Database : MEDLINE
Search on : Cryptosporidiosis [Words]
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[PMID]: 29522315
[Au] Autor:Vidadala RSR; Golkowski M; Hulverson MA; Choi R; McCloskey MC; Whitman GR; Huang W; Arnold SLM; Barrett LK; Fan E; Merritt EA; Van Voorhis WC; Ojo KK; Maly DJ
[Ti] Title:7H-pyrrolo[2,3-d]pyrimidin-4-amine based inhibitors of calcium dependent protein kinase 1 have distinct inhibitory and oral pharmacokinetic characteristics compared with 1H-pyrazolo[3,4-d]pyrimidin-4-amine based inhibitors.
[So] Source:ACS Infect Dis;, 2018 Mar 09.
[Is] ISSN:2373-8227
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Selective inhibitors of Cryptosporidium Calcium-Dependent Protein Kinase 1 (CpCDPK1) based on the 1H-pyrazolo[3,4-d]pyrimidin-4-amine (pyrazolopyrimidine, PP) scaffold are effective in both in vitro and in vivo models of cryptosporidiosis. However, the search for distinct safety and pharmacokinetic (PK) properties has motivated our exploration of alternative scaffolds. Here, we describe a series of 7H-pyrrolo[2,3-d]pyrimidin-4-amine (pyrrolopyrimidine, PrP)-based analogs of PP CpCDPK1 inhibitors. Most of the PrP-based inhibitors described potently inhibit the CpCDPK1 enzyme, demonstrate no toxicity against mammalian cells, and block proliferation of the C. parvum parasite in the low micromolar range. Interestingly, certain substituents that show reduced CpCDPK1 potency when displayed from a PP scaffold provided notably enhanced efficacy in the context of a PrP scaffold. PK studies on these paired compounds show that some PrP analogs have distinct physiochemical properties compared with their PP counterparts. These results demonstrate that inhibitors based on a PrP scaffold are distinct therapeutic alternatives to previously developed PP inhibitors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1021/acsinfecdis.7b00224

  2 / 5689 MEDLINE  
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[PMID]: 29518449
[Au] Autor:Lebbad M; Winiecka-Krusnell J; Insulander M; Beser J
[Ad] Address:Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
[Ti] Title:Molecular characterization and epidemiological investigation of Cryptosporidium hominis IkA18G1 and C. hominis monkey genotype IiA17, two unusual subtypes diagnosed in Swedish patients.
[So] Source:Exp Parasitol;, 2018 Mar 05.
[Is] ISSN:1090-2449
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Cryptosporidium hominis is considered a strictly human-adapted species, and it is only occasionally diagnosed in animals. However, two variants, C. hominis monkey genotype and C. hominis Ik, were originally described in non-human hosts, monkeys and horses, respectively. During a Swedish national Cryptosporidium study, where all samples were analyzed at the small subunit rRNA and the 60 kDa (gp60) glycoprotein loci, we identified two patients infected with C. hominis monkey genotype (subtype IiA17) and two infected with C. hominis subtype IkA18G1. The isolates were further analyzed at the actin and the 70 kDa heat shock protein loci, and these analyses showed that these two subtype families are closely related to each other and to human-adapted C. hominis as well as to Cryptosporidium cuniculus. The two patients with C. hominis monkey genotype infection (a father and son) had visited a monkey farm in Thailand prior to infection, while the two cases with C. hominis Ik were unrelated, both probably infected in Sweden. This is the first time that a monkey genotype infection in humans has been related to contact with monkeys and where the gp60 subtype was identified. It is also the first time that human infection caused by C. hominis subtype Ik is described. Even though we were not able to detect any parasites in the animal samples, zoonotic transmission cannot be ruled out in any of these cases because both subtype families are regarded as animal adapted.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher

  3 / 5689 MEDLINE  
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[PMID]: 29438669
[Au] Autor:Ming Z; Gong AY; Wang Y; Zhang XT; Li M; Li Y; Pang J; Dong S; Strauss-Soukup JK; Chen XM
[Ad] Address:Department of Medical Parasitology, School of Basic Medical Sciences, Wuhan University, Hubei, China; Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, United States.
[Ti] Title:Trans-suppression of host CDH3 and LOXL4 genes during Cryptosporidium parvum infection involves nuclear delivery of parasite Cdg7_FLc_1000 RNA.
[So] Source:Int J Parasitol;, 2018 Feb 10.
[Is] ISSN:1879-0135
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Intestinal infection by Cryptosporidium parvum causes significant alterations in the gene expression profile in host epithelial cells. Previous studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of human intestinal cryptosporidiosis, we report here that trans-suppression of the cadherin 3 (CDH3) and lysyl oxidase like 4 (LOXL4) genes in human intestinal epithelial cells following C. parvum infection involves host delivery of the Cdg7_FLc_1000 RNA, a C. parvum RNA that has been previously demonstrated to be delivered into the nuclei of infected host cells. Downregulation of CDH3 and LOXL4 genes was detected in host epithelial cells following C. parvum infection or in cells expressing the parasite Cdg7_FLc_1000 RNA. Knockdown of Cdg7_FLc_1000 attenuated the trans-suppression of CDH3 and LOXL4 genes in host cells induced by infection. Interestingly, Cdg7_FLc_1000 was detected to be recruited to the promoter regions of both CDH3 and LOXL4 gene loci in host cells following C. parvum infection. Host delivery of Cdg7_FLc_1000 promoted the PH domain zinc finger protein 1 (PRDM1)-mediated H3K9 methylation associated with trans-suppression in the CDH3 gene locus, but not the LOXL4 gene. Therefore, our data suggest that host delivery of Cdg7_FLc_1000 causes CDH3 trans-suppression in human intestinal epithelial cells following C. parvum infection through PRDM1-mediated H3K9 methylation in the CDH3 gene locus, whereas Cdg7_FLc_1000 induces trans-suppression of the host LOXL4 gene through H3K9/H3K27 methylation-independent mechanisms.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  4 / 5689 MEDLINE  
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[PMID]: 29514308
[Au] Autor:Gilchrist CA; Cotton JA; Burkey C; Arju T; Gilmartin A; Lin Y; Ahmed E; Steiner K; Alam M; Ahmed S; Robinson G; Zaman SU; Kabir M; Sanders M; Chalmers RM; Ahmed T; Ma JZ; Haque R; Faruque ASG; Berriman M; Petri WA
[Ad] Address:Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
[Ti] Title:Genetic diversity of Cryptosporidium hominis in a Bangladeshi community as revealed by whole genome sequencing.
[So] Source:J Infect Dis;, 2018 Mar 05.
[Is] ISSN:1537-6613
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We studied the genetic diversity of Cryptosporidium hominis infections in slum dwelling infants from Dhaka over a two-year period. C. hominis infections were common during the monsoon, and were genetically diverse as measured by gp60 genotyping and whole genome resequencing. Recombination in the parasite was evidenced by the decay of linkage disequilibrium in the genome over less than 300 bp. Regions of the genome with high levels of polymorphism were also identified.  Yet to be determined is if genomic diversity is responsible in part for the high rate of reinfection, seasonality and varied clinical presentations of cryptosporidiosis in this population.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:Publisher
[do] DOI:10.1093/infdis/jiy121

  5 / 5689 MEDLINE  
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[PMID]: 29514125
[Au] Autor:Martins TA; Seixas M; Brito DRB; Martins FDC; Cardim ST; Melo P; da Paixão Guterres SF; Patrício EG; Garcia JL
[Ad] Address:Protozoology Laboratory, Departamento de Medicina Veterinária Preventiva, Universidade Estadual de Londrina - UEL, Postal Box 6001, 86050-970 Londrina, PR, Brazil.
[Ti] Title:First identification of Cryptosporidium parvum subtype IIaA20G1R1 in water buffalos (Bubalus bubalis).
[So] Source:Res Vet Sci;118:181-183, 2018 Mar 04.
[Is] ISSN:1532-2661
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Cryptosporidium can infect a wide variety of vertebrate animals, including mammals, birds, amphibians, reptiles, and fish. There are few molecular characterizations of Cryptosporidium isolated from water buffalo. Thus, the present study investigated the occurrence and molecular characterization of Cryptosporidium spp. in water buffalos by nested-PCR. Non-diarrheic feces were obtained from 122 water buffalo calves. All samples were tested by nested-PCR based on the 18S rRNA gene, after which positive samples were analyzed by RFLP and genetic sequencing. Sixteen fecal (13.1%) samples were positive, and RFLP showed that fifteen presented patterns consistent with C. ryanae and one with C. parvum. Sequencing of the gp60 gene from the C. parvum positive sample indicated the subtype IIaA20G1R1. This is the first identification of the IIaA20G1R1 subtype in water buffalos.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:Publisher

  6 / 5689 MEDLINE  
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[PMID]: 29300993
[Au] Autor:Guo F; Zhang H; McNair NN; Mead JR; Zhu G
[Ad] Address:Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas.
[Ti] Title:The existing drug vorinostat as a new lead against cryptosporidiosis by targeting the parasite histone deacetylases.
[So] Source:J Infect Dis;, 2018 Jan 02.
[Is] ISSN:1537-6613
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Background: Cryptosporidiosis affects all human populations, but can be much more severe or life-threatening in children and individuals with weak or weakened immune systems. However, current options to treat cryptosporidiosis are limited. Methods: An in vitro phenotypic screening assay was employed to screen 1,200 existing drugs for their anti-cryptosporidial activity, and to determine the inhibitory kinetics of top hits. Selected top hits were further evaluated in mice. The action of the lead compound vorinostat on the parasite histone deacetylase (HDAC) was biochemically validated. Results: Fifteen (15) compounds exhibited anti-cryptosporidial activity at nanomolar level in vitro. Among them, the histone deacetylase (HDAC) inhibitor vorinostat retained outstanding efficacy in vitro (EC50 = 203 nM) and in IL-12 knockout mouse model (ID50 = 7.5 mg/kg). Vorinostat was effective on various parasite developmental stages, and could irreversibly kill the parasite. Vorinostat was highly effective against the parasite native HDAC enzymes (IC50 = 90.0 nM) and a recombinant C. parvum HDAC (Ki = 123.0 nM). Conclusion: These findings suggest the potential for repurposing of vorinostat to treat cryptosporidiosis, and imply that the parasite HDAC can be explored for developing more selective anti-cryptosporidial therapeutics.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1093/infdis/jix689

  7 / 5689 MEDLINE  
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[PMID]: 29501402
[Au] Autor:Sahimin N; Douadi B; Lim YAL; Behnke JM; Zain SNM
[Ad] Address:Institute of Biological Science, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
[Ti] Title:Distribution of Giardia duodenalis (Assemblages A and B) and Cryptosporidium parvum amongst migrant workers in Peninsular Malaysia.
[So] Source:Acta Trop;, 2018 Mar 01.
[Is] ISSN:1873-6254
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The influx of low skilled workers from socioeconomically deprived neighbouring countries to Malaysia has raised concerns about the transmission of communicable gastrointestinal diseases such as giardiasis and cryptosporidiosis to the local population. Therefore, a cross sectional study was conducted to investigate the prevalence of both diseases and the genetic diversity of these pathogens in the migrant population. Microscopic examination of faecal samples from 388 migrant workers involved in five working sectors were screened and 10.8% (n = 42) were found to be positive with Giardia spp. and 3.1% (n = 12) with Cryptosporidium spp. infections. PCR amplicons at the triosephosphate isomerase (tpi) gene were successfully obtained for Giardia duodenalis from 30 (30/388; 7.73%) samples with assemblages AII and B in 13 (13/30; 43.3%) and 17 (17/30; 56.7%) positive samples, respectively. Nine samples (9/388; 2.3%) were identified as Cryptosporidium parvum using PCR-RFLP analysis. Country of origin, duration of residence in Malaysia and working sectors significantly influenced G. duodenalis assemblage AII infections amongst the targeted population. Meanwhile, C. parvum infection was significantly associated with those working in the food service sector. Despite the low presence of pathogenic G. duodenalis and C. parvum in the study population, the results highlight the risk of anthroponotic foodborne and waterborne transmission and therefore call for implementation of control strategies through improvements in personal hygiene and sanitation standards.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:Publisher

  8 / 5689 MEDLINE  
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[PMID]: 29411108
[Au] Autor:Velásquez JN; Pantano ML; Vittar N; Nigro MG; Figueiras O; Astudillo OG; Ricart J; Della Paolera D; Carnevale S
[Ad] Address:Hospital Municipal de Infecciosas "Dr. Francisco Javier Muñiz", Buenos Aires, Argentina. jorgeysilvana@speedy.com.ar.
[Ti] Title:First detection of Cryptosporidium DNA in blood and cerebrospinal fluid of HIV-infected patients.
[So] Source:Parasitol Res;117(3):875-881, 2018 Mar.
[Is] ISSN:1432-1955
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Human cryptosporidiosis is an intestinal infection caused by different species belonging to the genus Cryptosporidium in both immunocompetent and immunocompromised individuals. The life cycle of Cryptosporidium sp. when affecting the digestive system is well known but the infection of other organs is less studied. Molecular methods are necessary for species and subtypes identification. The goal of this work is to propose a new approach that contributes to the diagnosis of the extra-intestinal dissemination process of Cryptosporidium infection. Cryptosporidium sp. was detected in stool and biopsy samples of two HIV-infected patients. DNA was extracted from feces, biopsy specimens, blood, and cerebrospinal fluid (CSF). All samples were analyzed by nested PCR-RFLP of the 18S rDNA, real-time PCR, and gp60 subtyping. Cryptosporidium DNA was detected in stool and tissue samples and it was also present in blood and CSF samples. Both cases were characterized as Cryptosporidium hominis subtype IeA11G3T3. This is the first report that demonstrates the presence of Cryptosporidium DNA in blood and CSF of HIV-infected patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Process
[do] DOI:10.1007/s00436-018-5766-1

