Despite the significant health risks associated with Dermanyssus gallinae infestations in humans, they are often overlooked. This study investigated a household case of D. gallinae infestation and explored the resulting clinical manifestations and risk of infection in family members. Microfluidic PCR was employed for high-throughput screening of pathogens in collected mites and blood samples from both chickens and family members. Morphological and molecular examinations confirmed the identity of the mites as D. gallinae sensu stricto (s.s.), with evidence indicating recent blood feeding. Results indicated that the mites exclusively harbored various pathogens, including Bartonella spp., Ehrlichia spp., Apicomplexa, and Theileria spp. Blood samples from family members and poultry tested negative for these pathogens, suggesting a potential reservoir role for D. gallinae. The study further identified haplotypes of D. gallinae, classifying them into D. gallinae s.s., cosmopolitan haplogroup A. Serological analysis revealed elevated IgE seroreactivity against mite proteins in the family member with bite lesions. Antibodies against Bartonella spp. were detected in this individual, indicating exposure to the pathogen. In summary, this study sheds light on the clinical manifestations, pathogen detection, and genetic characterization of D. gallinae infestations, underscoring the necessity of adopting comprehensive approaches to manage such infestations effectively.

• Publikační typ
• časopisecké články MeSH

• MeSH
• civilní obrana MeSH
• informační služby MeSH
• kongresy jako téma MeSH
• ochrana veřejného zdraví MeSH
• řízení rizik * MeSH
• Publikační typ
• zprávy MeSH

• MeSH
• COVID-19 prevence a kontrola   MeSH
• hasiči MeSH
• kontrola infekčních nemocí MeSH
• požáry prevence a kontrola   MeSH
• urgentní zdravotnické služby MeSH
• záchranná práce MeSH
• Geografické názvy
• Česká republika MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• management, organizace a řízení zdravotnictví
• urgentní lékařství
• pneumologie a ftizeologie
• NLK Publikační typ
• brožury

• MeSH
• bezpečnostní opatření MeSH
• informační systémy MeSH
• kongresy jako téma MeSH
• radiační ochrana MeSH

By searching nucleotide databases for the North American Lyme disease vector, Ixodes scapularis, we have complemented the previously characterized European Ixodes ricinus legumain IrAE1 with a full set of nine analogous genes (isae1-9). Six of these were PCR confirmed as genes present in all tick genomes tested. The absolute mRNA copy number examined by quantitative (q)PCR enabled expression profiling and an absolute comparison of mRNA levels for individual I. scapularis (Is)AEs in tick tissues. Four IsAEs (1, 2, 4, 9) were expressed solely in the gut and thus are proposed to be involved in host blood digestion. Expression qPCR profiling over developmental stages confirmed IsAE1, the direct analogue of previously characterized I. ricinus IrAE1, as the principle legumain transcript in partially engorged females, and demonstrated its strong regulation by on-host feeding in larvae, nymphs and females. In contrast, IsAE2 was the predominant gut legumain in unfed nymphs, unfed females and males. In-silico, IsAE1 and IsAE2 protein three-dimensional structural models displayed minimal differences in overall proenzyme structures, even in comparison with recently resolved crystal structures of mammalian prolegumain. Three functional studies were performed in I. ricinus with IsAE1/IsAE2 analogues: double IrAE1/IrAE2 RNA interference silencing, feeding of ticks on IrAE1+IrAE2 immunized hosts and in vitro membrane tick feeding on blood containing a legumain-specific inhibitor. The latter experiment led to reduced weights of fully engorged ticks and limited oviposition, and indicated the potential of legumain inhibitors for novel anti-tick interventions.

• MeSH
• arachnida jako vektory enzymologie   MeSH
• cysteinové endopeptidasy klasifikace   genetika   metabolismus   MeSH
• infestace klíšťaty prevence a kontrola   veterinární   MeSH
• izoenzymy MeSH
• klíště enzymologie   MeSH
• klonování DNA MeSH
• konformace proteinů MeSH
• králíci MeSH
• molekulární modely MeSH
• proteiny členovců klasifikace   genetika   metabolismus   MeSH
• regulace genové exprese enzymů MeSH
• rekombinantní proteiny imunologie   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• vakcíny imunologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• Červený kříž MeSH
• lidé MeSH
• urgentní zdravotnické služby * MeSH
• voda * MeSH
• záchranná práce MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH

Babesiosis is a tick-transmitted zoonosis caused by apicomplexan parasites of the genus Babesia. Treatment of this emerging malaria-related disease has relied on antimalarial drugs and antibiotics. The proteasome of Plasmodium, the causative agent of malaria, has recently been validated as a target for anti-malarial drug development and therefore, in this study, we investigated the effect of epoxyketone (carfilzomib, ONX-0914 and epoxomicin) and boronic acid (bortezomib and ixazomib) proteasome inhibitors on the growth and survival of Babesia. Testing the compounds against Babesia divergens ex vivo revealed suppressive effects on parasite growth with activity that was higher than the cytotoxic effects on a non-transformed mouse macrophage cell line. Furthermore, we showed that the most-effective compound, carfilzomib, significantly reduces parasite multiplication in a Babesia microti infected mouse model without noticeable adverse effects. In addition, treatment with carfilzomib lead to an ex vivo and in vivo decrease in proteasome activity and accumulation of polyubiquitinated proteins compared to untreated control. Overall, our results demonstrate that the Babesia proteasome is a valid target for drug development and warrants the design of potent and selective B. divergens proteasome inhibitors for the treatment of babesiosis.

• MeSH
• Babesia microti účinky léků   genetika   růst a vývoj   MeSH
• Babesia účinky léků   genetika   růst a vývoj   MeSH
• babezióza farmakoterapie   MeSH
• buněčné linie MeSH
• inhibitory proteasomu aplikace a dávkování   škodlivé účinky   farmakologie   terapeutické užití   MeSH
• kyseliny boronové farmakologie   MeSH
• lékové transportní systémy * MeSH
• makrofágy účinky léků   parazitologie   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• oligopeptidy farmakologie   MeSH
• proteasomový endopeptidasový komplex účinky léků   MeSH
• proteom účinky léků   genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• validační studie MeSH

Inhibition of aspartic cathepsin D-like peptidases (APDs) has been often discussed as an antiparasite intervention strategy. APDs have been considered as virulence factors of Trypanosoma cruzi and Leishmania spp., and have been demonstrated to have important roles in protein trafficking mechanisms of apicomplexan parasites. APDs also initiate blood digestion as components of multienzyme proteolytic complexes in malaria, platyhelminths, nematodes, and ticks. Increasing DNA and RNA sequencing data indicate that parasites express multiple APD isoenzymes of various functions that can now be specifically evaluated using new functional-genomic and biochemical tools, from which we can further assess the potential of APDs as targets for novel effective intervention strategies against parasitic diseases that still pose an alarming threat to mankind.

• MeSH
• antiparazitární látky farmakologie   terapeutické užití   MeSH
• inhibitory enzymů farmakologie   MeSH
• lékové transportní systémy * MeSH
• parazitární nemoci farmakoterapie   enzymologie   MeSH
• paraziti enzymologie   MeSH
• proteasy metabolismus   MeSH
• transport proteinů genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Limulus Clotting Factor C is a multi-domain serine protease that triggers horseshoe crab hemolymph clotting in the presence of trace amounts of bacterial lipopolysaccharides. Here we describe and functionally characterize an homologous molecule, designated as IrFC, from the hard tick Ixodes ricinus. Tick Factor C consists of an N-terminal cysteine-rich domain, four complement control protein (sushi) modules, an LCCL domain, a truncated C-lectin domain and a C-terminal trypsin-type domain. Developmental expression profiling by quantitative real-time PCR revealed that the irfc mRNA is expressed in all stages including eggs. In tissues dissected from adult I. ricinus females, the irfc mRNA is present mainly in tick hemocytes and accordingly, indirect immunofluorescence microscopy localized IrFC intracellularly, in tick hemocytes. Irfc mRNA levels were markedly increased upon injection of sterile saline, or different microbes, demonstrating that the irfc gene transcription occurs in response to injury. This indicates a possible role of IrFC in hemolymph clotting and/or wound healing, although these defense mechanisms have not been yet definitely demonstrated in ticks. RNAi silencing of irfc expression resulted in a significant reduction in phagocytic activity of tick hemocytes against the Gram-negative bacteria Chryseobacterium indologenes and Escherichia coli, but not against the yeast, Candida albicans. This result suggests that IrFC plays a role in the tick primordial complement system and as such possibly mediates transmission of tick-borne pathogens.

• MeSH
• Borrelia imunologie   MeSH
• Candida albicans imunologie   MeSH
• Escherichia coli imunologie   MeSH
• exprese genu MeSH
• fagocytóza MeSH
• klíště enzymologie   genetika   imunologie   mikrobiologie   MeSH
• komplement fyziologie   MeSH
• messenger RNA biosyntéza   genetika   MeSH
• Micrococcus luteus imunologie   MeSH
• molekulární sekvence - údaje MeSH
• prekurzory enzymů biosyntéza   genetika   MeSH
• přirozená imunita MeSH
• proteiny členovců biosyntéza   genetika   MeSH
• serinové endopeptidasy biosyntéza   genetika   MeSH
• upregulace imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH