Lyme borreliosis and medical wandering: what do patients think about multidisciplinary management? A qualitative study in the context of scientific and social controversy.

INTRODUCTION: To answer to patients' medical wandering, often due to "unexplained symptoms" of "unexplained diseases" and to misinformation, multidisciplinary care centers for suspected Lyme borreliosis (LB), such as the 5 Tick-Borne Diseases (TBDs) Reference Centers (TBD-RC), were created a few years ago in France, the Netherlands and Denmark. Our study consisted of a comprehensive analysis of the satisfaction of the patients managed at a TBD-RC for suspected LB in the context of scientific and social controversy. METHODS: We included all adults who were admitted to one of the TBD-RC from 2017 to 2020. A telephone satisfaction survey was conducted 12 months after their first consultation. It consisted of 5 domains, including 2 free-text items: "What points did you enjoy?" and "What would you like us to change or to improve?". In the current study, the 2 free-items were analyzed with a qualitative method called reflexive thematic analysis within a semantic and latent approach. RESULTS: The answer rate was 61.3% (349/569) and 97 distinctive codes from the 2-free-text items were identified and classified into five themes: (1) multidisciplinarity makes it possible to set up quality time dedicated to patients; (2) multidisciplinarity enables seamless carepaths despite the public hospital crisis compounded by the COVID-19 pandemic; (3) multidisciplinarity is defined as trust in the team's competences; (4) an ambivalent opinion and uncertainty are barriers to acceptance of the diagnosis, reflecting the strong influence of the controversy around LB; and (5) a lack of adapted communication about TBDs, their management, and ongoing research is present. CONCLUSION: The multidisciplinary management for suspected LB seemed an answer to medical wandering for the majority of patients and helped avoid misinformation, enabling better patient-centered shared information and satisfaction, despite the context of controversy.

Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications.

BACKGROUND: Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms. METHODS: We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients-divided into a discovery and validation cohort-were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments. RESULTS: We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses. CONCLUSIONS: Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures. TRIAL REGISTRATION: The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015-02-13).

Through the Eyes of Uncertainty: Giant Cell Arteritis and Lyme Neuroborreliosis in a Story of Vision Loss.

Acute vision loss is a prevalent clinical manifestation associated with a broad spectrum of differential diagnoses, encompassing demyelinating diseases, neoplastic processes, autoimmune disorders, and infectious conditions. A rare but noteworthy infectious etiology contributing to acute vision loss is neurological Lyme disease (Lyme neuroborreliosis)-induced optic neuritis. Lyme disease, a vector-borne illness caused by the spirochete Borrelia burgdorferi, has the potential to affect multiple physiological systems and unfolds in three distinct stages. Another significant contributor to acute vision loss is giant cell arteritis, an autoimmune vasculitis that commonly affects large- and medium-sized vessels, including the temporal and ophthalmic arteries. This relatively common condition may manifest with symptoms, such as jaw claudication, headaches, and visual disturbances. The precise identification of the underlying cause of acute visual loss is of utmost importance for physicians, as it is instrumental in averting undesirable complications. An 80-year-old female presents to the emergency room with a sudden onset of blurry vision of the left eye, right-sided weakness, dysarthria, jaw pain, headache, and left facial droop. Following consultations with rheumatology and ophthalmology specialists, giant cell arteritis emerged as a primary consideration in the differential diagnosis for the observed vision loss. Subsequently, a temporal artery biopsy was conducted, definitively confirming the diagnosis of giant cell arteritis. Considering the patient's residence in an area endemic to Lyme disease, a Lyme immunoglobulin G (IgG) titer was ordered. The results returned positive, suggesting the presence of Lyme neuroborreliosis.

Lyme disease and Whipple's disease: a comprehensive review for the rheumatologist.

Despite their rarity, Lyme disease and Whipple's disease are of significant importance in rheumatology, as both can manifest as chronic arthritis, presenting challenges in the differential diagnosis of inflammatory arthropathies. In Lyme disease, arthritis typically emerges as a late manifestation, usually occurring six months after the onset of erythema migrans. The predominant presentation involves mono- or oligoarthritis of large joints, with a chronic or remitting-recurrent course. Even with appropriate antimicrobial treatment, arthritis may persist due to inadequate immunological control triggered by the disease. In contrast, Whipple's disease may present with a migratory and intermittent seronegative poly- or oligoarthritis of large joints, preceding classic gastrointestinal symptoms by several years. Both disorders, particularly Whipple's disease, can be misdiagnosed as more common autoimmune rheumatic conditions such as rheumatoid arthritis and spondyloarthritis. Epidemiology is crucial in suspecting and diagnosing Lyme disease, as the condition is transmitted by ticks prevalent in specific areas of the United States, Europe, and Asia. On the contrary, the causative agent of Whipple's disease is widespread in the environment, yet invasive disease is rare and likely dependent on host genetic factors. In addition to erythema migrans in Lyme disease and gastrointestinal manifestations in Whipple's disease, neurological and cardiac involvement can further complicate the course of both. This article offers a comprehensive review of the epidemiological, pathophysiological, clinical, and therapeutic aspects of both diseases.

Incidence of Lyme Borreliosis in Germany: A retrospective observational healthcare claims study.

Lyme borreliosis (LB) is the most common tick-borne disease in Germany. Although the incidence of LB in Germany has been assessed in several studies, those studies either used data from statutory surveillance, which frequently underreport cases, or data from health claims databases, which may overestimate cases due to non-specific LB case definitions. Here, using a more specific case definition, we describe the incidence of medically-attended LB by disease manifestation, age group, and federal state for the period 2015-2019. Both inpatient and outpatient cases were analyzed from a claims database. To be eligible for inclusion, patients were required to have an LB specific ICD-10 GM diagnosis code plus an antibiotic prescription, and for disseminated manifestations, a laboratory test order additionally. LB cases were classified as erythema migrans (EM), or disseminated disease including Lyme arthritis (LA), Lyme neuroborreliosis (LNB), and all other disease manifestations (OTH). Between 2015 and 2019, the incidence of medically-attended LB cases ranged from 195.7/100,000 population per year (95% confidence interval [CI], 191.0 - 200.5) to 254.5/100,000 population per year (95% CI, 249.0 - 260.0) per year. The majority of cases (92.2%) were EM, while 2.8% presented as LA, 3.8% as LNB, and 1.2% as OTH. For both EM and disseminated disease, the incidence peaked in children aged 5-9 years and in older adults. By federal state, the incidence of medically-attended EM ranged from 74.4/100,000 population per year (95% CI, 71.9 - 77.0) per year in Hamburg, to 394.1/100,000 population per year (95% CI, 370.7 - 417.6) per year in Saxony, whereas for medically-attended disseminated disease, the highest incidence was in Thuringia, Saxony, and Bavaria (range: 22.0 [95% CI, 19.9 - 24.0] to 35.7 [95% CI, 34.7 - 36.7] per 100,000 population per year). This study comprehensively estimated the incidence of all manifestations of medically-attended LB and showed a high incidence of LB throughout Germany. Results from the study support performing epidemiological studies in all federal states to measure the burden of LB and to invest in public health interventions for prevention.

Incidence of Lyme Carditis and Lyme Carditis as a Cause of Pacemaker Implantation: A Nationwide Registry-Based Case-Control Study.

Background: Lyme borreliosis (LB) of the heart is called Lyme carditis (LC), which often manifests with high-grade atrioventricular block (AVB) requiring pacemaker implantation. LC is treated with antibiotics, and most patients recover fully after treatment. The overall incidence of LC, and of LC as a cause of pacemaker implantation, has not previously been systematically studied. Methods: This was a case-control study based on data from Swedish national registers. The study was divided into two parts; part 1 including all patients diagnosed with AVB between 2001 and 2018, and part 2 including all patients who had received a pacemaker due to AVB between 2010 and 2018. Patients diagnosed with LB 90 days before and 180 days after the AVB diagnosis were identified among the patients and compared to matched control groups generated from the general population. Results: Of 81 063 patients with AVB, 102 were diagnosed with LB. In the control group, 27 were diagnosed with LB. The yearly incidence of LC was 0.056 per 100 000 adults and year. Of 25 241 patients who had received a pacemaker for AVB, 31 were diagnosed with LB. In the control group, 8 were diagnosed with LB. The yearly incidence of LC as a cause of pacemaker implantation was 0.033 per 100 000 adults and year. The estimated risk for patients with LC to receive a permanent pacemaker was 59%. Conclusions: LC is a rare cause of AVB. Nevertheless, more than half of patients with LC receive a permanent pacemaker for a condition that is easily cured with antibiotics.

Discrepancy between IDSA and ESGBOR in Lyme disease: Individual participant meta-analysis in Türkiye.

BACKGROUND: The evidence on the prevalence of Lyme borreliosis (LB) is limited, but there is a suspicion of overdiagnosis of LB in recent years. We reviewed the LB diagnosis and treatment-related data in Türkiye, based on the Infectious Diseases Society of America (IDSA) 2020 and European Society of Clinical Microbiology and Infectious Diseases Study Group for Lyme Borreliosis (ESGBOR) 2018 guidelines. By detecting the disagreements between these two, we outlined the areas to be improved for future guidelines. METHODS: We performed a literature search according to the PRISMA guidelines in PubMed, Ovid-Medline, Web of Science, Turkish Medline, Scopus, CINAHL, ULAKBIM TR Index, Google Scholar and Cochrane Library databases. We included the published cases in a database and evaluated according to IDSA and ESGBOR guidelines. We outlined the reasons for misdiagnoses and inappropriate uses of antibiotics. RESULTS: We included 42 relevant studies with 84 LB cases reported from Türkiye between 1990 and December 2022. Among 84 cases, the most common clinical findings were nervous system findings (n = 37, 44.0%), erythema migrans (n = 29, 34.5%) and ophthalmologic findings (n = 15, 17.9%). The IDSA 2020 and ESGBOR 2018 guidelines agreed on the diagnosis of 71 (84.5%) cases; there was an agreement that 31 cases (36.9%) were misdiagnosed and 40 cases (47.6%) were correctly diagnosed, and there was disagreement for 13 cases (15.5%). Serum immunoglobulin M (IgM), IgG measurements by ELISA and western blot were widely performed, and they were effective in definitive diagnosis merely when used according to guidelines. Inappropriate use of antibiotics was detected in 42 (50.0%) of cases which were classified in the following categories: incorrect LB diagnosis, inappropriate choice of antibiotic, inappropriate route of drug administration and prolonged antibiotic treatment. CONCLUSION: Overdiagnosis and non-adherence to guidelines is a common problem. The discordance between seroprevalence and clinical studies necessitates a consensus over the best clinical approach.

Why Is the Duration of Erythema Migrans at Diagnosis Longer in Patients with Lyme Neuroborreliosis Than in Those without Neurologic Involvement?

In prior studies, the skin lesion erythema migrans (EM) was present for a longer time period before diagnosis of concomitant borrelial meningoradiculoneuritis (Bannwarth's syndrome) compared to EM patients without neurologic symptoms. To determine if this observation pertains to other manifestations of Lyme neuroborreliosis (LNB), we compared EM characteristics in patients with borrelial meningoradiculoneuritis (n = 122) to those with aseptic meningitis without radicular pain (n = 72 patients), and to patients with EM but without neurologic involvement (n = 12,384). We also assessed factors that might impact duration. We found that the duration of EM at diagnosis in patients with borrelial meningoradiculoneuritis was not significantly different compared with those with LNB without radicular pain (34 vs. 26 days; p = 0.227). The duration of EM for each of these clinical presentations of LNB, however, was significantly longer than in patients with EM without LNB (10 days; p < 0.001). Contributing factors to this difference might have been that patients with LNB failed to recognize that they had EM or were unaware of the importance of not delaying antibiotic treatment for EM. In conclusion, the duration of the EM skin lesion in EM patients with LNB is longer than in patients with just EM, irrespective of the type of LNB.

