.

Foodborne pathogen Salmonella can tolerate high concentrations of bile and even survive the harsh environment of the gall bladder. This study is significant as it explores the role of a novel antioxidant gene yqhD in bile salt susceptibility of Salmonella Typhimurium and Typhi. It highlights how the presence of gene yqhD , though advantageous in macrophages, reduces the Salmonella survival on bile salt exposure in vitro and in liver cell line HepG2. Deletion of yqhD increased the survival on bile stress exposure, which was attributed to its ability to induce the AcrAB efflux pump of Salmonella . A deeper understanding of how Salmonella modulates gene expression in response to bile stress could provide valuable insights into addressing the chronic carriage of Salmonella .

Lyme disease, caused by the spirochete Borrelia burgdorferi , is the most prevalent vector-borne infection in the Northern Hemisphere and continues to expand geographically. Although B. burgdorferi has a streamlined genome and minimal virulence repertoire, it establishes persistent infection through coordinated modulation of mammalian host immune responses. Here, we synthesize recent advances in the immunobiology of B. burgdorferi using a stage-structured framework that traces a tick-mediated vertebrate infection through systemic dissemination, tissue colonization, and chronic immune engagement. Emphasis is placed on post-2020 insights enabled by intravital imaging, single-cell transcriptomics, spatial profiling, and systems immunology, which have refined our understanding of endothelial transmigration, tissue-specific immune conditioning, disruption of germinal center responses, and failure of sterilizing immunity. We highlight how antigenic variation at the vls locus, complement evasion, and coordinated adhesin networks support dissemination and long-term tissue residency, while adaptive immune responses are redirected toward extrafollicular, non-sterilizing trajectories. These immune strategies differentially shape infection outcomes across host species, supporting asymptomatic persistence in reservoir hosts while driving inflammatory disease in humans. The review further examines antigen persistence, immune stalemate, and post-treatment inflammatory sequelae, integrating translational advances in diagnostics and prevention. By integrating an ecological context with mechanistic immunology and clinical insight, this review presents a contemporary framework for understanding how immune modulation by B. burgdorferi across spatial and temporal scales shapes host-pathogen coevolution and informs improved diagnostic strategies, vaccine development, and therapeutic intervention.

[...]settings contain complex microbial and chemical compositions, facilitating a high rate of horizontal gene transfer that enables reworking of cellular functions to allow rapid adaptation to new environmental conditions and hosts. Virulent L. interrogans, but not the saprophytic Leptospira biflexa, disrupt adherens junctions of endothelial and epithelial cells in vitro, resulting in loss of VE- and E-cadherins and disruption of the associated catenins, which link cadherins to the intracellular actin cytoskeleton. A clue to the molecular mechanisms for endothelial barrier disruption emerged from a study examining the crystal structures of 4 L. interrogans leucine-rich repeat (LRR) proteins [20]. [...]C3H/HeJ mice lacking TLR4 are more susceptible to leptospiral infection have a higher leptospiral burden than C3H mice with an intact TLR4 [25].

Periodontitis has a polymicrobial etiology within the framework of a complex microbial ecosystem. With advances in sequencing technologies, comprehensive studies to elucidate bacterial community differences have recently become possible. We used 454 sequencing of 16S rRNA genes to compare subgingival bacterial communities from 29 periodontally healthy controls and 29 subjects with chronic periodontitis. Amplicons from both the V1-2 and V4 regions of the 16S gene were sequenced, yielding 1 393 579 sequences. They were identified by BLAST against a curated oral 16S database, and mapped to 16 phyla, 106 genera, and 596 species. 81% of sequences could be mapped to cultivated species. Differences between health- and periodontitis-associated bacterial communities were observed at all phylogenetic levels, and UniFrac and principal coordinates analysis showed distinct community profiles in health and disease. Community diversity was higher in disease, and 123 species were identified that were significantly more abundant in disease, and 53 in health. Spirochaetes , Synergistetes and Bacteroidetes were more abundant in disease, whereas the Proteobacteria were found at higher levels in healthy controls. Within the phylum Firmicutes, the class Bacilli was health-associated, whereas the Clostridia , Negativicutes and Erysipelotrichia were associated with disease. These results implicate a number of taxa that will be targets for future research. Some, such as Filifactor alocis and many Spirochetes were represented by a large fraction of sequences as compared with previously identified targets. Elucidation of these differences in community composition provides a basis for further understanding the pathogenesis of periodontitis.

Background Current concepts suggest that a dysbiotic environment can promote ‘oral carcinomas.’ Microbiome studies on the oral cavity indicate changes in bacterial disposition in this condition. Yet, few focus on a lesser-known species, Treponema denticola , a motile periodontal pathogen, in addressing concerns related to oral carcinogenesis. Clinical studies find an enrichment of the Treponema genus in sites with oral cancer. Other research designs hint at Treponema denticola possessing both direct and indirect mechanisms to perpetrate damage in oral cancer. Methods We followed the Joanna Briggs Institute (JBI) methodology for this scoping review. The population, Concept and Context (PCC) were as follows: Population: adults with carcinomas in general/OSCC; Concept: T. denticola/Treponema and virulence factors; Context: Presence of T. denticola/Treponema and virulence factors in oral cavity tissues/fluids / or demonstrating role in carcinogenesis. The terms ‘ Adult OR population OR patient AND Treponema denticola OR T. denticola OR spirochete* OR treponema* AND oral cancer OR OSCC OR oral squamous cell carcinoma OR carcinoma OR metastasis OR epithelial-mesenchymal transition OR Oral cancer initiation , promotion , progression’ were adapted and searched across four different databases, retrieving all material published in English till 26 August 2024. Results Sixty-six articles were included in the scoping review following a full-text search, including 35 clinical studies, 21 reviews, 3 database studies, 4 in vitro studies, and 2 animal studies. Approximately 54% of the clinical studies found spirochetes or Trep o nema (genus/species) or its virulence factor abundant at cancer sites. Animal models also demonstrate the impact of Treponema denticola on tumour progression. Conclusions The genus Treponema and/or its virulence factors are detected in some oral carcinoma samples, indicating a possible association with advanced stages or deeper invasion. Future research can focus on its ability to induce malignant transformation and explore its potential as a candidate biomarker of oral carcinoma deserving validation.