230 research outputs found
Human Antibody Responses to VlsE Antigenic Variation Protein of Borrelia burgdorferi
VlsE is a 35-kDa surface-exposed lipoprotein of Borrelia burgdorferi that was shown previously to undergo antigenic variation through segmental recombination of silent vls cassettes with vlsE during experimental mouse infections. Previous data had indicated that sera from North American Lyme disease patients and experimentally infected animals contained antibodies reactive with VlsE. In this study, sera from patients with Lyme disease, syphilis, and autoimmune conditions as well as from healthy controls were examined for reactivity with VlsE by Western blotting and enzyme-linked immunosorbent assay (ELISA). Strong Western blot reactivity to a recombinant VlsE cassette region protein was obtained consistently with Lyme disease sera. Although sera from Lyme disease patients also reacted with a band corresponding to VlsE in B. burgdorferi B31-5A3, interpretation was complicated by low levels of VlsE expression in in vitro-cultured B. burgdorferi and by the presence of comigrating bands. An ELISA using recombinant VlsE was compared with an ELISA using sonically disrupted B. burgdorferi as the antigen. For a total of 93 Lyme disease patient sera examined, the VlsE ELISA yielded sensitivities of 63% for culture-confirmed erythema migrans cases and 92% for later stages, as compared to 61 and 98%, respectively, for the “whole-cell” ELISA. The specificities of the two assays with healthy blood donor sera were comparable, but the VlsE ELISA was 90% specific with sera from syphilis patients, compared to 20% specificity for the whole-cell ELISA with this group. Neither assay showed reactivity with a panel of sera from 20 non-Lyme disease arthritis patients or 20 systemic lupus erythematosus patients. Our results indicate that VlsE may be useful in the immunodiagnosis of Lyme disease and may offer greater specificity than ELISAs using whole B. burgdorferi as the antigen
A hierarchical network approach for modeling Rift Valley fever epidemics with applications in North America
Rift Valley fever is a vector-borne zoonotic disease which causes high
morbidity and mortality in livestock. In the event Rift Valley fever virus is
introduced to the United States or other non-endemic areas, understanding the
potential patterns of spread and the areas at risk based on disease vectors and
hosts will be vital for developing mitigation strategies. Presented here is a
general network-based mathematical model of Rift Valley fever. Given a lack of
empirical data on disease vector species and their vector competence, this
discrete time epidemic model uses stochastic parameters following several PERT
distributions to model the dynamic interactions between hosts and likely North
American mosquito vectors in dispersed geographic areas. Spatial effects and
climate factors are also addressed in the model. The model is applied to a
large directed asymmetric network of 3,621 nodes based on actual farms to
examine a hypothetical introduction to some counties of Texas, an important
ranching area in the United States of America (U.S.A.). The nodes of the
networks represent livestock farms, livestock markets, and feedlots, and the
links represent cattle movements and mosquito diffusion between different
nodes. Cattle and mosquito (Aedes and Culex) populations are treated with
different contact networks to assess virus propagation. Rift Valley fever virus
spread is assessed under various initial infection conditions (infected
mosquito eggs, adults or cattle). A surprising trend is fewer initial
infectious organisms result in a longer delay before a larger and more
prolonged outbreak. The delay is likely caused by a lack of herd immunity while
the infections expands geographically before becoming an epidemic involving
many dispersed farms and animals almost simultaneously
An RND-Type Efflux System in Borrelia burgdorferi Is Involved in Virulence and Resistance to Antimicrobial Compounds
Borrelia burgdorferi is remarkable for its ability to thrive in widely different environments due to its ability to infect various organisms. In comparison to enteric Gram-negative bacteria, these spirochetes have only a few transmembrane proteins some of which are thought to play a role in solute and nutrient uptake and excretion of toxic substances. Here, we have identified an outer membrane protein, BesC, which is part of a putative export system comprising the components BesA, BesB and BesC. We show that BesC, a TolC homolog, forms channels in planar lipid bilayers and is involved in antibiotic resistance. A besC knockout was unable to establish infection in mice, signifying the importance of this outer membrane channel in the mammalian host. The biophysical properties of BesC could be explained by a model based on the channel-tunnel structure. We have also generated a structural model of the efflux apparatus showing the putative spatial orientation of BesC with respect to the AcrAB homologs BesAB. We believe that our findings will be helpful in unraveling the pathogenic mechanisms of borreliae as well as in developing novel therapeutic agents aiming to block the function of this secretion apparatus
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