Infection with Borrelia burgdorferi often triggers pathophysiologic perturbations that are further augmented by the inflammatory responses of the host, resulting in the severe clinical conditions of Lyme disease. While our apprehension of the spatial and temporal integration of the virulence determinants during the enzootic cycle of B. burgdorferi is constantly being improved, there is still much to be discovered. Many of the novel virulence strategies discussed in this review are undetermined. Lyme disease spirochaetes must surmount numerous molecular and mechanical obstacles in order to establish a disseminated infection in a vertebrate host. These barriers include borrelial relocation from the midgut of the feeding tick to its body cavity and further to the salivary glands, deposition to the skin, haematogenous dissemination, extravasation from blood circulation system, evasion of the host immune responses, localization to protective niches, and establishment of local as well as distal infection in multiple tissues and organs. Here, the various well-defined but also possible novel strategies and virulence mechanisms used by B. burgdorferi to evade obstacles laid out by the tick vector and usually the mammalian host during colonization and infection are reviewed.

• Keywords
• Borrelia burgdorferi, Lyme disease, clinical manifestations, pathogenicity, tick-borne disease, virulence determinants,
• MeSH
• Borrelia burgdorferi * genetics   MeSH
• Virulence Factors MeSH
• Humans MeSH
• Lyme Disease * MeSH
• Mammals MeSH
• Virulence MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Virulence Factors MeSH

Transmission of the causative agents of numerous infectious diseases might be potentially conducted by various routes if this is supported by the genetics of the pathogen. Various transmission modes occur in related pathogens, reflecting a complex process that is specific for each particular host-pathogen system that relies on and is affected by pathogen and host genetics and ecology, ensuring the epidemiological spread of the pathogen. The recent dramatic rise in diagnosed cases of Lyme borreliosis might be due to several factors: the shifting of the distributional range of tick vectors caused by climate change; dispersal of infected ticks due to host animal migration; recent urbanization; an increasing overlap of humans' habitat with wildlife reservoirs and the environment of tick vectors of Borrelia; improvements in disease diagnosis; or establishment of adequate surveillance. The involvement of other bloodsucking arthropod vectors and/or other routes of transmission (human-to-human) of the causative agent of Lyme borreliosis, the spirochetes from the Borrelia burgdorferi sensu lato complex, has been speculated to be contributing to increased disease burden. It does not matter how controversial the idea of vector-free spirochete transmission might seem in the beginning. As long as evidence of sexual transmission of Borrelia burgdorferi both between vertebrate hosts and between tick vectors exists, this question must be addressed. In order to confirm or refute the existence of this phenomenon, which could have important implications for Lyme borreliosis epidemiology, the need of extensive research is obvious and required.

• Keywords
• Lyme borreliosis, sexually transmitted disease, spirochete, tick-borne disease,
• Publication type
• Journal Article MeSH

Lyme borreliosis is the most common zoonotic disease transmitted by ticks in Europe and North America. Despite having multiple tick vectors, the causative agent, Borrelia burgdorferisensu lato, is vectored mainly by Ixodes ricinus in Europe. In the present study, we aimed to review and summarize the existing data published from 2010 to 2016 concerning the prevalence of B. burgdorferi sensu lato spirochetes in questing I. ricinus ticks. The primary focus was to evaluate the infection rate of these bacteria in ticks, accounting for tick stage, adult tick gender, region, and detection method, as well as to investigate any changes in prevalence over time. The data obtained were compared to the findings of a previous metastudy. The literature search identified data from 23 countries, with 115,028 ticks, in total, inspected for infection with B. burgdorferi sensu lato We showed that the infection rate was significantly higher in adults than in nymphs and in females than in males. We found significant differences between European regions, with the highest infection rates in Central Europe. The most common genospecies were B. afzelii and B. garinii, despite a negative correlation of their prevalence rates. No statistically significant differences were found among the prevalence rates determined by conventional PCR, nested PCR, and real-time PCR.IMPORTANCEBorrelia burgdorferisensu lato is a pathogenic bacterium whose clinical manifestations are associated with Lyme borreliosis. This vector-borne disease is a major public health concern in Europe and North America and may lead to severe arthritic, cardiovascular, and neurological complications if left untreated. Although pathogen prevalence is considered an important predictor of infection risk, solitary isolated data have only limited value. Here we provide summarized information about the prevalence of B. burgdorferi sensu lato spirochetes among host-seeking Ixodes ricinus ticks, the principal tick vector of borreliae in Europe. We compare the new results with previously published data in order to evaluate any changing trends in tick infection.

