Isolation and molecular characterization of a novel relapsing fever group Borrelia from the white-eared opossum Didelphis albiventris in Brazil.

This study aimed to detect, isolate and to characterize by molecular methods a relapsing fever group (RFG) Borrelia in white-eared opossums (Didelphis albiventris) from Brazil. During 2015-2018, when opossums (Didelphis spp.) were captured in six municipalities of the state of São Paulo, Brazil, molecular analyses revealed the presence of a novel RFG Borrelia sp. in the blood of seven opossums (Didelphis albiventris), out of 142 sampled opossums (4.9% infection rate). All seven infected opossums were from a single location (Ribeirão Preto municipality). In a subsequent field study in Ribeirão Preto during 2021, two new opossums (D. albiventris) were captured, of which one contained borrelial DNA in its blood. Macerated tissues from this infected opossum were inoculated into laboratory animals (rodents and rabbits) and two big-eared opossums (Didelphis aurita), which had blood samples examined daily via dark-field microscopy. No spirochetes were visualized in the blood of the laboratory animals. Contrastingly, spirochetes were visualized in the blood of the two D. aurita opossums between 12 and 25 days after inoculation. Blood samples from these opossums were used for a multi-locus sequencing typing (MLST) based on six borrelial loci. Phylogenies inferred from MLST genes positioned the sequenced Borrelia genotype into the RFG borreliae clade basally to borreliae of the Asian-African group, forming a monophyletic group with another Brazilian isolate, "Candidatus B. caatinga". Based on this concatenated phylogenetic analysis, which supports that the new borrelial isolate corresponds to a putative new species, we propose the name "Candidatus Borrelia mimona".

Lizards and the enzootic cycle of Borrelia burgdorferi sensu lato.

Emerging and re-emerging pathogens often stem from zoonotic origins, cycling between humans and animals, and are frequently vectored and maintained by hematophagous arthropod vectors. The efficiency by which these disease agents are successfully transmitted between vertebrate hosts is influenced by many factors, including the host on which a vector feeds. The Lyme disease bacterium Borrelia burgdorferi sensu lato has adapted to survive in complex host environments, vectored by Ixodes ticks, and maintained in multiple vertebrate hosts. The versatility of Lyme borreliae in disparate host milieus is a compelling platform to investigate mechanisms dictating pathogen transmission through complex networks of vertebrates and ticks. Squamata, one of the most diverse clade of extant reptiles, is comprised primarily of lizards, many of which are readily fed upon by Ixodes ticks. Yet, lizards are one of the least studied taxa at risk of contributing to the transmission and life cycle maintenance of Lyme borreliae. In this review, we summarize the current evidence, spanning from field surveillance to laboratory infection studies, supporting their contributions to Lyme borreliae circulation. We also summarize the current understanding of divergent lizard immune responses that may explain the underlying molecular mechanisms to confer Lyme spirochete survival in vertebrate hosts. This review offers a critical perspective on potential enzootic cycles existing between lizard-tick-Borrelia interactions and highlights the importance of an eco-immunology lens for zoonotic pathogen transmission studies.

Multifunctional interaction of CihC/FbpC orthologs of relapsing fever spirochetes with host-derived proteins involved in adhesion, fibrinolysis, and complement evasion.

Introduction: Relapsing fever (RF) remains a neglected human disease that is caused by a number of diverse pathogenic Borrelia (B.) species. Characterized by high cell densities in human blood, relapsing fever spirochetes have developed plentiful strategies to avoid recognition by the host defense mechanisms. In this scenario, spirochetal lipoproteins exhibiting multifunctional binding properties in the interaction with host-derived molecules are known to play a key role in adhesion, fibrinolysis and complement activation. Methods: Binding of CihC/FbpC orthologs to different human proteins and conversion of protein-bound plasminogen to proteolytic active plasmin were examined by ELISA. To analyze the inhibitory capacity of CihC/FbpC orthologs on complement activation, a microtiter-based approach was performed. Finally, AlphaFold predictions were utilized to identified the complement-interacting residues. Results and discussion: Here, we elucidate the binding properties of CihC/FbpC-orthologs from distinct RF spirochetes including B. parkeri, B. hermsii, B. turicatae, and B. recurrentis to human fibronectin, plasminogen, and complement component C1r. All CihC/FbpC-orthologs displayed similar binding properties to fibronectin, plasminogen, and C1r, respectively. Functional studies revealed a dose dependent binding of plasminogen to all borrelial proteins and conversion to active plasmin. The proteolytic activity of plasmin was almost completely abrogated by tranexamic acid, indicating that lysine residues are involved in the interaction with this serine protease. In addition, a strong inactivation capacity toward the classical pathway could be demonstrated for the wild-type CihC/FbpC-orthologs as well as for the C-terminal CihC fragment of B. recurrentis. Pre-incubation of human serum with borrelial molecules except CihC/FbpC variants lacking the C-terminal region protected serum-susceptible Borrelia cells from complement-mediated lysis. Utilizing AlphaFold2 predictions and existing crystal structures, we mapped the putative key residues involved in C1r binding on the CihC/FbpC orthologs attempting to explain the relatively small differences in C1r binding affinity despite the substitutions of key residues. Collectively, our data advance the understanding of the multiple binding properties of structural and functional highly similar molecules of relapsing fever spirochetes proposed to be involved in pathogenesis and virulence.

First molecular detection of Borrelia sp. in tapirs (Tapirus terrestris).

Borrelia theileri is a tick-borne spirochete causative agent of fever, apathy and reduced food consumption in cattle. Molecular diagnosis has expanded the understanding of Borrelia theileri with new hosts and geographical locations being described. The present study aimed to describe the first molecular detection of B. theileri in wild tapirs (Tapirus terrestris) from South America. Blood DNA samples obtained from 99 tapirs sampled in Pantanal (n = 61) and Cerrado (n = 38) biomes were screened using a qPCR assay based on the 16 S rRNA gene of Borrelia sp. Positive samples in the qPCR assay were subjected to PCR assays to allow characterization of fragments from 16 S rRNA and flaB genes. Two (2/99; 2.0%) animals from Pantanal biome were positive in the qPCR and one sample presented bands of expected size for the flaB protocol. Amplicons from this sample were successfully cloned and sequenced. In the phylogenetic analysis, Borrelia sp. from T. terrestris grouped together with B. theileri sequences previously detected in Rhipicephalus microplus ticks and cattle from Minas Gerais State in Brazil, Rhipicephalus geigyi from Mali, and R. microplus and Haemaphysalis sulcata from Pakistan. This finding contributes to our knowledge regarding susceptible hosts species for B. theileri. More studies are necessary to understand the potential effects of B. theileri on tapir's health.

Unprecedented genetic variability of PFam54 paralogs among Eurasian Lyme borreliosis-causing spirochetes.

Lyme borreliosis (LB) is the most common vector-borne disease in the Northern Hemisphere caused by spirochetes belonging to the Borrelia burgdorferi sensu lato (Bbsl) complex. Borrelia spirochetes circulate in obligatory transmission cycles between tick vectors and different vertebrate hosts. To successfully complete this complex transmission cycle, Bbsl encodes for an arsenal of proteins including the PFam54 protein family with known, or proposed, influences to reservoir host and/or vector adaptation. Even so, only fragmentary information is available regarding the naturally occurring level of variation in the PFam54 gene array especially in relation to Eurasian-distributed species. Utilizing whole genome data from isolates (n = 141) originated from three major LB-causing Borrelia species across Eurasia (B. afzelii, B. bavariensis, and B. garinii), we aimed to characterize the diversity of the PFam54 gene array in these isolates to facilitate understanding the evolution of PFam54 paralogs on an intra- and interspecies level. We found an extraordinarily high level of variation in the PFam54 gene array with 39 PFam54 paralogs belonging to 23 orthologous groups including five novel paralogs. Even so, the gene array appears to have remained fairly stable over the evolutionary history of the studied Borrelia species. Interestingly, genes outside Clade IV, which contains genes encoding for proteins associated with Borrelia pathogenesis, more frequently displayed signatures of diversifying selection between clades that differ in hypothesized vector or host species. This could suggest that non-Clade IV paralogs play a more important role in host and/or vector adaptation than previously expected, which would require future lab-based studies to validate.

Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

It's not all about flagella - sticky invasion by pathogenic spirochetes.

Pathogenic spirochetes cause a range of serious human diseases such as Lyme disease (LD), syphilis, leptospirosis, relapsing fever (RF), and periodontal disease. Motility is a critical virulence factor for spirochetes. From the mechanical perspective of the infection, it has been widely believed that flagella are the sole key players governing the migration and dissemination of these pathogens in the host. Here, we highlight the important contribution of spirochetal surface-exposed adhesive molecules and their dynamic interactions with host molecules in the process of infection, specifically in spirochetal swimming and crawling migration. We believe that these recent findings overturn the prevailing view depicting the spirochetal body to be just an inert elastic bag, which does not affect spirochetal cell locomotion.

Serological evidence of louse-borne relapsing fever in northern Kenya.

BACKGROUND: Tick- and louse-borne relapsing fever are highly-neglected, vector-borne diseases caused by diverse Borrelia species. Presently, there are no data available on the endemicity of tick- and louse-borne relapsing fever spirochetes in Kenya. Here, we present data of a retrospective study on the seroprevalence of louse-borne relapsing fever (LBRF) in northern Kenya. METHODS: A novel immunoassay, recently established for the diagnosis of LBRF was utilized to screen 2005 blood samples collected from individuals with fever without a source in Turkana County, Kenya between May 2009 and November 2010 for anti-LBRF antibodies. RESULTS: Out of the 2005 sera analyzed, 287 samples (14.3 %) were considered anti-LBRF IgG positive. Subsequent analyses revealed that 87 out of 152 sera randomly selected from these 2005 samples were tested positive (57.2 %) for anti-LBRF IgM antibodies. Most of the IgG and IgM positive samples were from individuals living in northern regions of Turkana County. CONCLUSION: Our serological finding provides strong evidence for the occurrence of LBRF in Kenya.

Borrelia burgdorferi colonizes the mammary glands of lactating C3H mice: does not cause congenital Lyme disease.

Transplacental transmission of syphilis causing spirochete, Treponema pallidum subspecies pallidum, from mother to child results in congenital syphilis, an ever-expanding devastating disease worldwide. Although adverse effects of untreated gestational Lyme disease, caused by a related spirochete, Borrelia burgdorferi on fetus viability and development have been observed, cases of congenital Lyme disease are not reported. In this study, we show that B. burgdorferi colonizes mammary glands of C3H mice only postpartum; however, neither transmission of these spirochetes from dams-to-pups occurs nor congenital Lyme disease is observed in pups.

High prevalence and genetic diversity of Treponema paraluisleporidarum isolates in European lagomorphs.

IMPORTANCE: Syphilis is an ancient disease of humans and lagomorphs caused by two distinct but genetically closely related bacteria (>98% sequence identity based on the whole genome) of the genus Treponema. While human syphilis is well studied, little is known about the disease in the lagomorph host. Yet, comparative studies are needed to understand mechanisms in host-pathogen coevolution in treponematoses. Importantly, Treponema paraluisleporidarum-infected hare populations provide ample opportunity to study the syphilis-causing pathogen in a naturally infected model population without antibiotic treatment, data that cannot be obtained from syphilis infection in humans. We provide data on genetic diversity and are able to highlight various types of repetitions in one of the two hypervariable regions at the tp0548 locus that have not been described in the human syphilis-causing sister bacterium Treponema pallidum subsp. pallidum.

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.

The transcriptomic response to cannabidiol of Treponema denticola, a phytocannabinoid-resistant periodontal pathogen.

