Host Specificity
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The honeybee (Apis mellifera) is a key pollinator critical to global agriculture, facing threats from various stressors, including the ectoparasitic Varroa mite (Varroa destructor). Previous studies have identified shared bacteria between Varroa mites and honeybees, yet it remains unclear if these bacteria assemble similarly in both species. This study builds on existing knowledge by investigating co-occurrence patterns in the microbiomes of both Varroa mites and honeybees, shedding light on potential interactions. Leveraging 16S rRNA datasets, we conducted co-occurrence network analyses, explored Core Association Networks (CAN) and assess network robustness. Comparative network analyses revealed structural differences between honeybee and mite microbiomes, along with shared core features and microbial motifs. The mite network exhibited lower robustness, suggesting less resistance to taxa extension compared to honeybees. Furthermore, analyses of predicted functional profiling and taxa contribution revealed that common central pathways in the metabolic networks have different taxa contributing to Varroa mites and honeybee microbiomes. The results show that while both microbial systems exhibit functional redundancy, in which different taxa contribute to the functional stability and resilience of the ecosystem, there is evidence for niche specialization resulting in unique contributions to specific pathways in each part of this host-parasite system. The specificity of taxa contribution to key pathways offers targeted approaches to Varroa microbiome management and preserving honeybee microbiome. Our findings provide valuable insights into microbial interactions, aiding farmers and beekeepers in maintaining healthy and resilient bee colonies amid increasing Varroa mite infestations.
- MeSH
- Bacteria * klasifikace genetika izolace a purifikace MeSH
- mikrobiota * MeSH
- RNA ribozomální 16S genetika MeSH
- Varroidae * mikrobiologie MeSH
- včely mikrobiologie parazitologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Tick-borne encephalitis virus (TBEV) is a significant threat to human health. The virus causes potentially fatal disease of the central nervous system (CNS), for which no treatments are available. TBEV infected individuals display a wide spectrum of neuronal disease, the determinants of which are undefined. Changes to host metabolism and virus-induced immunity have been postulated to contribute to the neuronal damage observed in infected individuals. In this study, we evaluated the cytokine, chemokine, and metabolic alterations in the cerebrospinal fluid (CSF) of symptomatic patients infected with TBEV presenting with meningitis or encephalitis. Our aim was to investigate the host immune and metabolic responses associated with specific TBEV infectious outcomes. METHODS: CSF samples of patients with meningitis (n = 27) or encephalitis (n = 25) were obtained upon consent from individuals hospitalised with confirmed TBEV infection in Brno. CSF from uninfected control patients was also collected for comparison (n = 12). A multiplex bead-based system was used to measure the levels of pro-inflammatory cytokines and chemokines. Untargeted metabolomics followed by bioinformatics and integrative omics were used to profile the levels of metabolites in the CSF. Human motor neurons (hMNs) were differentiated from induced pluripotent stem cells (iPSCs) and infected with the highly pathogenic TBEV-Hypr strain to profile the role(s) of identified metabolites during the virus lifecycle. Virus infection was quantified via plaque assay. RESULTS: Significant differences in proinflammatory cytokines (IFN-α2, TSLP, IL-1α, IL-1β, GM-CSF, IL-12p40, IL-15, and IL-18) and chemokines (IL-8, CCL20, and CXCL11) were detected between neurological-TBEV and control patients. A total of 32 CSF metabolites differed in TBE patients with meningitis and encephalitis. CSF S-Adenosylmethionine (SAM), Fructose 1,6-bisphosphate (FBP1) and Phosphoenolpyruvic acid (PEP) levels were 2.4-fold (range ≥ 2.3-≥3.2) higher in encephalitis patients compared to the meningitis group. CSF urocanic acid levels were significantly lower in patients with encephalitis compared to those with meningitis (p = 0.012209). Follow-up analyses showed fluctuations in the levels of O-phosphoethanolamine, succinic acid, and L-proline in the encephalitis group, and pyruvic acid in the meningitis group. TBEV-infection of hMNs increased the production of SAM, FBP1 and PEP in a time-dependent manner. Depletion of the metabolites with characterised pharmacological inhibitors led to a concentration-dependent attenuation of virus growth, validating the identified changes as key mediators of TBEV infection. CONCLUSIONS: Our findings reveal that the neurological disease outcome of TBEV infection is associated with specific and dynamic metabolic signatures in the cerebrospinal fluid. We describe a new in vitro model for in-depth studies of TBEV-induced neuropathogenesis, in which the depletion of identified metabolites limits virus infection. Collectively, this reveals new biomarkers that can differentiate and predict TBEV-associated neurological disease. Additionally, we have identified novel therapeutic targets with the potential to significantly improve patient outcomes and deepen our understanding of TBEV pathogenesis.
- MeSH
- cytokiny mozkomíšní mok MeSH
- dospělí MeSH
- klíšťová encefalitida * mozkomíšní mok metabolismus MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolom * fyziologie MeSH
- metabolomika MeSH
- mladý dospělý MeSH
- neurony * metabolismus virologie MeSH
- senioři MeSH
- viry klíšťové encefalitidy * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Bats are the natural reservoirs for a variety of emerging and re-emerging viruses. Among them, rabies virus (genus Lyssavirus, family Rhabdoviridae) is one of the first and most emblematic described in these animals. Since its first description, several new bat lyssaviruses have been regularly identified. In addition to lyssaviruses, other bat rhabdoviruses have also been discovered, including members of the genera Vesiculovirus, Ledantevirus and, more recently, Alphanemrhavirus and Tupavirus. However, the family Rhabdoviridae is one of the most abundant and diverse viral families, with 434 officially recognized species, divided into 5 subfamilies and 56 different genera. The number of rhabdoviruses associated with bats is therefore probably higher than that currently available. In this study, we first developed and validated a combined nested RT-qPCR technique (pan-rhabdo RT-nqPCR) dedicated to the broad detection of animal rhabdoviruses. After validation, this technique was used for a large retrospective screening of archival bat samples (n = 1962), including blood (n = 816), brain (n = 723) and oral swab (n = 423). These samples were collected from various bat species over a 12-year period (2007-2019) in 9 different countries in Europe and Africa. A total of 23 samples (1.2%) from bat species Miniopterus schreibersii, Rhinolophus euryale and Rhinolophus ferrumequinum tested positive for rhabdovirus infection, including 17 (2.1%) blood and 6 (1.4%) oral swab samples, all collected from bats originating from the Mediterranean region. Complete virus genome sequences were obtained by next-generation sequencing for most of the positive samples. Molecular and phylogenetic analysis of these sequences demonstrated that the virus isolates, named Mediterranean bat virus (MBV), were closely related and represented a new species, Mediterranean vesiculovirus, within the genus Vesiculovirus. MBV was more specifically related to other bat vesiculoviruses previously described from China and North America, together clustering into a distinct group of bat viruses within this genus. Interestingly, our results suggest that MBV is widespread, at least in the western part of the Mediterranean region, where it circulates in the blood of several bat species. These results expand the host range and viral diversity of bat vesiculoviruses, and pave the way for further studies to determine the transmission route and dissemination dynamics of these viruses in bat colonies, as well as to assess their potential threat to public health.
