Project description:Transcriptional profiling of NHDF Cells comparing control untreated fibroblasts with fibroblasts coincubated with three different species of the Borrelia burgdorferi sensu lato group.
Project description:The similarity of Lyme borreliosis to other diseases and the complex pathogenesis cause diagnostic and therapeutic difficulties. Changes at the cellular and molecular level after Borrelia sp. infection remain still poorly understood. Therefore, the present study focused on the gene expression in human dermal fibroblasts in differentiation of infection with Borrelia garinii, Borrelia afzelii and Borrelia burgdorferi sensu stricto spirochetes. For microarray analysis 10 samples were used: 3 control samples - K, 2 samples of NHDF cells infected with Borrelia garinii - G, 2 samples of NHDF cells infected with Borrelia afzelii - A and 3 samples of NHDF cells infected with Borrelia burgdorferi sensu stricto - SS.
Project description:The Lyme disease spirochete Borrelia burgdorferi drives a range of acute and chronic maladies in humans and other incidental hosts infected with the pathogen. However, the primary vertebrate reservoir, Peromyscus leucopus appears spared from any symptomology following infection. This has led to a common hypothesis that P. leucopus and B. burgdorferi exist symbiotically: P. leucopus restrain their immune response against the microbe and enable the enzootic cycle while B. burgdorferi avoids causing damage to the host. While aspects of this hypothesis have been tested, the exact interactions that occur between P. leucopus and B. burgdorferi during infection remain largely unknown. Here we utilized an inbred colony of P. leucopus in order to compare B. burgdorferi (B31) fitness in these rodents to the traditional B. burgdorferi murine models—C57BL/6J and C3H/HeN Mus musculus, which develop signs of inflammation akin to human disease. We find that in contrast to our expectations, B. burgdorferi were able to reach much higher burdens in M. musculus, and that the overall kinetics of infection differed between the two rodent species. Surprisingly, we also found that P. leucopus remained infectious to larval Ixodes scapularis for a far shorter period than either M. musculus strain. In line with these observations, we found that P. leucopus does launch a modest but sustained inflammatory response against B. burgdorferi in the skin, which we hypothesize leads to reduced bacterial viability and infectivity in these hosts. These observations provide new insight into the nature of reservoir species and the B. burgdorferi enzootic cycle.
Project description:Lyme disease is a result from an infection by the spirochete Borrelia burgdorferi, and is the leading vector-borne disease in North America. Due to the genomic and proteomic variability of different B. burgdorferi isolates, the study and further comparison of their proteome is key to understand the biology and infectivity of these spirochetes. Mass spectrometry-based proteomics was used to assemble peptide datasets of laboratory isolates B31, MM1, B31-ML23, and the infective isolates B31-5A4, B31-A3, and 297, as well as other public datasets, and is publicly available as the Borrelia PeptideAtlas (http://www.peptideatlas.org/builds/borrelia/). These datasets include information on total proteome, secretome, and membrane proteome of the B. burgdorferi.
Project description:The similarity of Lyme borreliosis to other diseases and the complex pathogenesis cause diagnostic and therapeutic difficulties. Changes at the cellular and molecular level after Borrelia sp. infection remain still poorly understood. Therefore, the present study focused on the gene expression in human dermal fibroblasts in differentiation of infection with Borrelia garinii, Borrelia afzelii and Borrelia burgdorferi sensu stricto spirochetes.
Project description:Lyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agent Borrelia burgdorferi. Immunodiagnostic assays for canine antibodies to B. burgdorferi are usually based on whole-cell preparations as substrate and, consequently, interpretation of results is confounded by antibody cross-reactivity between borrelial antigens and those of other bacterial species. To more broadly characterize the antibody responses to B. burgdorferi infection and to assess the diversity in those responses between individual dogs, we examined sera from 32 adult, colony-bred beagle dogs that were experimentally infected with B. burgdorferi through tick bites and compared those on a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encoded B. burgdorferi proteins, including 24 of the serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural reservoir rodents. These included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals here demonstrated diversity in antibody responses by measures of antibody levels and specificities for conserved proteins, like DbpB, and polymorphic ones, like OspC.
Project description:Lyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agent Borrelia burgdorferi. Immunodiagnostic assays for canine antibodies to B. burgdorferi are usually based on whole-cell preparations as substrate and, consequently, interpretation of results is confounded by antibody cross-reactivity between borrelial antigens and those of other bacterial species. To more broadly characterize the antibody responses to B. burgdorferi infection and to assess the diversity in those responses between individual dogs, we examined sera from 32 adult, colony-bred beagle dogs that were experimentally infected with B. burgdorferi through tick bites and compared those on a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encoded B. burgdorferi proteins, including 24 of the serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural reservoir rodents. These included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals here demonstrated diversity in antibody responses by measures of antibody levels and specificities for conserved proteins, like DbpB, and polymorphic ones, like OspC.