• Keywords
• Borrelia burgdorferi sensu lato, Ixodes ricinus, Lyme borreliosis, Lyme disease, genospecies, meta-analysis, tick,
• MeSH
• Arachnid Vectors microbiology   MeSH
• Borrelia burgdorferi classification   genetics   isolation & purification   MeSH
• Ixodes microbiology   MeSH
• Humans MeSH
• Lyme Disease microbiology   transmission   MeSH
• Nymph microbiology   MeSH
• Prevalence MeSH
• Zoonoses microbiology   transmission   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

Determination of the causative agent of erythema-like skin lesions in case of nonspecific superficial perivascular dermatitis was supported by histological examination and led to the latter diagnosis of Hyperkeratosis lenticularis perstans (Flegel disease) in patient. The presence of antibodies against Borrelia burgdorferi in patient serum was confirmed by a routine ELISA method and verified by Western blot technique. Skin biopsy and blood specimens were analyzed by PCR and multilocus sequence analysis (MLSA). Western blot method revealed IgG antibody response against two specific antigens, 17 and 83 kDa proteins. The recombinant test detected IgG antibody response against p100 and p41 antigens. The sequence analysis of amplicons from the selected genomic loci obtained from skin biopsy and serum samples revealed the presence of two species from B. burgdorferi sensu lato complex as a co-infection in this patient-B. burgdorferi sensu stricto (s.s.) and Borrelia garinii.

• MeSH
• Antigens, Bacterial immunology   MeSH
• Biopsy MeSH
• Borrelia burgdorferi Group genetics   isolation & purification   MeSH
• Borrelia burgdorferi genetics   isolation & purification   MeSH
• DNA, Bacterial genetics   isolation & purification   MeSH
• Immunoglobulin G blood   MeSH
• Keratosis microbiology   pathology   MeSH
• Coinfection microbiology   pathology   MeSH
• Skin microbiology   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Multilocus Sequence Typing MeSH
• Polymerase Chain Reaction MeSH
• Antibodies, Bacterial blood   MeSH
• Blotting, Western MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• Antigens, Bacterial MeSH
• DNA, Bacterial MeSH
• Immunoglobulin G MeSH
• Antibodies, Bacterial MeSH

BACKGROUND: Out of 20 spirochete species from Borrelia burgdorferi sensu lato (s.l.) complex recognized to date some are considered to have a limited distribution, while others are worldwide dispersed. Among those are Borrelia burgdorferi sensu stricto (s.s.) and Borrelia bissettii which are distributed both in North America and in Europe. While B. burgdorferi s.s. is recognized as a cause of Lyme borreliosis worldwide, involvement of B. bissettii in human Lyme disease was not so definite yet. FINDINGS: Multilocus sequence typing of spirochete isolates originating from residents of Georgia and Florida, USA, revealed the presence of two Borrelia burgdorferi sensu stricto strains highly similar to those from endemic Lyme borreliosis regions of the northeastern United States, and an unusual strain that differed from any previously described in Europe or North America. Based on phylogenetic analysis of eight chromosomally located housekeeping genes divergent strain clustered between Borrelia bissettii and Borrelia carolinensis, two species from the B.burgdorferi s.l. complex, widely distributed among the multiple hosts and vector ticks in the southeastern United States. The genetic distance analysis showed a close relationship of the diverged strain to B. bissettii. CONCLUSIONS: Here, we present the analysis of the first North American human originated live spirochete strain that revealed close relatedness to B. bissettii. The potential of B. bissettii to cause human disease, even if it is infrequent, is of importance for clinicians due to the extensive range of its geographic distribution.

• MeSH
• Borrelia burgdorferi Group MeSH
• Borrelia burgdorferi MeSH
• Borrelia classification   genetics   isolation & purification   MeSH
• Genes, Essential MeSH
• Genotype MeSH
• Humans MeSH
• Lyme Disease diagnosis   microbiology   MeSH
• Molecular Sequence Data MeSH
• Multilocus Sequence Typing * MeSH
• Sequence Analysis, DNA MeSH
• Cluster Analysis MeSH
• Spirochaetales MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Florida MeSH
• Georgia MeSH

BACKGROUND: The controversy surrounding the potential impact of birds in spirochete transmission dynamics and their capacity to serve as a reservoir has existed for a long time. The majority of analyzed bird species are able to infect larval ticks with Borrelia. Dispersal of infected ticks due to bird migration is a key to the establishment of new foci of Lyme borreliosis. The dynamics of infection in birds supports the mixing of different species, the horizontal exchange of genetic information, and appearance of recombinant genotypes. METHODS: Four Borrelia burgdorferi sensu lato strains were cultured from Ixodes minor larvae and four strains were isolated from Ixodes minor nymphs collected from a single Carolina Wren (Thryothorus ludovicianus). A multilocus sequence analysis that included 16S rRNA, a 5S-23S intergenic spacer region, a 16S-23S internal transcribed spacer, flagellin, p66, and ospC separated 8 strains into 3 distinct groups. Additional multilocus sequence typing of 8 housekeeping genes, clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA was used to resolve the taxonomic status of bird-associated strains. RESULTS: Results of analysis of 14 genes confirmed that the level of divergence among strains is significantly higher than what would be expected for strains within a single species. The presence of cross-species recombination was revealed: Borrelia burgdorferi sensu stricto housekeeping gene nifS was incorporated into homologous locus of strain, previously assigned to B. americana. CONCLUSIONS: Genetically diverse Borrelia strains are often found within the same tick or same vertebrate host, presenting a wide opportunity for genetic exchange. We report the cross-species recombination that led to incorporation of a housekeeping gene from the B. burgdorferi sensu stricto strain into a homologous locus of another bird-associated strain. Our results support the hypothesis that recombination maintains a majority of sequence polymorphism within Borrelia populations because of the re-assortment of pre-existing sequence variants. Even if our findings of broad genetic diversity among 8 strains cultured from ticks that fed on a single bird could be the exception rather than the rule, they support the theory that the diversity and evolution of LB spirochetes is driven mainly by the host.

• MeSH
• Borrelia burgdorferi classification   genetics   isolation & purification   MeSH
• Genes, Essential MeSH
• Phylogeny MeSH
• Genetic Variation MeSH
• Ticks microbiology   MeSH
• Molecular Sequence Data MeSH
• Birds microbiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

Comparative analysis of ospC genes from 127 Borrelia burgdorferi sensu stricto strains collected in European and North American regions where Lyme disease is endemic and where it is not endemic revealed a close relatedness of geographically distinct populations. ospC alleles A, B, and L were detected on both continents in vectors and hosts, including humans. Six ospC alleles, A, B, L, Q, R, and V, were prevalent in Europe; 4 of them were detected in samples of human origin. Ten ospC alleles, A, B, D, E3, F, G, H, H3, I3, and M, were identified in the far-western United States. Four ospC alleles, B, G, H, and L, were abundant in the southeastern United States. Here we present the first expanded analysis of ospC alleles of B. burgdorferi strains from the southeastern United States with respect to their relatedness to strains from other North American and European localities. We demonstrate that ospC genotypes commonly associated with human Lyme disease in European and North American regions where the disease is endemic were detected in B. burgdorferi strains isolated from the non-human-biting tick Ixodes affinis and rodent hosts in the southeastern United States. We discovered that some ospC alleles previously known only from Europe are widely distributed in the southeastern United States, a finding that confirms the hypothesis of transoceanic migration of Borrelia species.

• MeSH
• Alleles * MeSH
• Antigens, Bacterial genetics   MeSH
• Borrelia burgdorferi genetics   isolation & purification   MeSH
• DNA, Bacterial chemistry   genetics   MeSH
• Genetic Variation MeSH
• Genotype MeSH
• Rodentia microbiology   MeSH
• Ixodes microbiology   MeSH
• Humans MeSH
• Molecular Sequence Data MeSH
• Bacterial Outer Membrane Proteins genetics   MeSH
• Sequence Analysis, DNA MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geographicals
• Europe MeSH
• North America MeSH
• Names of Substances
• Antigens, Bacterial MeSH
• DNA, Bacterial MeSH
• OspC protein MeSH Browser
• Bacterial Outer Membrane Proteins MeSH

This study presents the binding of ovine factor H (fH) by various serotypes of Borrelia and simultaneously correlates their complement resistance to sheep serum. Affinity ligand binding assay was employed to study the binding of borrelial proteins to ovine recombinant fH and its truncated forms (short consensus repeat, SCR 7 and SCRs 19-20). From a repertoire of 17 borrelial strains, only two strains showed affinity to sheep fH. A ~28-kDa protein of Borrelia burgdorferi sensu stricto (B. burgdorferi s.s., strain SKT-2) bound full-length fH as well as SCRs 19-20. This fH-binding protein was further identified as complement regulator-acquiring surface protein of B. burgdorferi (BbCRASP-1) by MALDI-TOF analysis. Surprisingly, a ~26-kDa protein of Borrelia bissettii (DN127) showed affinity to full-length fH but not to SCR 7 and SCRs19-20. In complement sensitivity assay, both strains-SKT-2 and DN127-were resistant to normal sheep serum. Significant complement resistance of two Borrelia garinii strains (G117 and T25) was also observed; however, none of those strains was able to bind sheep fH. Our study underscores the need of further exploration of fH-mediated evasion of complement system by Borrelia in domestic animals.

• MeSH
• Bacterial Proteins chemistry   genetics   immunology   MeSH
• Borrelia classification   genetics   immunology   isolation & purification   MeSH
• Kinetics MeSH
• Complement Factor H chemistry   immunology   MeSH
• Lyme Disease immunology   microbiology   veterinary   MeSH
• Molecular Sequence Data MeSH
• Sheep Diseases immunology   microbiology   MeSH
• Sheep MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Bacterial Proteins MeSH
• Complement Factor H MeSH

Borrelia burgdorferi sensu lato (s.l.) complex is a diverse group of worldwide distributed bacteria that includes 18 named spirochete species and a still not named group proposed as genomospecies 2. Descriptions of new species and variants continue to be recognized, so the current number of described species is probably not final. Most of known spirochete species are considered to have a limited distribution. Eleven species from the B. burgdorferi s.l. complex were identified in and strictly associated with Eurasia (B. afzelii, B. bavariensis, B. garinii, B. japonica, B. lusitaniae, B. sinica, B. spielmanii, B. tanukii, B. turdi, B. valaisiana, and B. yangtze), while another 5 (B. americana, B. andersonii, B. californiensis, B. carolinensis, and B. kurtenbachii) were previously believed to be restricted to the USA only. B. burgdorferi sensu stricto (s.s.), B. bissettii, and B. carolinensis share the distinction of being present in both the Old and the New World. Out of the 18 genospecies, 3 commonly and 4 occasionally infect humans, causing Lyme borreliosis (LB) - a multisystem disease that is often referred to as the 'great imitator' due to diversity of its clinical manifestations. Among the genospecies that commonly infect people, i.e. B. burgdorferi s.s., B. afzelii, and B. garinii, only B. burgdorferi s.s. causes LB both in the USA and in Europe, with a wide spectrum of clinical conditions ranging from minor cutaneous erythema migrans (EM) to severe arthritis or neurological manifestations. The epidemiological data from many European countries and the USA show a dramatic increase of the diagnosed cases of LB due to the development of new progressive diagnostic methods during the last decades (Hubálek, 2009). Recently, the definition of the disease has also changed. What was not considered Lyme borreliosis before might be now.

• MeSH
• Arachnid Vectors microbiology   physiology   MeSH
• Borrelia burgdorferi classification   genetics   isolation & purification   pathogenicity   MeSH
• DNA, Bacterial genetics   MeSH
• Species Specificity MeSH
• Phylogeny MeSH
• Phylogeography MeSH
• Genetic Variation MeSH
• Rodentia MeSH
• Ticks microbiology   physiology   MeSH
• Humans MeSH
• Lyme Disease * diagnosis   epidemiology   microbiology   transmission   MeSH
• Polymerase Chain Reaction MeSH
• Birds MeSH
• Bacterial Typing Techniques methods   MeSH
• Public Health MeSH
• Disease Reservoirs MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geographicals
• Asia MeSH
• Europe MeSH
• United States MeSH
• Names of Substances
• DNA, Bacterial MeSH