The genetic diversity of Borrelia afzelii is not maintained by the diversity of the rodent hosts.

Small mammals are essential in the enzootic cycle of many tick-borne pathogens (TBP). To understand their contribution to the genetic diversity of Borrelia afzelii, the most prevalent TBP in questing Ixodes ricinus, we compared the genetic variants of B. afzelii at three distinct genetic loci. We chose two plasmid loci, dbpA and ospC, and a chromosomal one, IGS

Ixodes ricinus ticks are reservoir hosts for Rickettsia helvetica and potentially carry flea-borne Rickettsia species

Rickettsia specie

Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus

Human islet amyloid polypeptide (hIAPP), a pancreatic islet protein of 37 amino acids, is the main component of islet amyloid, seen at autopsy in patients with type 2 diabetes mellitus (DM2). To investigate the roles of hIAPP and islet amyloid in DM2, we generated transgenic mice expressing hIAPP in their islet beta cells. In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process

Absence of zoonotic Bartonella species in questing ticks: First detection of Bartonella clarridgeiae and Rickettsia felis in cat fleas in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Awareness for flea- and tick-borne infections has grown in recent years and the range of microorganisms associated with these ectoparasites is rising. <it>Bartonella henselae</it>, the causative agent of Cat Scratch Disease, and other <it>Bartonella </it>species have been reported in fleas and ticks. The role of <it>Ixodes ricinus </it>ticks in the natural cycle of <it>Bartonella </it>spp. and the transmission of these bacteria to humans is unclear. <it>Rickettsia </it>spp. have also been reported from as well ticks as also from fleas. However, to date no flea-borne <it>Rickettsia </it>spp. were reported from the Netherlands. Here, the presence of <it>Bartonellaceae </it>and <it>Rickettsiae </it>in ectoparasites was investigated using molecular detection and identification on part of the gltA- and 16S rRNA-genes.</p> <p>Results</p> <p>The zoonotic <it>Bartonella clarridgeiae </it>and <it>Rickettsia felis </it>were detected for the first time in Dutch cat fleas. <it>B. henselae </it>was found in cat fleas and <it>B. schoenbuchensis </it>in ticks and keds feeding on deer. Two <it>Bartonella </it>species, previously identified in rodents, were found in wild mice and their fleas. However, none of these microorganisms were found in 1719 questing <it>Ixodes ricinus </it>ticks. Notably, the gltA gene amplified from DNA lysates of approximately 10% of the questing nymph and adult ticks was similar to that of an uncultured <it>Bartonella-</it>related species found in other hard tick species. The gltA gene of this <it>Bartonella-</it>related species was also detected in questing larvae for which a 16S rRNA gene PCR also tested positive for "<it>Candidatus </it>Midichloria mitochondrii"<it/>. The gltA-gene of the <it>Bartonella-</it>related species found in <it>I. ricinus </it>may therefore be from this endosymbiont.</p> <p>Conclusions</p> <p>We conclude that the risk of acquiring Cat Scratch Disease or a related bartonellosis from questing ticks in the Netherlands is negligible. On the other hand fleas and deer keds are probable vectors for associated <it>Bartonella </it>species between animals and might also transmit <it>Bartonella </it>spp. to humans.</p

The circulation of Anaplasma phagocytophilum ecotypes is associated with community composition of vertebrate hosts

Anaplasma phagocytophilum is a tick-borne pathogen that has been detected in many tick and vertebrate species. It is among the most widespread tick-borne pathogens in animals in Europe. The bacterium can be genetically divided into four ecotypes, which are linked to distinct but overlapping host species. However, knowledge about the transmission dynamics of the enzootic cycles of the different ecotypes is limited. Here, we quantified the link between the ecotypes of A. phagocytophilum, the different life stages of the tick Ixodes ricinus, and vertebrate host groups through a meta-analysis. We extracted data on the mean I. ricinus burden and the A. phagocytophilum infection prevalence in both hosts and feeding I. ricinus from 197 papers on 77 wildlife species. With this information, we modeled the relative importance of different host taxonomic groups for the circulation of the different ecotypes of A. phagocytophilum in a theoretical assemblage of hosts with varying presence of red deer (Cervus elaphus) and densities of small mammals. We showed that the composition of the vertebrate community affects the relative abundance of different ecotypes of A. phagocytophilum in the different life stages of I. ricinus. The presence of red deer is likely to increase the infection prevalence of Ecotype 1 in ticks, while small mammal densities drive the prevalence in ticks of mainly Ecotype 3, and to a lesser extent Ecotype 1. In Europe, vertebrate communities are changing, with an increase in red deer abundance and changes in the population dynamics of small mammals. Our results suggest that these changes could imply an increase in the circulation of A. phagocytophilum and thus an increase in the risk for public and veterinary health

High-throughput screening of tick-borne pathogens in Europe

Due to increased travel, climatic, and environmental changes, the incidence of tick-borne disease in both humans and animals is increasing throughout Europe. Therefore, extended surveillance tools are desirable. To accurately screen tick-borne pathogens (TBPs), a large scale epidemiological study was conducted on 7050 Ixodes ricinus nymphs collected from France, Denmark, and the Netherlands using a powerful new high-throughput approach. This advanced methodology permitted the simultaneous detection of 25 bacterial, and 12 parasitic species (including; Borrelia, Anaplasma, Ehrlichia, Rickettsia, Bartonella, Candidatus Neoehrlichia, Coxiella, Francisella, Babesia, and Theileria genus) across 94 samples. We successfully determined the prevalence of expected (Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Rickettsia helvetica, Candidatus Neoehrlichia mikurensis, Babesia divergens, Babesia venatorum), unexpected (Borrelia miyamotoi), and rare (Bartonella henselae) pathogens in the three European countries. Moreover we detected Borrelia spielmanii, Borrelia miyamotoi, Babesia divergens, and Babesia venatorum for the first time in Danish ticks. This surveillance method represents a major improvement in epidemiological studies, able to facilitate comprehensive testing of TBPs, and which can also be customized to monitor emerging diseases

