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Healthcare (Basel, Switzerland) Dec 2023A review of the association between microbes and mental illness is performed, including the history, relevant definitions, infectious agents associated with mental... (Review)
Review
A review of the association between microbes and mental illness is performed, including the history, relevant definitions, infectious agents associated with mental illnesses, complex interactive infections, total load theory, pathophysiology, psychoimmunology, psychoneuroimmunology, clinical presentations, early-life infections, clinical assessment, and treatment. Perspectives on the etiology of mental illness have evolved from demonic possession toward multisystem biologically based models that include gene expression, environmental triggers, immune mediators, and infectious diseases. Microbes are associated with a number of mental disorders, including autism, schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders, as well as suicidality and aggressive or violent behaviors. Specific microbes that have been associated or potentially associated with at least one of these conditions include , , , Borna disease virus, (Lyme disease), , , coronaviruses (e.g., SARS-CoV-2), , cytomegalovirus, enteroviruses, Epstein-Barr virus, hepatitis C, herpes simplex virus, human endogenous retroviruses, human immunodeficiency virus, human herpesvirus-6 (HHV-6), human T-cell lymphotropic virus type 1, influenza viruses, measles virus, , , rubella virus, Group A (PANDAS), , , (syphilis), , and West Nile virus. Recognition of the microbe and mental illness association with the development of greater interdisciplinary research, education, and treatment options may prevent and reduce mental illness morbidity, disability, and mortality.
PubMed: 38200989
DOI: 10.3390/healthcare12010083 -
Euro Surveillance : Bulletin Europeen... Aug 2023BackgroundLyme borreliosis (LB) is the most common tick-borne disease (TBD) in France. Forestry workers are at high risk of TBD because of frequent exposure to tick...
BackgroundLyme borreliosis (LB) is the most common tick-borne disease (TBD) in France. Forestry workers are at high risk of TBD because of frequent exposure to tick bites.AimWe aimed to estimate the seroprevalence of sensu lato and tick-borne encephalitis virus (TBEV) antibodies among forestry workers in northern France. We compared seroprevalence by geographical area and assessed factors associated with seropositivity.MethodsBetween 2019 and 2020, we conducted a randomised cross-sectional seroprevalence survey. sl seropositivity was defined as positive ELISA and positive or equivocal result in western blot. Seropositivity for TBEV was defined as positive result from two ELISA tests, confirmed by serum neutralisation. We calculated weighted seroprevalence and adjusted prevalence ratios to determine association between potential risk factors and seropositivity.ResultsA total of 1,778 forestry workers participated. Seroprevalence for sl was 15.5% (95% confidence interval (CI): 13.9-17.3), 3.5 times higher in the eastern regions than in the western and increased with seniority and with weekly time in a forest environment. Seroprevalence was 2.5 times higher in forestry workers reporting a tick bite during past years and reporting usually not removing ticks rapidly. Seroprevalence for TBEV was 0.14% (95% CI: 0.05-0.42).ConclusionWe assessed for the first time seroprevalence of sl and TBEV antibodies among forestry workers in northern France. These results will be used, together with data on LB and tick-borne encephalitis (TBE) incidence and on exposure to tick-bites, to target prevention programmes.
Topics: Animals; Humans; Borrelia burgdorferi; Lyme Disease; Encephalitis Viruses, Tick-Borne; Seroepidemiologic Studies; Forestry; Cross-Sectional Studies; Antibodies, Bacterial; Antibodies, Viral; Tick-Borne Diseases; Encephalitis, Tick-Borne; Ticks; Bites and Stings; Risk Factors; France
PubMed: 37561054
DOI: 10.2807/1560-7917.ES.2023.28.32.2200961 -
MBio Oct 2023Lyme disease is a major tick-borne infection caused by a bacterial pathogen called , which is transmitted by ticks and affects hundreds of thousands of people every...
