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Systematic Biology Aug 2023Accurate phylogenies are fundamental to our understanding of the pattern and process of evolution. Yet, phylogenies at deep evolutionary timescales, with correspondingly...
Accurate phylogenies are fundamental to our understanding of the pattern and process of evolution. Yet, phylogenies at deep evolutionary timescales, with correspondingly long branches, have been fraught with controversy resulting from conflicting estimates from models with varying complexity and goodness of fit. Analyses of historical as well as current empirical datasets, such as alignments including Microsporidia, Nematoda, or Platyhelminthes, have demonstrated that inadequate modeling of across-site compositional heterogeneity, which is the result of biochemical constraints that lead to varying patterns of accepted amino acids along sequences, can lead to erroneous topologies that are strongly supported. Unfortunately, models that adequately account for across-site compositional heterogeneity remain computationally challenging or intractable for an increasing fraction of contemporary datasets. Here, we introduce "compositional constraint analysis," a method to investigate the effect of site-specific constraints on amino acid composition on phylogenetic inference. We show that more constrained sites with lower diversity and less constrained sites with higher diversity exhibit ostensibly conflicting signals under models ignoring across-site compositional heterogeneity that lead to long-branch attraction artifacts and demonstrate that more complex models accounting for across-site compositional heterogeneity can ameliorate this bias. We present CAT-posterior mean site frequencies (PMSF), a pipeline for diagnosing and resolving phylogenetic bias resulting from inadequate modeling of across-site compositional heterogeneity based on the CAT model. CAT-PMSF is robust against long-branch attraction in all alignments we have examined. We suggest using CAT-PMSF when convergence of the CAT model cannot be assured. We find evidence that compositionally constrained sites are driving long-branch attraction in two metazoan datasets and recover evidence for Porifera as the sister group to all other animals. [Animal phylogeny; cross-site heterogeneity; long-branch attraction; phylogenomics.].
Topics: Animals; Phylogeny; Bias; Microsporidia; Models, Genetic
PubMed: 36946562
DOI: 10.1093/sysbio/syad013 -
PLoS Pathogens Dec 2023Microsporidia are a group of obligate intracellular parasites that infect almost all animals, causing serious human diseases and major economic losses to the farming...
Microsporidia are a group of obligate intracellular parasites that infect almost all animals, causing serious human diseases and major economic losses to the farming industry. Nosema bombycis is a typical microsporidium that infects multiple lepidopteran insects via fecal-oral and transovarial transmission (TOT); however, the underlying TOT processes and mechanisms remain unknown. Here, we characterized the TOT process and identified key factors enabling N. bombycis to invade the ovariole and oocyte of silkworm Bombyx mori. We found that the parasites commenced with TOT at the early pupal stage when ovarioles penetrated the ovary wall and were exposed to the hemolymph. Subsequently, the parasites in hemolymph and hemolymph cells firstly infiltrated the ovariole sheath, from where they invaded the oocyte via two routes: (I) infecting follicular cells, thereby penetrating oocytes after proliferation, and (II) infecting nurse cells, thus entering oocytes following replication. In follicle and nurse cells, the parasites restructured and built large vacuoles to deliver themselves into the oocyte. In the whole process, the parasites were coated with B. mori vitellogenin (BmVg) on their surfaces. To investigate the BmVg effects on TOT, we suppressed its expression and found a dramatic decrease of pathogen load in both ovarioles and eggs, suggesting that BmVg plays a crucial role in the TOT. Thereby, we identified the BmVg domains and parasite spore wall proteins (SWPs) mediating the interaction, and demonstrated that the von Willebrand domain (VWD) interacted with SWP12, SWP26 and SWP30, and the unknown function domain (DUF1943) bound with the SWP30. When disrupting these interactions, we found significant reductions of the pathogen load in both ovarioles and eggs, suggesting that the interplays between BmVg and SWPs were vital for the TOT. In conclusion, our study has elucidated key aspects about the microsporidian TOT and revealed the key factors for understanding the molecular mechanisms underlying this transmission.
Topics: Animals; Humans; Vitellogenins; Spores, Fungal; Nosema; Bombyx
PubMed: 38060601
DOI: 10.1371/journal.ppat.1011859 -
Microbiology Spectrum Dec 2023There are a few reports on the resistance of microsporidia, including . Here, the alkali-soluble germination proteins of were used as immunogens to prepare a monoclonal...
There are a few reports on the resistance of microsporidia, including . Here, the alkali-soluble germination proteins of were used as immunogens to prepare a monoclonal antibody, and its single-chain variable fragments effectively blocked microsporidia infection. Our study has provided novel strategies for microsporidiosis control and demonstrated a useful method for the potential treatment of other microsporidia diseases.
Topics: Animals; Bombyx; Nosema; Microsporidiosis; Antibodies, Monoclonal; Spores; Cell Proliferation
PubMed: 37811955
DOI: 10.1128/spectrum.00681-23 -
Transactions of the Royal Society of... Apr 2024Microsporidia and Cryptosporidium are obligate intracellular protozoa. These medically important species are recognized as opportunistic organisms in intestinal...
BACKGROUND
Microsporidia and Cryptosporidium are obligate intracellular protozoa. These medically important species are recognized as opportunistic organisms in intestinal complications in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients.
METHODS
The current cross-sectional study was designed and conducted from August 2016 to August 2017 to determine intestinal Cryptosporidium and microsporidia spp. in HIV-infected individuals from the Behavioral Diseases Counseling Center, Tabriz, Iran, by modified acid-fast and modified trichrome staining and nested polymerase chain reaction (PCR) and real-time PCR.
RESULTS
Of 100 HIV-infected persons, 21.0% (95% confidence interval [CI] 13.0 to 30.0) and 18.0% (95% CI 11.0 to 26.0) were identified as Cryptosporidium and microsporidia, respectively, by the microscopic method. Of these 100 HIV-infected persons, 18.0% (95% CI 11.0 to 26.0) and 14.0% (95% CI 7.0 to 22.0) were positive for Cryptosporidium and microsporidia, respectively, by the molecular method. The predominant species of microsporidia in patients was Enterocytozoon bieneusi (85.7% [95% CI 57.0 to 98.0]) and Encephalitozoon cuniculi (14.3% [95% CI 1.7 to 42.0]), which were found by quantitative real-time PCR and its high-resolution melting tool.
CONCLUSIONS
As far as we know, this study is the first to estimate the prevalence of infection with Cryptosporidium and microsporidia among HIV-infected persons in northwest of Iran. The prevalence of intestinal microsporidiosis and cryptosporidiosis in this area in HIV-infected people was higher than the global prevalence of infection among immunocompromised patients. In addition to the need for further studies to prove protozoan pathogenicity in the aforementioned group, preventive measures should be considered.
Topics: Humans; Cryptosporidium; Cryptosporidiosis; HIV; Prevalence; Cross-Sectional Studies; Microsporidiosis; Microsporidia; HIV Infections; Real-Time Polymerase Chain Reaction; Feces
PubMed: 38141032
DOI: 10.1093/trstmh/trad090 -
The Veterinary Record Jul 2023There is a relative paucity of data examining the prevalence of renal pathology in wild rabbits.
BACKGROUND
There is a relative paucity of data examining the prevalence of renal pathology in wild rabbits.
METHODS
Sixty-two wild rabbits that had been shot for population control in Cambridgeshire, UK, underwent postmortem examination, including macroscopic and microscopic renal assessment.
RESULTS
The majority (82%) of the animals had macroscopically and microscopically normal kidneys. One animal (1.6%) had severe perirenal abscessation. Pasteurella spp. was isolated from this lesion. Ten rabbits (16%) had microscopic renal pathology comprising minimal to mild renal inflammation or fibrosis. No Encephalitozoon cuniculi organisms were detected histologically.
LIMITATIONS
The sample population was composed of shot rabbits, so the probability of detecting moribund individuals was reduced. Extrapolation of these data to the wider UK wild rabbit population may be limited as rabbits were shot at two sites within a 3 km radius of each other.
CONCLUSION
Renal pathology is rare in the population examined.