Diverse tick-borne microorganisms identified in free-living ungulates in Slovakia

Background: Free-living ungulates are hosts of ixodid ticks and reservoirs of tick-borne microorganisms in central Europe and many regions around the world. Tissue samples and engorged ticks were obtained from roe deer, red deer, fallow deer, mouflon, and wild boar hunted in deciduous forests of south-western Slovakia. DNA isolated from these samples was screened for the presence of tick-borne microorganisms by PCR-based methods. Results: Ticks were found to infest all examined ungulate species. The principal infesting tick was Ixodes ricinus, identified on 90.4% of wildlife, and included all developmental stages. Larvae and nymphs of Haemaphysalis concinna were feeding on 9.6% of wildlife. Two specimens of Dermacentor reticulatus were also identified. Ungulates were positive for A. phagocytophilum and Theileria spp. Anaplasma phagocytophilum was found to infect 96.1% of cervids, 88.9% of mouflon, and 28.2% of wild boar, whereas Theileria spp. was detected only in cervids (94.6%). Importantly, a high rate of cervids (89%) showed mixed infections with both these microorganisms. In addition to A. phagocytophilum and Theileria spp., Rickettsia helvetica, R. monacensis, unidentified Rickettsia sp., Coxiella burnetii, "Candidatus Neoehrlichia mikurensis", Borrelia burgdorferi (s.l.) and Babesia venatorum were identified in engorged I. ricinus. Furthermore, A. phagocytophilum, Babesia spp. and Theileria spp. were detected in engorged H. concinna. Analysis of 16S rRNA and groEL gene sequences revealed the presence of five and two A. phagocytophilum variants, respectively, among which sequences identified in wild boar showed identity to the sequence of the causative agent of human granulocytic anaplasmosis (HGA). Phylogenetic analysis of Theileria 18S rRNA gene sequences amplified from cervids and engorged I. ricinus ticks segregated jointly with sequences of T. capreoli isolates into a moderately supported monophyletic clade. Conclusions: The findings indicate that free-living ungulates are reservoirs for A. phagocytophilum and Theileria spp. and engorged ixodid ticks attached to ungulates are good sentinels for the presence of agents of public and veterinary concern. Further analyses of the A. phagocytophilum genetic variants and Theileria species and their associations with vector ticks and free-living ungulates are required.Fil: Kazimírová, Mária. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Hamšíková, Zuzana. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Spitalská, Eva. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; EslovaquiaFil: Minichová, Lenka. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; EslovaquiaFil: Mahríková, Lenka. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Caban, Radoslav. Široká ; EslovaquiaFil: Sprong, Hein. National Institute for Public Health and Environment.Laboratory for Zoonoses and Environmental Microbiology; Países BajosFil: Fonville, Manoj. National Institute for Public Health and Environment.Laboratory for Zoonoses and Environmental Microbiology; Países BajosFil: Schnittger, Leonhard. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kocianová, Elena. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; Eslovaqui

A type III complement factor D deficiency: Structural insights for inhibition of the alternative pathway.

Abstract Background: Complement factor D (FD) is the rate-limiting enzyme of the alternative complement pathway. Previous reports of FD deficiency featured absent plasma FD (type I deficiency) and susceptibility to meningococcal infection. A new FD mutant, which is non-functional but fully expressed, was identified in a patient with invasive meningococcal disease. Objectives: We sought to investigate the molecular features of this novel FD mutant. Methods: We performed complement haemolytic assays, western blot analysis of serum FD and Sanger sequencing of the CFD gene. Recombinant mutant FD was assessed by in vitro catalytic assays, circular dichroism, thermal shift assays, esterolytic assays and surface plasmon resonance. Molecular dynamics simulation was used to visualise the structural changes in mutant FD. Results: A homozygous single-nucleotide variation of the CFD gene in the patient and their sibling resulted in an arginine to proline (R176P) substitution in FD. While R176P FD was stable and fully expressed in blood, it had minimal catalytic activity. Mutation R176P caused key FD-C3bB binding exosite loop 156-162 to lose its binding-competent conformation and stabilised the inactive conformation of FD. Consequently, R176P FD was unable to bind its natural substrate, C3bB. Neither patient nor sibling demonstrated the glucose homeostasis impairment that occurs in FD-null mice. Conclusions: Here, we report the first genetically confirmed functional, or type III, deficiency of an activating complement serine protease. This novel mechanism of FD inhibition can inform further development of alternative pathway inhibitors to treat common inflammatory diseases such as age-related macular degeneration

Temperament and character in men with autism spectrum disorder: A reanalysis of scores on the Temperament and Character Inventory by individual case matching

Background: Interest in autism spectrum disorders (ASD) in adulthood is increasing. Although a person may be diagnosed with ASD, the diagnosis reveals little about the individual's temperament, character, and personality. Also, relatively little is known about the personality of adults with ASD. Method: A reanalysis of scores on the Temperament and Character Inventory (TCI) administered to a group of 66 normally intelligent men aged 18–63 years, diagnosed with ASD, by individual case matching to a comparison group of 66 men from the general population drawn from the TCI manual. Results: Compared to the comparison group, men with ASD scored significantly higher on the scale for Harm Avoidance, and lower on Novelty Seeking, Reward Dependence, Self-Directedness, and Cooperativeness. Conclusions: In this study the score pattern for temperament and character found in men with ASD by individual case matching confirms and strengthens earlier general group matching findings emerging from our 2012 study and from studies from Sweden and the Netherlands