Lyme disease is a major tick-borne infection caused by a bacterial pathogen called , which is transmitted by ticks and affects hundreds of thousands of people every year. These bacterial pathogens are distinct from other genera of microbes because of their distinct features and ability to transmit a multi-system infection to a range of vertebrates, including humans. Progress in understanding the infection biology of Lyme disease, and thus advancements towards its prevention, are hindered by an incomplete understanding of the microbiology of , partly due to the occurrence of many unique borrelial proteins that are structurally unrelated to proteins of known functions yet are indispensable for pathogen survival. We herein report the use of diverse technologies to examine the structure and function of a unique protein, annotated as BB0238-an essential virulence determinant. We show that the protein is structurally organized into two distinct domains, is involved in multiplex protein-protein interactions, and facilitates tick-to-mouse pathogen transmission by aiding microbial evasion of early host cellular immunity. We believe that our findings will further enrich our understanding of the microbiology of potentially impacting the future development of novel prevention strategies against a widespread tick-transmitted infection.
Topics: Animals; Humans; Mice; Borrelia; Immune Evasion; Lyme Disease; Borrelia burgdorferi; Ticks; Ixodes
PubMed: 37830812
DOI: 10.1128/mbio.02135-23 -
Animals : An Open Access Journal From... Jun 2023There are limited data on Lyme borreliosis (LB), a tick-borne disease caused by the sensu lato complex, in horses. Seropositivity is not necessarily associated with...
There are limited data on Lyme borreliosis (LB), a tick-borne disease caused by the sensu lato complex, in horses. Seropositivity is not necessarily associated with clinical disease. Data on seropositivity against and in German horses are sparse. Therefore, serum samples from horses ( = 123) suspected of having Lyme borreliosis and clinically healthy horses ( = 113) from the same stables were tested for specific antibodies against sensu lato and . The samples were screened for antibodies against (ELISA and an IgG line immunoblot assay). Furthermore, the samples were examined for antibodies against and with a validated rapid in-house test (SNAP 4Dx Plus ELISA). The clinical signs of suspect horses included lameness ( = 36), poor performance ( = 19), and apathy ( = 12). Twenty-three percent ( = 26) of suspect horses and 17% ( = 18) of clinically healthy horses were seropositive for having a sensu lato infection ( = 0.371), showing that the detection of specific antibodies against alone is not sufficient for a diagnosis of equine LB. seropositivity and seropositivity against both pathogens was 20%/6% in suspect horses and 16%/2% in the clinically healthy population, showing only minor differences ( = 0.108). Unspecific testing for antibodies against without clinical suspicion of Lyme borreliosis is not recommended since the clinical relevance of seropositivity against sensu lato remains to be elucidated.
PubMed: 37370494
DOI: 10.3390/ani13121984 -
BioRxiv : the Preprint Server For... Jun 2023Lyme disease, caused by an infection with the spirochete , is the most common vector-borne disease in North America. strains harbor extensive genomic and proteomic...
Lyme disease, caused by an infection with the spirochete , is the most common vector-borne disease in North America. strains harbor extensive genomic and proteomic variability and further comparison is key to understanding the spirochetes infectivity and biological impacts of identified sequence variants. To achieve this goal, both transcript and mass spectrometry (MS)-based proteomics was applied to assemble peptide datasets of laboratory strains B31, MM1, B31-ML23, infective isolates B31-5A4, B31-A3, and 297, and other public datasets, to provide a publicly available Borrelia PeptideAtlas http://www.peptideatlas.org/builds/borrelia/. Included is information on total proteome, secretome, and membrane proteome of these strains. Proteomic data collected from 35 different experiment datasets, with a total of 855 mass spectrometry runs, identified 76,936 distinct peptides at a 0.1% peptide false-discovery-rate, which map to 1,221 canonical proteins (924 core canonical and 297 noncore canonical) and covers 86% of the total base B31 proteome. The diverse proteomic information from multiple isolates with credible data presented by the Borrelia PeptideAtlas can be useful to pinpoint potential protein targets which are common to infective isolates and may be key in the infection process.