- MeSH
- Chiroptera * virologie MeSH
- fylogeneze MeSH
- genom virový MeSH
- infekce viry z čeledi Rhabdoviridae * veterinární epidemiologie virologie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- Vesiculovirus * genetika izolace a purifikace klasifikace MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Středomoří MeSH
UNLABELLED: We investigated the tripartite interactions between two intracellular bacterial symbionts, Cardinium and Wolbachia in Tyrophagus putrescentiae. Cultures of Tyrophagus putrescentiae are typically single-infected by one intracellular symbiont. However, co-infection can be experimentally induced by mixing single-infected cultures, resulting in 10% of mite individuals being double-infected (Cardinium + Wolbachia) and a corresponding reduction in host fitness. Here, we assembled the genomes of Cardinium and Wolbachia and analyzed their gene expression in parental single-infected and mixed mite cultures using population-level samples (ranging from 7,500 to 10,000 mites). Wolbachia interacts more extensively with its mite host than Cardinium in single-infected cultures. However, in mixed cultures, (i) Wolbachia exhibited reduced regulation of the host compared with Cardinium; (ii) the gene expression profile of Cardinium shifted, increasing its interactions with the host, whereas the gene expression profile of Wolbachia remained unchanged; and (iii) Wolbachia genes exhibited a loss of interactions with mite gene expression, as indicated by reduced correlations (for example with host MAPK, endocytosis, and calcium signaling pathways). The experiments show that at the mite population level, symbiont infection disrupts gene expression interaction between the two symbionts and their host in different ways. Wolbachia was more influenced by Cardinium gene expression than vice versa. Cardinium can inhibit the growth of Wolbachia by disrupting its interaction with the host, leading to a loss of Wolbachia's influence on mite immune and regulatory pathways. The reasons for responses are due to co-infection or the reduced frequency of Wolbachia single-infected individuals due to the analyses of population-level samples. IMPORTANCE: We found that Cardinium disrupts the interaction between Wolbachia and mite host. In Wolbachia single-infected cultures, strong correlations exist between symbiont and host gene expressions. Interestingly, although Cardinium can also interact with the host, this interaction appears weaker compared with Wolbachia in single-infected cultures. These results suggest that both symbionts affect mite host gene expression, particularly in immune and regulatory pathways. In mixed samples, Cardinium appears to outcompete Wolbachia by disrupting its host interaction. It indicates competition between these two intracellular symbionts in mite populations. Wolbachia belongs to a mite-specific supergroup Q, distinct from the more commonly studied Wolbachia supergroups. As these mite-specific bacteria exhibit pathogen-blocking effects, our findings may have relevance for other systems, such as ticks and tick-borne diseases. The study sheds light on intracellular symbiont interaction within a novel mite-symbiont model.
- MeSH
- Bacteroidetes * fyziologie genetika MeSH
- roztoči * mikrobiologie MeSH
- symbióza MeSH
- Wolbachia * genetika fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The canonical Wnt signaling pathway controls the continuous renewal of the intestinal epithelium and the specification of epithelial cell lineages. Tcf4, a nuclear mediator of Wnt signaling, is essential for the differentiation and maintenance of Paneth cells in the small intestine. Its deficiency is associated with reduced expression of key α-defensins, highlighting its role in host-microbe interactions. However, the exact function of Tcf4 in specifying the secretory lineage and its contribution to antimicrobial peptide production remain incompletely understood. Remarkably, α-defensin expression has also been detected in human colon adenomas, where aberrant Wnt signaling is a hallmark. This raises important questions: What is the role of these Paneth-like cells in tumor biology, and how does Tcf4 influence their identity and function? METHODS: We investigated cell specification in small intestinal crypts and colon tumors using conditional Tcf7l2 deletion, cell type-specific Cre recombinases, and reporter alleles in mice. Transcriptomic (single-cell and bulk RNA sequencing) and histological analyses were performed and complemented by microbiome profiling, antibiotic treatment, and intestinal organoids to functionally validate the main findings. RESULTS: The inactivation of Tcf4 depletes Paneth cells and antimicrobial peptides, disrupting the gut microbiota balance. In secretory progenitors, loss of Tcf4 shifts differentiation toward goblet cells. In the small intestine, alternative secretory progenitors produce Wnt ligands to support stem cells and epithelial renewal in the absence of Paneth cells. In colon tumors, Paneth-like cells form a tumor cell population, express Wnt ligands, and require Tcf4 for their identity. Loss of Tcf4 redirects their differentiation toward goblet cells. CONCLUSIONS: Tcf4 controls the balance between Paneth and goblet cells and is essential for antimicrobial peptide production in the small intestine. In colon adenomas, Paneth-like tumor cells drive antimicrobial gene expression and provide Wnt3 ligands, which may have implications for cancer therapy.
- MeSH
- alfa-defensiny metabolismus MeSH
- buněčná diferenciace MeSH
- lidé MeSH
- myši MeSH
- nádory tračníku * patologie genetika mikrobiologie metabolismus MeSH
- organoidy metabolismus MeSH
- Panethovy buňky metabolismus MeSH
- pohárkové buňky metabolismus MeSH
- signální dráha Wnt MeSH
- střevní mikroflóra * MeSH
- tenké střevo * metabolismus patologie mikrobiologie MeSH
- transkripční faktor 4 * metabolismus genetika MeSH
- transkriptom * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Klebsiella pneumoniae, a Gram-negative bacterium, comprises strains with diverse virulence potentials, ranging from classical to hypervirulent variants. Understanding the genetic basis underlying the virulence disparities between hypervirulent (hvKp) and classical K. pneumoniae (cKp) strains is crucial. hvKp strains are characterized by hypermucoviscosity, attributed to the presence of specific virulence genes and the production of molecules that aid in their ability to survive, evade host immune defenses, and cause infection. In contrast, classical strains exhibit a broader array of antimicrobial resistance determinants, conferring resistance to multiple antibiotics. Although current definitions of hvKp incorporate clinical features, phenotypes, and genotypes, identifying hvKp strains in clinical settings remains challenging. Genomic studies have been pivotal and have helped to identify distinct genetic profiles in hvKp strains, including unique virulence plasmids and chromosomal variations, underscoring the genetic diversity within K. pneumoniae populations. This review examines the virulence and genetic determinants associated with hvKp. The presence of genes defining hypervirulence, alongside considerations of their utility as biomarkers and targets for therapeutic strategies, is discussed, while also providing insight into biofilm formation by hvKp and key questions that need urgent responses in understanding hvKp.
- MeSH
- antibakteriální látky farmakologie MeSH
- biofilmy růst a vývoj MeSH
- faktory virulence * genetika MeSH
- infekce bakteriemi rodu Klebsiella * mikrobiologie MeSH
- Klebsiella pneumoniae * patogenita genetika účinky léků MeSH
- lidé MeSH
- virulence genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Heteropágy alebo parazitické zrastené dvojčatá predstavujú extrémne zriedkavú anomáliu, ktorá sa vyskytuje približne v 1 z 1 milióna prípadov. Sú charakterizované prítomnosťou parazitického dvojčaťa s významnou vrodenou abnormalitou, pripojeného k zvyčajne inak zdravému plodu. Dobre vyvinuté dvojča je známe ako „autosite“ alebo „hostiteľ“, zatiaľ čo ťažko postihnutý plod sa nazýva „parazit“. Prežitie defektného dvojčaťa závisí od kardiovaskulárneho systému druhého, relatívne normálneho plodu. Predstavujeme prípad 27-ročnej primigravidy v 14. týždni gravidity s ultrazvukovým nálezom poukazujúcim na parazitické zrastené dvojčatá, omfalopágy.
Heteropagus or parasitic conjoined twins represent an extremely rare anomaly, occurring in approximately 1 in 1 million cases. This condition is characterized by the presence of a parasitic twin with significant congenital abnormalities attached to an otherwise typically healthy fetus. The well-developed twin is known as the “autosite” or “host,” while the severely affected fetus is termed the “parasite.” Survival of the defective twin depends on the cardiovascular system of the second, relatively normal fetus. We present the case of a 27-year-old primigravida in her 14th week of pregnancy with ultrasound findings indicating parasitic conjoined twins, specifically omphalopagus.
- MeSH
- dospělí MeSH
- fetus in fetu * diagnóza MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- monstra duplicia * MeSH
- prenatální diagnóza MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The gut microbiota has recently come to the forefront of scientific interest, particularly due to its broad spectrum of action not only on tissues that it comes into direct contact with, but also - through a variety of agents - on distant tissues and organs. There are a number of previously described mechanisms through which gut-colonizing microorganisms can affect the host's immune or endocrine systems as well as the central nervous system and behaviour of the host. A number of research teams are studying the microbiome in relation to neurological diseases, investigating the possible effect of specific microorganisms and microbial metabolites on the development and progression of these diseases. This publication deals with those diseases that have been most widely studied and described in this context.