Purification of Borrelia burgdorferi Outer Membrane Vesicles.

Bacterial outer membrane vesicles (OMVs) are spherical membrane constructs shed by gram-negative bacteria. OMVs produced by the Lyme disease pathogen Borrelia burgdorferi have been identified to contain such virulence factors as OspA, OspB, OspC, and genetic material. However, the function and possible pathogenicity of borrelial OMVs are still undetermined. Therefore, further research on borrelial OMVs is required, and for that a standard method for OMV purification is necessary. Here we describe a successful and reproducible purification of borrelial outer membrane vesicles using concentration, filtration, and ultracentrifugation steps.

Coinfection of Babesia and Borrelia in the Tick Ixodes ricinus-A Neglected Public Health Issue in Europe?

Ixodes ricinus nymphs and adults removed from humans, and larvae and nymphs from birds, have been analysed for infection with Babesia species and Borrelia species previously in separately published studies. Here, we use the same data set to explore the coinfection pattern of Babesia and Borrelia species in the ticks. We also provide an overview of the ecology and potential public health importance in Sweden of I. ricinus infected both with zoonotic Babesia and Borrelia species. Among 1952 nymphs and adult ticks removed from humans, 3.1% were PCR-positive for Babesia spp. Of these Babesia-positive ticks, 43% were simultaneously Borrelia-positive. Among 1046 immatures of I. ricinus removed from birds, 2.5% were Babesia-positive, of which 38% were coinfected with Borrelia species. This study shows that in I. ricinus infesting humans or birds in Sweden, potentially zoonotic Babesia protozoa sometimes co-occur with human-pathogenic Borrelia spp. Diagnostic tests for Babesia spp. infection are rarely performed in Europe, and the medical significance of this pathogen in Europe could be underestimated.

Microbiologic Findings in a Cohort of Patients with Erythema Migrans.

Erythema migrans (EM) is the initial and the most frequent clinical manifestation of Lyme borreliosis (LB). Herein, we report on the capacity of culture and serology for the demonstration of Borrelia infection in a cohort of 292 patients diagnosed with typical EM at a single medical center. The median duration of EM at diagnosis was 12 days, and the largest diameter was 16 cm; 252 (86.3%) patients presented with solitary EM, whereas 40 (13.7%) had multiple EM. A total of 95/292 (32.5%) patients had positive IgM, and 169 (57.9%) had positive IgG serum antibodies; the Borrelia isolation rate was 182/292 (62.3%). The most frequent species by far was B. afzelii (142/148, 95.9%) while B. garinii (2.7%) and B. burgdorferi s.s. (1.4%) were rare. IgM seropositivity was associated with a younger age, multiple EM and the absence of underlying chronic illness; IgG seropositivity was associated with the duration of EM at diagnosis, the diameter of the EM, having had a previous episode of LB and the absence of symptoms at the site of the EM. Furthermore, the Borrelia isolation rate was statistically significantly lower in patients with positive Borrelia IgM antibodies. Although microbiologic analyses are not needed for the diagnosis of typical EM, they enable insights into the etiology and dynamics of the immune response in the course of early LB.

Comparative Evaluation of the Efficacy of Two Ectoparasiticides in Preventing the Acquisition of Borrelia burgdorferi by Ixodes scapularis and Ixodes ricinus: A Canine Ex Vivo Model.

In dogs, tick infestation can cause damage ranging from a simple skin irritation to severe diseases and/or paralysis leading to animal death. For example, Ixodes ricinus and I. scapularis are among the tick species incriminated the most in the transmission of Borrelia burgdorferi, the agent of human and canine Lyme borreliosis (LB). In this study, we aimed to compare the efficacy of two products designed for dogs-an oral systemic ectoparasiticide and a topical repellent ectoparasiticide-against the acquisition of B. burgdorferi by adult I. scapularis and I. ricinus using an ex vivo model. Thirty-two beagle dogs were included in a parallel-group-designed, randomized, single-center, negative-controlled efficacy study. The dogs were allocated to three groups based on gender and body weight: a fluralaner (F, Bravecto®) treatment group (n = 8), administered a single oral treatment on day 0 at the recommended dose; a dinotefuran-permethrin-pyriproxyfen (DPP, Vectra® 3D) treatment group (n = 8), topically treated on day 56 at the recommended dose; and an untreated control group (n = 16). Blood and hair were collected from each dog on days 58, 63, 70, 77, and 84. Hair was added to the silicone-based membrane separating two glass chambers forming the feeding unit (FU). Chamber 1 was filled with blood spiked with B. burgdorferi sensu stricto, strain B31 (105 cells/mL). Chamber 2, glued below chamber 1, was seeded with 20 adult I. scapularis or I. ricinus. The FUs (n = 240) were incubated at 37 °C with a humidity >90%. Tick survival, attachment, and feces presence were observed from 1 h up to 72 h after tick seeding. The uptake of B. burgdorferi was determined in ticks using nested polymerase chain reaction (nPCR). The acaricidal efficacy of DPP-treated hair was 100% within 1 h of tick release on every study day for both I. ricinus and I. scapularis. The speed of kill associated with DPP was sufficiently fast to prevent tick attachment and engorgement, and, consequently, to prevent the acquisition of B. burgdorferi. In the F-treated group, the acaricidal efficacy observed at 12 h, throughout the study, was <20% and <28% for I. scapularis and I. ricinus, respectively. Furthermore, tick feces were observed in the FUs, and several female ticks (I. scapularis (n = 55) and I. ricinus (n = 94)) tested positive for B. burgdorferi. The results provide proof of concept for the use of an ex vivo model based on an artificial feeding system to compare two ectoparasiticides against the acquisition of B. burgdorferi by I. ricinus and I. scapularis. In addition, our results demonstrate the superiority of DPP compared to F in the speed of acaricidal activity against ticks, as well as in preventing the acquisition of B. burgdorferi.

Male C57BL/6J mice have higher presence and abundance of Borrelia burgdorferi in their ventral skin compared to female mice.

Borrelia burgdorferi is a tick-borne spirochete that causes Lyme disease in humans. The host immune system controls the abundance of the spirochete in the host tissues. Recent work with immunocompetent Mus musculus mice strain C3H/HeJ found that males had a higher tissue infection prevalence and spirochete load compared to females. The purpose of this study was to determine whether host sex and acquired immunity interact to influence the prevalence and abundance of spirochetes in the tissues of the commonly used mouse strain C57BL/6. Wildtype (WT) mice and their SCID counterparts (C57BL/6) were experimentally infected with B. burgdorferi via tick bite. Ear biopsies were sampled at weeks 4, 8, and 12 post-infection (PI) and five tissues (left ear, ventral skin, heart, tibiotarsal joint of left hind leg, and liver) were collected at necropsy (16 weeks PI). The mean spirochete load in the tissues of the SCID mice was 260.4x higher compared to the WT mice. In WT mice, the infection prevalence in the ventral skin was significantly higher in males (40.0 %) compared to females (0.0 %), and the spirochete load in the rear tibiotarsal joint was significantly higher (4.3x) in males compared to females. In SCID mice, the spirochete load in the ventral skin was 200.0x higher in males compared to females, but there were no significant sex-specific difference in spirochete load in the other tissues (left ear, heart, tibiotarsal joint, or liver). Thus, the absence of acquired immunity greatly amplified the spirochete load in the ventral skin of male mice. It is important to note that the observed sex-specific differences in laboratory mice cannot be extrapolated to humans. Future studies should investigate the mechanisms underlying the male bias in the abundance of B. burgdorferi in the mouse skin.

Spatial multi-criteria decision analysis for the selection of sentinel regions in tick-borne disease surveillance.

BACKGROUND: The implementation of cost-effective surveillance systems is essential for tracking the emerging risk of tick-borne diseases. In Canada, where Lyme disease is a growing public health concern, a national sentinel surveillance network was designed to follow the epidemiological portrait of this tick-borne disease across the country. The surveillance network consists of sentinel regions, with active drag sampling carried out annually in all regions to assess the density of Ixodes spp. ticks and prevalence of various tick-borne pathogens in the tick population. The aim of the present study was to prioritize sentinel regions by integrating different spatial criteria relevant to the surveillance goals. METHODS: We used spatially-explicit multi-criteria decision analyses (MCDA) to map priority areas for surveillance across Canada, and to evaluate different scenarios using sensitivity analyses. Results were shared with stakeholders to support their decision making for the selection of priority areas to survey during active surveillance activities. RESULTS: Weights attributed to criteria by decision-makers were overall consistent. Sensitivity analyses showed that the population criterion had the most impact on rankings. Thirty-seven sentinel regions were identified across Canada using this systematic and transparent approach. CONCLUSION: This novel application of spatial MCDA to surveillance network design favors inclusivity of nationwide partners. We propose that such an approach can support the standardized planning of spatial design of sentinel surveillance not only for vector-borne disease BDs, but more broadly for infectious disease surveillance where spatial design is an important component.

Costs associated with informal health care pathway for patients with suspected Lyme borreliosis.

OBJECTIVES: To compare the direct and indirect medical costs for patients with suspected Lyme borreliosis according to whether or not they had used an informal care pathway. PATIENTS AND METHODS: We retraced the care pathways of participating patients by a prospective questionnaire survey and a retrospective analysis of care records. Direct and indirect costs were estimated using a micro-costing method from different perspectives. We compared the costs of patients who had consulted a "Lyme Doctor" (informal care pathway) with those who had only used the formal care pathway. Non-parametric tests were appraised the significance of the differences between the two groups of patients. RESULTS: Out of 103 eligible patients, 49 (including 12 having used an informal health care pathway) agreed to be investigated. Five expenditure items entirely borne by patients were significantly higher for patients following an informal care pathway: productivity loss (3041 ± 6580 vs 194 ± 1177 euros, p = 0.01), alternative therapies (3484 ± 7308 vs 369 ± 956 euros), biological tests sent abroad (571 ± 1415 vs 17 ± 92 euros, p < 0.01), self-medication (918 ± 1998 vs 133 ± 689, p = 0.02) and transport (3 094 ± 3456 vs 1 123 ± 1903p = 0.01). CONCLUSIONS: From the patient's standpoint, the informal care pathway involving consultation with a Lyme Doctor is far more expensive than the formal care pathway. More specifically, the patient has to bear the costs of alternative treatments and repeated, non-recommended examinations.

Lyme borreliosis in pediatric population: Clinical, diagnostic and therapeutic features.

INTRODUCTION: Lyme borreliosis (LB) in the paediatric population is an understudied entity with certain peculiarities. The objective of this study is to describe the characteristics of paediatric patients with LB, and their diagnostic and therapeutic processes. METHODS: Descriptive and retrospective study in patients up to 14 years old with suspected or confirmed LB between 2015 and 2021. RESULTS: A total of 21 patients were studied: 18 with confirmed LB (50% women; median age 6.4 years old) and 3 false positive of the serology. Clinical features in the 18 patients with LB were: neurological (3, neck stiffness; 6, facial nerve palsy), dermatological (6, erythema migratory), articular (1), and non-specific manifestations (5). Serological diagnosis was confirmatory in 83.3% of cases. A total of 94.4% patients received antimicrobial treatment (median duration, 21 days). All recovered with resolution of symptoms. CONCLUSIONS: LB diagnosis is difficult in the paediatric population and presents clinical and therapeutic peculiarities, with favourable prognosis.