AIM: The use of cannabis, which contains multiple antimicrobials, may be a risk factor for periodontitis. We hypothesized that multiple oral spirochetes would be phytocannabinoid-resistant and that cannabidiol (CBD) would act as an environmental stressor to which Treponema denticola would respond transcriptionally, thereby providing first insights into spirochetal survival strategies. MATERIALS AND METHODS: Oral spirochete growth was monitored spectrophotometrically in the presence and absence of physiologically relevant phytocannabinoid doses, the transcriptional response to phytocannabinoid exposure determined by RNAseq, specific gene activity fluxes verified using qRT-PCR and orthologues among fully sequenced oral spirochetes identified. RESULTS: Multiple strains of oral treponemes were resistant to CBD (0.1-10 µg/mL), while T. denticola ATCC 35405 was resistant to all phytocannabinoids tested (CBD, cannabinol [CBN], tetrahydrocannabinol [THC]). A total of 392 T. denticola ATCC 35405 genes were found to be CBD-responsive by RNAseq. A selected subset of these genes was independently verified by qRT-PCR. Genes found to be differentially activated by both methods included several involved in transcriptional regulation and toxin control. Suppressed genes included several involved in chemotaxis and proteolysis. CONCLUSIONS: Oral spirochetes, unlike some other periodontal bacteria, are resistant to physiological doses of phytocannabinoids. Investigation of CBD-induced transcriptomic changes provided insight into the resistance mechanisms of this important periodontal pathogen. These findings should be considered in the context of the reported enhanced susceptibility to periodontitis in cannabis users.

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.

Lysinoalanine cross-linking is a conserved post-translational modification in the spirochete flagellar hook.

Spirochetes cause Lyme disease, leptospirosis, syphilis, and several other human illnesses. Unlike other bacteria, spirochete flagella are enclosed within the periplasmic space where the filaments distort and push the cell body by the action of the flagellar motors. We previously demonstrated that the oral pathogen Treponema denticola (Td) and Lyme disease pathogen Borreliella burgdorferi (Bb) form covalent lysinoalanine (Lal) cross-links between conserved cysteine and lysine residues of the FlgE protein that composes the flagellar hook. In Td, Lal is unnecessary for hook assembly but is required for motility, presumably due to the stabilizing effect of the cross-link. Herein, we extend these findings to other, representative spirochete species across the phylum. We confirm the presence of Lal cross-linked peptides in recombinant and in vivo-derived samples from Treponema spp., Borreliella spp., Brachyspira spp., and Leptospira spp. As was observed with Td, a mutant strain of Bb unable to form the cross-link has greatly impaired motility. FlgE from Leptospira spp. does not conserve the Lal-forming cysteine residue which is instead substituted by serine. Nevertheless, Leptospira interrogans FlgE also forms Lal, with several different Lal isoforms being detected between Ser-179 and Lys-145, Lys-148, and Lys-166, thereby highlighting species or order-specific differences within the phylum. Our data reveal that the Lal cross-link is a conserved and necessary posttranslational modification across the spirochete phylum and may thus represent an effective target for the development of spirochete-specific antimicrobials.

Borrelia puertoricensis in opossums (Didelphis marsupialis) from Colombia.

BACKGROUND: The genus Borrelia comprises pathogenic species of bacteria that pose a significant risk to public health. Borrelia spp. are emerging or reemerging infectious agents worldwide with complex transmission cycles, and many species use rodents as vertebrate reservoir hosts. Spirochetes morphologically compatible with Borrelia have been recurrently observed in opossums; however, there is currently a lack of genetic evidence confirming infection or supporting that these marsupials are hosts of Borrelia spirochetes. METHODS: During 2017, 53 serum samples of Didelphis marsupialis from the municipality of Colosó (department of Sucre, Colombia) were collected and allocated in a serum bank. DNA extracted from the serum samples was submitted to a Borrelia genus-specific real-time PCR targeting the 16S rRNA gene. Positive samples were subsequently derived from semi-nested PCR protocols to obtain large fragments of the 16S rRNA and flaB genes. Obtained amplicons were subjected to Sanger sequencing. One positive sample was randomly selected for next-generation sequencing (NGS). Obtained reads were mapped to genomes of Borrelia spp. and sequences of two genes used in a multilocus sequence typing scheme retrieved for taxonomic assignment and phylogenetic analyses. RESULTS: Overall, 18.8% (10/53) of the samples were positive by qPCR. Of them, 80% (8/10) and 60% (6/10) were positive for the 16S rRNA and flaB genes after semi-nested PCRs, respectively. Bioinformatic analysis of one sample sequenced with NGS yielded 22 reads of genus Borrelia with different sizes. Two housekeeping genes, rplB and pyrG, were recovered. Nucleotide pairwise comparisons and phylogenetic analyses of 16S rRNA, flaB, rplB and pyrG genes showed that the Borrelia sp. found in opossums from Colosó corresponded to Borrelia puertoricensis. CONCLUSIONS: We describe the first molecular evidence to our knowledge of B. puertoricensis in Colombia, specifically in opossums, and the first detection of this spirochete in a vertebrate host since its isolation from Ornithodoros puertoricensis in Panama. This detection is also relevant because of the epidemiological importance of opossums as reservoirs of zoonotic diseases to humans.

Through the Eyes: A Case of Ocular Syphilis.

Syphilis is a bacterial disease caused by Treponema pallidum and is sexually transmitted via vaginal, anogenital, or orogenital contact. Vertical transmission between mother and unborn child is also possible, but transmission via skin-to-skin or blood contact is rare. The objective of this case is to highlight this rare ocular manifestation of syphilis as it manifests as a multisystemic disease affecting many organ systems. This is a case of a 46-year-old male with vision loss who was referred to the emergency department by an ophthalmologist. Two days before the presentation at the emergency department, the ophthalmologist observed the presence of optic disc edema in the left eye. At the emergency department, he complained of bright light spots in the left eye and complete darkness in the central aspect of the eyes. He reported having a non-pruritic erythematous rash on the anterior abdomen that began one week before his presentation at the emergency department. The patient also reported having multiple sexual partners. Physical examination findings showed a visual field defect in the left eye, normal bilateral eye movement, and a non-tender skin reticulation over the anterior abdominal wall. Lab results showed complete blood count (CBC) and comprehensive metabolic panel (CMP) within normal limits, fluorescent treponemal antibody (FTA) antibody reactive, human immunodeficiency virus (HIV) test and hepatitis panel negative, rapid plasma reagin (RPR) titer 1:64, and imaging results negative for any significant abnormalities. The infectious disease specialists were consulted, and the recommended IV penicillin of four million units every four hours was given. The patient reported an improvement in his blurry vision over three days. By six months, his vision was back to baseline. This case report is significant due to the rare occurrence of ocular complications as an initial presentation of syphilis. Considering the rising cases of syphilis in the United States, it is important to highlight the possibility of this uncommon clinical presentation of syphilis.

Molecular detection of Spirochetes and Borrelia burgdorferi in stray dogs of Nineveh province, Iraq.

Background: Borrelia burgdorferi is a Gram-negative bacterium that causes Lyme disease or borreliosis in domestic and wild animals, including dogs, with the possible transmission to humans. Aim: This study was conducted to investigate the infection rate of Spirochetes and B. burgdorferi in stray dogs in Nineveh province, Iraq. Methods: During the period from May to October (2022), a total of 55 stray dogs were selected randomly from different areas in Nineveh province, Iraq. Blood samples were collected from cephalic venous and tested molecularly using the conventional polymerase chain reaction technique. Results: The present study revealed that the total infection rates of Spirochetes and B. burgdorferi were 41.82% and 27.27%, respectively. Concerning age, values of infection rate, odds ratio, and relative risk of B. burgdorferi were increased significantly in dogs aged ? 4 months (42.86%, 3.505%, and 2.438%, respectively), while decreased in dogs of ? 1-3 (12.5%, 0.337% and 0.42%, respectively) and ? 3 (13.33%, 0.32% and 0.409%) years old when compared to dogs aged 5-12 months (27.27%, 1% and 1%, respectively). While concerning dogs sex, a significantly higher infection rate, odds ratio, and relative risk of B. burgdorferi were shown in females (32.56%, 5.495% and 6.792%, respectively) compared to males (8.33%, 0.182% and 0.147%, respectively). Conclusion: To the best of our knowledge, this represents the first Iraqi study on the prevalence of spirochetes, in particular B. burgdorferi, in stray dogs in Nineveh province (Iraq). However, additional studies of B. burgdorferi infection in other animals as well as vectors such as ticks in different geographic areas, appear necessary to detect variation in the distribution patterns of infection. In addition, owners and veterinarians should be aware of zoonotic diseases transmitted from wild and domestic animals, in particular those with tick-bite histories.