  9 / 5689 MEDLINE  
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[PMID]: 29374323
[Au] Autor:Ming Z; Gong AY; Wang Y; Zhang XT; Li M; Dolata CE; Chen XM
[Ad] Address:Department of Medical Parasitology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
[Ti] Title:Trans-suppression of defense DEFB1 gene in intestinal epithelial cells following Cryptosporidium parvum infection is associated with host delivery of parasite Cdg7_FLc_1000 RNA.
[So] Source:Parasitol Res;117(3):831-840, 2018 Mar.
[Is] ISSN:1432-1955
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:To counteract host immunity, Cryptosporidium parvum has evolved multiple strategies to suppress host antimicrobial defense. One such strategy is to reduce the production of the antimicrobial peptide beta-defensin 1 (DEFB1) by host epithelial cells but the underlying mechanisms remain unclear. Recent studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of intestinal cryptosporidiosis, in this study, we analyzed the expression profile of host beta-defensin genes in host cells following infection. We found that C. parvum infection caused a significant downregulation of the DEFB1 gene. Interestingly, downregulation of DEFB1 gene was associated with host delivery of Cdg7_FLc_1000 RNA transcript, a C. parvum RNA that has previously demonstrated to be delivered into the nuclei of infected host cells. Knockdown of Cdg7_FLc_1000 in host cells could attenuate the trans-suppression of host DEFB1 gene and decreased the parasite burden. Therefore, our data suggest that trans-suppression of DEFB1 gene in intestinal epithelial cells following C. parvum infection involves host delivery of parasite Cdg7_FLc_1000 RNA, a process that may be relevant to the epithelial defense evasion by C. parvum at the early stage of infection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Process
[do] DOI:10.1007/s00436-018-5759-0

  10 / 5689 MEDLINE  
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[PMID]: 29306010
[Au] Autor:Chelbi H; Essid R; Jelassi R; Bouzekri N; Zidi I; Ben Salah H; Mrad I; Ben Sghaier I; Abdelmalek R; Aissa S; Bouratbine A; Aoun K
[Ad] Address:LR 11-IPT-06 Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Pasteur Institute of Tunis, University Tunis El Manar, Tunisia. Electronic address: hanene.chelbi@pasteur.rns.tn.
[Ti] Title:High-resolution melting-curve (HRM) analysis for C. meleagridis identification in stool samples.
[So] Source:Microb Pathog;115:332-337, 2018 Jan 03.
[Is] ISSN:1096-1208
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Cryptosporidiosis represents a major public health problem. This infection, caused by a protozoan parasite of the genus Cryptosporidium, has been reported worldwide as a frequent cause of diarrhoea. In the immunocompetent host, the typical watery diarrhea can be self-limiting. However, it is severe and chronic, in the immunocompromised host and may cause death. Cryptosporidium spp. are coccidians, which complete their life cycle in both humans and animals. The two species C. hominis and C. parvum are the major cause of human infection. Compared to studies on C. hominis and C. parvum, only a few studies have developed methods to identify C. meleagridis. AIM: To develop a new real time PCR-coupled High resolution melting assay allowing the detection for C. meleagridis, in addition of the other dominant species (C. hominis and C. parvum). METHODS: The polymorphic sequence on the dihydrofolate reductase gene (DHFR) of three species was sequenced to design primers pair and establish a sensitive real-time PCR coupled to a high-resolution melting-curve (HRM) analysis method, allowing the detection of Cryptosporidium sp. and discrimination between three prevalent species in Tunisia. We analyzed a collection of 42 archived human isolates of the three studied species. RESULTS: Real-time PCR coupled to HRM assay allowed detection of Cryptosporidium, using the new designed primers, and basing on melting profile, we can distinguish C. meleagridis species in addition to C. parvum and C. hominis. CONCLUSION: We developed a qPCR-HRM assay that allows Cryptosporidium genotyping. This method is sensitive and able to distinguish three Cryptosporidium species.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[St] Status:Publisher


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