PubMed: 37398146
DOI: 10.1101/2023.06.16.545244 -
PLoS Genetics Jul 2023Borrelia burgdorferi, a causative agent of Lyme disease, contains the most segmented bacterial genome known to date, with one linear chromosome and over twenty plasmids....
Borrelia burgdorferi, a causative agent of Lyme disease, contains the most segmented bacterial genome known to date, with one linear chromosome and over twenty plasmids. How this unusually complex genome is organized, and whether and how the different replicons interact are unclear. We recently demonstrated that B. burgdorferi is polyploid and that the copies of the chromosome and plasmids are regularly spaced in each cell, which is critical for faithful segregation of the genome to daughter cells. Regular spacing of the chromosome is controlled by two separate partitioning systems that involve the protein pairs ParA/ParZ and ParB/Smc. Here, using chromosome conformation capture (Hi-C), we characterized the organization of the B. burgdorferi genome and the interactions between the replicons. We uncovered that although the linear chromosome lacks contacts between the two replication arms, the two telomeres are in frequent contact. Moreover, several plasmids specifically interact with the chromosome oriC region, and a subset of plasmids interact with each other more than with others. We found that Smc and the Smc-like MksB protein mediate long-range interactions on the chromosome, but they minimally affect plasmid-chromosome or plasmid-plasmid interactions. Finally, we found that disruption of the two partition systems leads to chromosome restructuring, correlating with the mis-positioning of chromosome oriC. Altogether, this study revealed the conformation of a complex genome and analyzed the contribution of the partition systems and SMC family proteins to this organization. This work expands the understanding of the organization and maintenance of multipartite bacterial genomes.
Topics: Borrelia burgdorferi; Plasmids; Replicon; Genome, Bacterial; Telomere; Bacterial Proteins; DNA, Bacterial
PubMed: 37494383
DOI: 10.1371/journal.pgen.1010857 -
The Journal of Clinical Investigation Sep 2023BACKGROUNDAutoimmune diseases often have strong genetic associations with specific HLA-DR alleles. The synovial lesion in chronic inflammatory forms of arthritis shows...
BACKGROUNDAutoimmune diseases often have strong genetic associations with specific HLA-DR alleles. The synovial lesion in chronic inflammatory forms of arthritis shows marked upregulation of HLA-DR molecules, including in postinfectious Lyme arthritis (LA). However, the identity of HLA-DR-presented peptides, and therefore the reasons for these associations, has frequently remained elusive.METHODSUsing immunopeptidomics to detect HLA-DR-presented peptides from synovial tissue, we identified T cell epitopes from 3 extracellular matrix (ECM) proteins in patients with postinfectious LA, identified potential Borreliella burgdorferi-mimic (Bb-mimic) epitopes, and characterized T and B cell responses to these peptides or proteins.RESULTSOf 24 postinfectious LA patients, 58% had CD4+ T cell responses to at least 1 epitope of 3 ECM proteins, fibronectin-1, laminin B2, and/or collagen Vα1, and 17% of 52 such patients had antibody responses to at least 1 of these proteins. Patients with autoreactive T cell responses had significantly increased frequencies of HLA-DRB1*04 or -DRB1*1501 alleles and more prolonged arthritis. When tetramer reagents were loaded with ECM or corresponding Bb-mimic peptides, binding was only with the autoreactive T cells. A high percentage of ECM-autoreactive CD4+ T cells in synovial fluid were T-bet-expressing Th1 cells, a small percentage were RoRγt-expressing Th17 cells, and a minimal percentage were FoxP3-expressing Tregs.CONCLUSIONAutoreactive, proinflammatory CD4+ T cells and autoantibodies develop to ECM proteins in a subgroup of postinfectious LA patients who have specific HLA-DR alleles. Rather than the traditional molecular mimicry model, we propose that epitope spreading provides the best explanation for this example of infection-induced autoimmunity.FUNDINGSupported by National Institute of Allergy and Infectious Diseases R01-AI101175, R01-AI144365, and F32-AI125764; National Institute of Arthritis and Musculoskeletal and Skin Diseases K01-AR062098 and T32-AR007258; NIH grants P41-GM104603, R24-GM134210, S10-RR020946, S10-OD010724, S10-OD021651, and S10-OD021728; and the G. Harold and Leila Y. Mathers Foundation, the Eshe Fund, and the Lyme Disease and Arthritis Research Fund at Massachusetts General Hospital.