Structure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric form.

ATP-dependent proteases FtsH are conserved in bacteria, mitochondria, and chloroplasts, where they play an essential role in degradation of misfolded/unneeded membrane and cytosolic proteins. It has also been demonstrated that the FtsH homologous protein BB0789 is crucial for mouse and tick infectivity and in vitro growth of the Lyme disease-causing agent Borrelia burgdorferi. This is not surprising, considering B. burgdorferi complex life cycle, residing in both in mammals and ticks, which requires a wide range of membrane proteins and short-lived cytosolic regulatory proteins to invade and persist in the host organism. In the current study, we have solved the crystal structure of the cytosolic BB0789166-614, lacking both N-terminal transmembrane α-helices and the small periplasmic domain. The structure revealed the arrangement of the AAA+ ATPase and the zinc-dependent metalloprotease domains in a hexamer ring, which is essential for ATPase and proteolytic activity. The AAA+ domain was found in an ADP-bound state, while the protease domain showed coordination of a zinc ion by two histidine residues and one aspartic acid residue. The loop region that forms the central pore in the oligomer was poorly defined in the crystal structure and therefore predicted by AlphaFold to complement the missing structural details, providing a complete picture of the functionally relevant hexameric form of BB0789. We confirmed that BB0789 is functionally active, possessing both protease and ATPase activities, thus providing novel structural-functional insights into the protein, which is known to be absolutely necessary for B. burgdorferi to survive and cause Lyme disease.

Structural studies of chromosomally encoded outer surface lipoprotein BB0158 from Borrelia burgdorferi sensu stricto.

Lyme disease, or also known as Lyme borreliosis, is caused by the spirochetes belonging to the Borrelia burgdorferi sensu lato complex, which can enter the human body following the bite of an infected tick. Many membrane lipid-bound proteins, also known as lipoproteins, are located on the surface of B. burgdorferi sensu lato and play a crucial role in the spirochete to interact with its environment, whether in ticks or mammals. Since the spirochete needs to perform various tasks, such as resisting the host's immune system or spreading throughout the organism, it is not surprising that numerous surface proteins have been found to be essential for B. burgdorferi sensu lato complex bacteria in causing Lyme disease. In this study, we have determined (at 2.4 Å resolution) and characterized the 3D structure of BB0158, one of the few chromosomally encoded outer surface proteins from B. burgdorferi sensu stricto. BB0158 belongs to the paralogous gene family 44 (PFam44), consisting of four other members (BB0159, BBA04, BBE09 and BBK52). The characterization of BB0158, which appears to form a domain-swapped dimer, in conjunction with the characterization of the corresponding PFam44 members, certainly contribute to our understanding of B. burgdorferi sensu stricto proteins.

Facial Paralysis Due to Brazilian Lyme Disease: A Case Report and Literature Review.

Lyme disease (LD) is a highly prevalent infection in the northern hemisphere, with an estimated incidence of 450,000 new annual cases in the United States and 65,000 new annual cases in Europe. Transmitted by the bite of a tick contaminated with a spirochete, the disease has three distinct stages. In the second phase of the disease, there may be neurological impairment, and the involvement of cranial nerve pairs occurs in this phase. Neuropathy of the seventh cranial nerve can occur in around 10% of adults with neurological involvement by Borrelia; in children, this incidence can reach 50%. A 32-year-old female patient presented with an abrupt facial paralysis that evolved into a difficult-to-resolve condition. With the appearance of probable contralateral involvement, LD was diagnosed. After the established treatment, the patient presented a good evolution of the symptoms.