Topics: Animals; Rabbits; Kidney; Encephalitozoon cuniculi; Brain; Encephalitozoonosis
PubMed: 37095703
DOI: 10.1002/vetr.2948 -
PLoS Neglected Tropical Diseases Dec 2023Microsporidia are fungal obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to...
Microsporidia are fungal obligate intracellular pathogens, which infect most animals and cause microsporidiosis. Despite the serious threat that microsporidia pose to humans and agricultural animals, few drugs are available for the treatment and control of microsporidia. To identify novel inhibitors, we took advantage of the model organism Caenorhabditis elegans infected with its natural microsporidian Nematocida parisii. We used this system to screen the Pandemic Response Box, a collection of 400 diverse compounds with known antimicrobial activity. After testing these compounds in a 96-well format at high (100 μM) and low (40 μM) concentrations, we identified four inhibitors that restored the ability of C. elegans to produce progeny in the presence of N. parisii. All four compounds reduced the pathogen load of both N. parisii and Pancytospora epiphaga, a C. elegans-infecting microsporidia related to human-infecting species. One of these compounds, a known inhibitor of a viral protease, MMV1006203, inhibited invasion and prevented the firing of spores. A bis-indole derivative, MMV1593539, decreased spore viability. An albendazole analog, MMV1782387, inhibited proliferation of N. parisii. We tested albendazole as well as 5 other analogs and observed that MMV1782387 was amongst the strongest inhibitors of N. parisii and displayed the least host toxicity. Our study further demonstrates the effectiveness of the C. elegans-N. parisii system for discovering microsporidia inhibitors and the compounds we identified provide potential scaffolds for anti-microsporidia drug development.
Topics: Animals; Humans; Caenorhabditis elegans; Albendazole; Pandemics; Microsporidia; Microsporidiosis
PubMed: 38064503
DOI: 10.1371/journal.pntd.0011806 -
Parasites & Vectors Aug 2023Microsporidia are a class of obligate intracellular parasitic unicellular eukaryotes that infect a variety of hosts, even including humans. Although different species of... (Review)
Review
Microsporidia are a class of obligate intracellular parasitic unicellular eukaryotes that infect a variety of hosts, even including humans. Although different species of microsporidia differ in host range and specificity, they all share a similar infection organelle, the polar tube, which is also defined as the polar filament in mature spores. In response to the appropriate environmental stimulation, the spore germinates with the polar filament everted, forming a hollow polar tube, and then the infectious cargo is transported into host cells via the polar tube. Hence, the polar tube plays a key role in microsporidian infection. Here, we review the origin, structure, composition, function, and application of the microsporidian polar tube, focusing on the origin of the polar filament, the structural differences between the polar filament and polar tube, and the characteristics of polar tube proteins. Comparing the three-dimensional structure of PTP6 homologous proteins provides new insight for the screening of additional novel polar tube proteins with low sequence similarity in microsporidia. In addition, the interaction of the polar tube with the spore wall and the host are summarized to better understand the infection mechanism of microsporidia. Due to the specificity of polar tube proteins, they are also used as the target in the diagnosis and prevention of microsporidiosis. With the present findings, we propose a future study on the polar tube of microsporidia.
Topics: Humans; Microsporidia; Microsporidiosis; Biological Transport; Cell Wall; Cytoskeleton
PubMed: 37649053
DOI: 10.1186/s13071-023-05908-9 -
Parasites & Vectors Sep 2023The demonstration that the recently discovered Anopheles symbiont Microsporidia MB blocks malaria transmission in Anopheles arabiensis and undergoes vertical and...
BACKGROUND
The demonstration that the recently discovered Anopheles symbiont Microsporidia MB blocks malaria transmission in Anopheles arabiensis and undergoes vertical and horizontal transmission suggests that it is a promising candidate for the development of a symbiont-based malaria transmission-blocking strategy. The infection prevalence and characteristics of Microsporidia MB in Anopheles gambiae sensu stricto (s.s.), another primary vector species of malaria in Kenya, were investigated.
METHODS
Field-collected females were confirmed to be Microsporidia MB-positive after oviposition. Egg counts of Microsporidia MB-infected and non-infected individuals were used to infer the effects of Microsporidia MB on fecundity. The time to pupation, adult sex ratio and survival were used to determine if Microsporidia MB infection has similar characteristics in the host mosquitoes An. gambiae and An. arabiensis. The intensity of Microsporidia MB infection in tissues of the midgut and gonads, and in carcasses, was determined by quantitative polymerase chain reaction. To investigate horizontal transmission, virgin males and females that were either Microsporidia MB-infected or non-infected were placed in standard cages for 48 h and allowed to mate; transmission was confirmed by quantitative polymerase chain reaction targeting Microsporidia MB genes.
RESULTS
Microsporidia MB was found to naturally occur at a low prevalence in An. gambiae s.s. collected in western Kenya. Microsporidia MB shortened the development time from larva to pupa, but other fitness parameters such as fecundity, sex ratio, and adult survival did not differ between Microsporidia MB-infected and non-infected hosts. Microsporidia MB intensities were high in the male gonadal tissues. Transmission experiments indicated that Microsporidia MB undergoes both maternal and horizontal transmission in An. gambiae s.s.
CONCLUSIONS
The findings that Microsporidia MB naturally infects, undergoes maternal and horizontal transmission, and is avirulent in An. gambiae s.s. indicate that many of the characteristics of its infection in An. arabiensis hold true for the former. The results of the present study indicate that Microsporidia MB could be developed as a tool for the transmission-blocking of malaria across different Anopheles species.
Topics: Humans; Animals; Female; Male; Malaria; Anopheles; Mosquito Vectors; Microsporidia; Insect Vectors
PubMed: 37749577
DOI: 10.1186/s13071-023-05933-8 -
Parasites & Vectors Jan 2024Malaria, a disease transmitted by Anopheles mosquitoes, is a major public health problem causing millions of deaths worldwide, mostly among children under the age of 5...
BACKGROUND
Malaria, a disease transmitted by Anopheles mosquitoes, is a major public health problem causing millions of deaths worldwide, mostly among children under the age of 5 years. Biotechnological interventions targeting parasite-vector interactions have shown that the microsporidian symbiont Microsporidia MB has the potential to disrupt and block Plasmodium transmission.
METHODS
A prospective cross-sectional survey was conducted in Zinder City (Zinder), Niger, from August to September 2022, using the CDC light trap technique to collect adult mosquitoes belonging to the Anopheles gambiae complex. The survey focused on collecting mosquitoes from three neighborhoods of Zinder (Birni, Kangna and Garin Malan, located in communes I, II and IV, respectively). Collected mosquitoes were sorted and preserved in 70% ethanol. PCR was used to identify host species and detect the presence of Microsporidia MB and Plasmodium falciparum infection.
RESULTS
Of the 257 Anopheles mosquitoes collected and identified by PCR, Anopheles coluzzii was the most prevalent species, accounting for 97.7% of the total. Microsporidia MB was exclusively detected in A. coluzzii, with a prevalence of 6.8% (17/251) among the samples. No significant difference in prevalence was found among the three neighborhoods. Only one An. coluzzii mosquito tested PCR-positive for P. falciparum.
CONCLUSIONS
The results confirm the presence of Microsporidia MB in Anopheles mosquitoes in Zinder, Niger, indicating its potential use as a biotechnological intervention against malaria transmission. However, further studies are needed to determine the efficacy of Microsporidia MB to disrupt Plasmodium transmission as well as its impact on vector fitness.
Topics: Animals; Child; Humans; Child, Preschool; Anopheles; Plasmodium falciparum; Microsporidia; Niger; Cross-Sectional Studies; Prospective Studies; Mosquito Vectors; Malaria, Falciparum; Malaria; Plasmodium; Asteraceae
PubMed: 38287334
DOI: 10.1186/s13071-023-06059-7 -
Nature Microbiology Oct 2023
Topics: Microsporidia; Spores, Fungal; Microsporidiosis; Ribosomes
PubMed: 37709901
DOI: 10.1038/s41564-023-01481-0