The In Vitro Antimicrobial Susceptibility of Borrelia burgdorferi sensu lato: Shedding Light on the Known Unknowns.

Human Lyme borreliosis (LB) represents a multisystem disorder that can progress in stages. The causative agents are transmitted by hard ticks of the Ixodes ricinus complex that have been infected with the spirochete Borrelia burgdorferi sensu lato. Today, LB is considered the most important human tick-borne illness in the Northern Hemisphere. The causative agent was identified and successfully isolated in 1982 and, shortly thereafter, antibiotic treatment was found to be safe and efficacious. Since then, various in vitro studies have been conducted in order to improve our knowledge of the activity of antimicrobial agents against B. burgdorferi s. l. The full spectrum of in vitro antibiotic susceptibility has still not been defined for some of the more recently developed compounds. Moreover, our current understanding of the in vitro interactions between B. burgdorferi s. l. and antimicrobial agents, and their possible mechanisms of resistance remains very limited and is largely based on in vitro susceptibility experiments on only a few isolates of Borrelia. Even less is known about the possible mechanisms of the in vitro persistence of spirochetes exposed to antimicrobial agents in the presence of human and animal cell lines. Only a relatively small number of laboratory studies and cell culture experiments have been conducted. This review summarizes what is and what is not known about the in vitro susceptibility of B. burgdorferi s. l. It aims to shed light on the known unknowns that continue to fuel current debates on possible treatment resistance and mechanisms of persistence of Lyme disease spirochetes in the presence of antimicrobial agents.

Autogenous reproduction by Ornithodoros turicata (Ixodida: Argasidae) females and vertical transmission of the tick-borne pathogen Borrelia turicatae (Spirochaetales: Borreliaceae).

IMPORTANCE: Previous research has implicated Ornithodoros ticks, including Ornithodoros turicata, as long-term reservoirs of relapsing fever (RF) spirochetes. Considering the tick's long lifespan and their efficiency in maintaining and transferring spirochetes within the population, the infection could persist in a given enzootic focus for decades. However, little is known about the relative importance of horizontal and vertical transmission routes in the persistence and evolution of RF Borrelia. Our observations on the reproductive biology of O. turicata in the absence of vertebrate hosts indicate an additional mechanism by which Borrelia turicatae can be maintained in the environment. This work establishes the foundation for studying O. turicata reproduction and spirochete-vector interactions, which will aid in devising control measures for Ornithodoros ticks and RF spirochetes.

Clinical and Pathologic Factors Associated With Colonic Spirochete (Brachyspira pilosicoli and Brachyspira aalborgi) Infection: A Comprehensive Systematic Review and Pooled Analysis.

OBJECTIVES: This study aims to determine what pathologic and clinical factors differentiate Brachyspira species that may be useful to clinicians and pathologists. METHODS: We identified 21 studies of Brachyspira infection with individual patient information (n = 113) and conducted a pooled analysis comparing each species. RESULTS: There were differences in the pathologic and clinical profiles of each Brachyspira species. Patients infected with Brachyspira pilosicoli infection were more likely to have diarrhea, fever, HIV, and immunocompromised conditions. Those patients infected with Brachyspira aalborgi were more likely to have lamina propria inflammation. CONCLUSIONS: Our novel data provide potential insights into the pathogenic mechanism(s) and the specific risk factor profile of Brachyspira species. This may be clinically useful when assessing and managing patients.