Topics: Humans; Autoimmunity; Extracellular Matrix Proteins; Lyme Disease; Borrelia burgdorferi; Arthritis; HLA-DRB1 Chains; Peptides; Epitopes, T-Lymphocyte
PubMed: 37471146
DOI: 10.1172/JCI161170 -
Pathogens (Basel, Switzerland) Oct 2023Lyme Borreliosis (LB), caused by sensu lato (s [...].
Lyme Borreliosis (LB), caused by sensu lato (s [...].
PubMed: 37887787
DOI: 10.3390/pathogens12101271 -
Nature Communications Mar 2024Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly...
Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease.
Topics: Mice; Animals; Humans; Borrelia burgdorferi; Lyme Disease; Ixodes; Secretoglobins
PubMed: 38503741
DOI: 10.1038/s41467-024-45983-9 -
PloS One 2023Lyme disease, caused by vector-borne Borrelia bacteria, can present with diverse multi-system symptoms that resemble other conditions. The objective of this study was to...
Lyme disease, caused by vector-borne Borrelia bacteria, can present with diverse multi-system symptoms that resemble other conditions. The objective of this study was to evaluate disease presentations and Borrelia seroreactivity in individuals experiencing a spectrum of chronic and complex illnesses. We recruited 157 participants from Eastern Canada who reported one or more diagnoses of Lyme disease, neurological, rheumatic, autoimmune, inflammatory, gastrointestinal, or cardiovascular illnesses, or were asymptomatic and presumed healthy. Intake categories were used to classify participants based on their perceived proximity to Lyme disease, distinguishing between those with a disclosed history of Borrelia infection, those with lookalike conditions (e.g. fibromyalgia syndrome), and those with unrelated ailments (e.g. intestinal polyps). Participants completed three questionnaires, the SF-36 v1, SIQR, and HMQ, to capture symptoms and functional burden, and provided blood serum for analysis at an accredited diagnostic lab. Two-tiered IgG and IgM serological assessments (whole cell ELISA and Western blot) were performed in a blinded fashion on all samples. The pattern of symptoms and functional burden were similarly profound in the presumptive Lyme and Lyme-like disease categories. Borrelia seroprevalence across the study cohort was 10% for each of IgG and IgM, and occurred within and beyond the Lyme disease intake category. Western blot positivity in the absence of reactive ELISA was also substantial. Fibromyalgia was the most common individual diagnostic tag disclosed by two-tier IgG-positive participants who did not report a history of Lyme disease. Within the IgG seropositive cohort, the presence of antibodies against the 31 kDa Outer Surface Protein A (OspA) was associated with significantly better health outcomes. Previously, this marker has been linked to treatment-refractory Lyme arthritis. Overall, our findings support prior observations of phenotypic overlap between Lyme and other diseases. Seropositivity associated with non-specific symptoms and functional impairment warrants further mechanistic investigation and therapeutic optimization.
Topics: Humans; Borrelia; Fibromyalgia; Seroepidemiologic Studies; Canada; Lyme Disease; Chronic Disease; Antibodies, Bacterial; Immunoglobulin G; Immunoglobulin M; Borrelia burgdorferi
PubMed: 37939060
DOI: 10.1371/journal.pone.0291382