DipA, a pore-forming protein in the outer membrane of lyme disease spirochetes exhibits specificity for the permeation of dicarboxylate

Lyme disease Borreliae are highly dependent on the uptake of nutrients provided by their hosts. Our study describes the identification of a 36 kDa protein that functions as putative dicarboxylate-specific porin in the outer membrane of Lyme disease Borrelia. The protein was purified by hydroxyapatite chromatography from Borrelia burgdorferi B31 and designated as DipA, for dicarboxylate-specific porin A. DipA was partially sequenced, and corresponding genes were identified in the genomes of B. burgdorferi B31, Borrelia garinii PBi and Borrelia afzelii PKo. DipA exhibits high homology to the Oms38 porins of relapsing fever Borreliae. B. burgdorferi DipA was characterized using the black lipid bilayer assay. The protein has a singlechannel conductance of 50 pS in 1 M KCl, is slightly selective for anions with a permeability ratio for cations over anions of 0.57 in KCl and is not voltage-dependent. The channel could be partly blocked by different di- and tricarboxylic anions. Particular high stability constants up to about 28,000 l/mol (in 0.1 M KCl) were obtained among the 11 tested anions for oxaloacetate, 2-oxoglutarate and citrate. The results imply that DipA forms a porin specific for dicarboxylates which may play an important role for the uptake of specific nutrients in different Borrelia species

Borrelia burgdorferi infection in a natural population of Peromyscus leucopus mice: A longitudinal study in an area where lyme borreliosis is highly endemic

Blood samples from Peromyscus leucopus mice captured at an enzootic site in Connecticut were examined for antibodies to and DNA of Borrelia burgdorferi, to characterize the dynamics of infection in this reservoir population. From trappings conducted over the course of 2 transmission seasons, 598 (75%) of 801 serum samples from 514 mice were found to be positive by enzyme immunoassay. Seropositivity correlated with date of capture and mouse age, was similar among locations within the site, increased from 57% to 93% over the course of the transmission season, and was associated with antibodies to outer surface protein (Osp) C, but not to OspA. Longitudinal samples from 184 mice revealed an incidence of 0.2 cases/mouse/week. Nineteen (10%) of 187 samples were found by polymerase chain reaction to be positive for B. burgdorferi, and, of those, 14 (74%) were found to be seropositive. Nearly the entire population of P. leucopus mice became infected with B. burgdorferi by late August, coinciding with the peak activity period of host-seeking larvae uninfected with the spirochete Ixodes scapularis, thereby perpetuating the agent through succeeding generations of ticks.Centro de Estudios Parasitológicos y de VectoresFacultad de Ciencias Naturales y Muse

Migratory Passerine Birds as Reservoirs of Lyme Borreliosis in Europe

Birds host vector ticks and Borrelia species and vary in effectiveness as reservoirs

Typing of Borrelia Relapsing Fever Group Strains

Partial sequencing of the 16S-23S rDNA intergenic spacer showed two to four genotypes each for Borrelia hermsii and B. turicatae, both relapsing fever agents transmitted by argasid ticks, and for B. miyamotoi and B. lonestari, transmitted by ixodid ticks. Field surveys of Ixodes ticks in Connecticut and Sweden showed limited local diversity for B. miyamotoi

Borrelia burgdorferi infection in a natural population of Peromyscus leucopus mice: A longitudinal study in an area where lyme borreliosis is highly endemic

Blood samples from Peromyscus leucopus mice captured at an enzootic site in Connecticut were examined for antibodies to and DNA of Borrelia burgdorferi, to characterize the dynamics of infection in this reservoir population. From trappings conducted over the course of 2 transmission seasons, 598 (75%) of 801 serum samples from 514 mice were found to be positive by enzyme immunoassay. Seropositivity correlated with date of capture and mouse age, was similar among locations within the site, increased from 57% to 93% over the course of the transmission season, and was associated with antibodies to outer surface protein (Osp) C, but not to OspA. Longitudinal samples from 184 mice revealed an incidence of 0.2 cases/mouse/week. Nineteen (10%) of 187 samples were found by polymerase chain reaction to be positive for B. burgdorferi, and, of those, 14 (74%) were found to be seropositive. Nearly the entire population of P. leucopus mice became infected with B. burgdorferi by late August, coinciding with the peak activity period of host-seeking larvae uninfected with the spirochete Ixodes scapularis, thereby perpetuating the agent through succeeding generations of ticks.Centro de Estudios Parasitológicos y de VectoresFacultad de Ciencias Naturales y Muse

An ecological approach to preventing human infection: Vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle

Many pathogens, such as the agents of West Nile encephalitis and plague, are maintained in nature by animal reservoirs and transmitted to humans by arthropod vectors. Efforts to reduce disease incidence usually rely on vector control or immunization of humans. Lyme disease, for which no human vaccine is currently available, is a commonly reported vector-borne disease in North America and Europe. In a recently developed, ecological approach to disease prevention, we intervened in the natural cycle of the Lyme disease agent (Borrelia burgdorferi) by immunizing wild white-footed mice (Peromyscus leucopus), a reservoir host species, with either a recombinant antigen of the pathogen, outer surface protein A, or a negative control antigen in a repeated field experiment with paired experimental and control grids stratified by site. Outer surface protein A vaccination significantly reduced the prevalence of B. burgdorferi in nymphal blacklegged ticks (Ixodes scapularis) collected at the sites the following year in both experiments. The magnitude of the vaccine's effect at a given site correlated with the tick infection prevalence found on the control grid, which in turn correlated with mouse density. These data, as well as differences in the population structures of B. burgdorferi in sympatric ticks and mice, indicated that nonmouse hosts contributed more to infecting ticks than previously expected. Thus, where nonmouse hosts play a large role in infection dynamics, vaccination should be directed at additional species.Facultad de Ciencias Naturales y MuseoCentro de Estudios Parasitológicos y de Vectore

Complex Population Structure of Lyme Borreliosis Group Spirochete Borrelia garinii in Subarctic Eurasia

Borrelia garinii, a causative agent of Lyme borreliosis in Europe and Asia, is naturally maintained in marine and terrestrial enzootic cycles, which primarily involve birds, including seabirds and migratory passerines. These bird groups associate with, correspondingly, Ixodes uriae and Ixodes ricinus ticks, of which the latter species may bite and transmit the infection to humans. Studies of the overlap between these two natural cycles of B. garinii have been limited, in part due to the absence of representative collections of this spirochete's samples, as well as of the lack of reliable measure of the genetic heterogeneity of its strains. As a prerequisite for understanding the epidemiological correlates of the complex maintenance of B. garinii, the present study sought to assess the diversity and phylogenetic relationships of this species' strains from its natural hosts and patients with Lyme borreliosis from subarctic Eurasia. We used sequence typing of the partial rrs-rrl intergenic spacer (IGS) of archived and prospective samples of B. garinii from I. uriae ticks collected predominantly on Commander Islands in North Pacific, as well as on the islands in northern Sweden and arctic Norway. We also typed B. garinii samples from patients with Lyme borreliosis and I. ricinus ticks infesting migratory birds in southern Sweden, or found questing in selected sites on the islands in the Baltic Sea and Lithuania. Fifty-two (68%) of 77 B. garinii samples representing wide geographical range and associated with I. ricinus and infection of humans contributed 12 (60%) of total 20 identified IGS variants. In contrast, the remaining 25 (32%) samples recovered from I. uriae ticks from a few islands accounted for as many as 10 (50%) IGS types, suggesting greater local diversity of B. garinii maintained by seabirds and their ticks. Two IGS variants of the spirochete in common for both tick species were found in I. ricinus larvae from migratory birds, an indication that B. garinii strains are exchanged between different ecological niches. Notably, B. garinii variants associated with I. uriae ticks were found in each of the six clusters, representing two phylogenetic lineages of this species identified among the studied samples. Our findings suggest that B. garinii in subarctic Eurasia comprises two partially overlapping populations with different levels of genetic heterogeneity, presumably, due to distinctive selective pressures on the spirochete in its marine and terrestrial enzootic cycles

Ведение беременных с преэклампсией в женской консультации

ЖЕНЩИНЫ БЕРЕМЕННЫЕБЕРЕМЕННОСТЬБЕРЕМЕННОСТИ ОСЛОЖНЕНИЯГИПЕРТЕНЗИЯ, ВЫЗВАННАЯ БЕРЕМЕННОСТЬЮ /ПРОФПРЕЭКЛАМПСИЯГЕСТОЗЖЕНСКИЕ КОНСУЛЬТАЦИ

Combination of short-read, long-read, and optical mapping assemblies reveals large-scale tandem repeat arrays with population genetic implications

Accurate and contiguous genome assembly is key to a comprehensive understanding of the processes shaping genomic diversity and evolution. Yet, it is frequently constrained by constitutive heterochromatin, usually characterized by highly repetitive DNA. As a key feature of genome architecture associated with centromeric and subtelomeric regions, it locally influences meiotic recombination. In this study, we assess the impact of large tandem repeat arrays on the recombination rate landscape in an avian speciation model, the Eurasian crow. We assembled two high-quality genome references using single-molecule real-time sequencing (long-read assembly [LR]) and single-molecule optical maps (optical map assembly [OM]). A three-way comparison including the published short-read assembly (SR) constructed for the same individual allowed assessing assembly properties and pinpointing misassemblies. By combining information from all three assemblies, we characterized 36 previously unidentified large repetitive regions in the proximity of sequence assembly breakpoints, the majority of which contained complex arrays of a 14-kb satellite repeat or its 1.2-kb subunit. Using whole-genome population resequencing data, we estimated the population-scaled recombination rate (ρ) and found it to be significantly reduced in these regions. These findings are consistent with an effect of low recombination in regions adjacent to centromeric or subtelomeric heterochromatin and add to our understanding of the processes generating widespread heterogeneity in genetic diversity and differentiation along the genome. By combining three different technologies, our results highlight the importance of adding a layer of information on genome structure that is inaccessible to each approach independently

Geographic Differences in Genetic Locus Linkages for Borrelia burgdorferi

Borrelia burdorferi genotype in the northeastern United States is associated with Lyme borreliosis severity. Analysis of DNA sequences of the outer surface protein C gene and rrs-rrlA intergenic spacer from extracts of Ixodes spp. ticks in 3 US regions showed linkage disequilibrium between the 2 loci within a region but not consistently between regions