- MeSH
- Alzheimerova nemoc diagnóza etiologie MeSH
- lidé MeSH
- osa mozek-střevo * fyziologie genetika MeSH
- parkinsonské poruchy diagnóza etiologie MeSH
- poruchy autistického spektra diagnóza etiologie genetika MeSH
- roztroušená skleróza diagnóza etiologie MeSH
- střevní mikroflóra * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Ticks are important vectors of various microorganisms, including bacteria. In this study, we examined Hyalomma aegyptium ticks collected from 240 spur-thighed tortoises Testudo graeca at 42 localities in the Mediterranean and Middle East and analysed them for the presence of bacteria of the genera Anaplasma, Borrelia, Coxiella, and Rickettsia. Altogether, 576 out of 928 analysed ticks (62.1%) were positive for at least one of the tested bacteria. The highest prevalence in individual ticks was found for Borrelia turcica (43.6%), followed by Rickettsia (12.3%) and Anaplasma (6.1%). No sample was positive for Coxiella burnetii. Among Rickettsia, we detected two species, Rickettsia africae and Rickettsia aeschlimannii, and also other unspecified Rickettsia. Anaplasma (100% identity with A. phagocytophilum) was detected at 15 (35%) out of 42 studied localities, any of Rickettsia at 28 (67%), and B. turcica at 32 (76%) localities. The geographic distribution of the studied microorganisms varied, with none of them detected in Syria, and only Rickettsia spp. detected in Morocco. Sequence analysis revealed substantial genetic variability in all detected agents, with the most variable (36 new haplotypes) being glpQ gene used as a marker for B. turcica. We also analysed the prevalence of various co-infections among studied ticks, with the mean number of co-infected ticks per tortoise increased with the number of ticks per tortoise. However, the frequencies of co-infected ticks do not indicate the presence of antagonistic or synergistic facilitative interactions between the agents. According to our data, we could expect that the eco-epidemiological importance of H. aegyptium does not stem from their tortoise hosts but rather from the low host specificity of its larvae and nymphs, feeding on a wider spectrum of reptilian, avian, and mammalian hosts.
- MeSH
- Anaplasma * izolace a purifikace MeSH
- Borrelia izolace a purifikace MeSH
- Coxiella izolace a purifikace genetika MeSH
- infestace klíšťaty veterinární epidemiologie parazitologie MeSH
- Ixodidae * mikrobiologie růst a vývoj MeSH
- Rickettsia * izolace a purifikace MeSH
- želvy * mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Střední východ MeSH
- Středomoří MeSH
We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD. Myeloablative conditioning was used in 930 patients (51%), while 1130 (62%) received an intensified conditioning (score ≥2.5) based on the transplant conditioning intensity (TCI) score. Conditioning intensity using the myeloablative/reduced intensity stratification did not impact transplant outcomes across the entire cohort. However, a higher TCI score was associated with a lower risk of relapse, with no effect on survival. In specific cytogenetic risk groups, a higher TCI score did not influence outcomes in the adverse-risk group. In the intermediate-risk group, the impact varied with FLT3-ITD status. Patients with FLT3-ITD mutation who received a higher TCI showed a beneficial effect on relapse, leukemia-free survival (LFS), and overall survival. Conversely, in FLT3-ITD wild-type patients, more intense conditioning had a detrimental effect on graft-versus-host disease-free, and relapse-free survival with no effect on other outcomes. In conclusion, for AML patients in CR1 undergoing HSCT with PTCy, it is crucial to consider cytogenetic risk and molecular status when selecting the conditioning regimen. Intensive conditioning should be considered for patients with intermediate-risk cytogenetics and mutated FLT3-ITD but should probably be avoided for those with wild-type FLT3-ITD.
- MeSH
- akutní myeloidní leukemie * terapie genetika mortalita MeSH
- cyklofosfamid * terapeutické užití aplikace a dávkování farmakologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- příprava pacienta k transplantaci * metody MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH