Dataset Information

Cryptosporidium parvum Infection Depletes Butyrate Producer Bacteria in Goat Kid Microbiome.

ABSTRACT: Cryptosporidium parvum is an important apicomplexan parasite infecting ruminants and humans. We characterized the impact of C. parvum infection on the goat kid microbiome. C. parvum was orally administered to parasite-naïve goats, and infection was monitored for 26 days in fecal samples using immunofluorescence assay and qPCR tests. Age-matched goats served as uninfected controls. A reduction in body weight gain, diarrhea, and dehydration were observed in infected goats compared to the uninfected controls. Infection decreased the bacterial diversity 5 days post-infection (dpi), but this parameter recovered at 15 dpi. The infection altered the relative abundance of several taxa. A total of 38 taxa displayed significant differences in abundance between control and infected goats at both 5 and 15 dpi. Co-occurrence network analysis revealed that the infection resulted in a differential pattern of taxa interactions and that C. parvum infection increased the relative abundance of specific taxa. The 16S data set was used for metagenome predictions using the software package PICRUSt2. As many as 34 and 40 MetaCyc pathways (from 387 total) were significantly affected by the infection at 5 and 15 dpi, respectively. Notably, C. parvum decreased the abundance of butyrate-producing pathways in bacteria. Low levels of butyrate may increase mucosal inflammation and tissue repair. Our results suggest that the gut inflammation induced by C. parvum infection is associated with the reduction of butyrate-producing bacteria. This insight could be the basis for the development of novel control strategies to improve animal health.

SUBMITTER: Mammeri M

PROVIDER: S-EPMC7596689 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cryptosporidium parvum Infection Depletes Butyrate Producer Bacteria in Goat Kid Microbiome.

Mammeri Mohamed M Obregón Dasiel Alvarez DA Chevillot Aurélie A Polack Bruno B Julien Christine C Pollet Thomas T Cabezas-Cruz Alejandro A Adjou Karim Tarik KT

Frontiers in microbiology 20201016

Cryptosporidium parvum is an important apicomplexan parasite infecting ruminants and humans. We characterized the impact of C. parvum infection on the goat kid microbiome. C. parvum was orally administered to parasite-naïve goats, and infection was monitored for 26 days in fecal samples using immunofluorescence assay and qPCR tests. Age-matched goats served as uninfected controls. A reduction in body weight gain, diarrhea, and dehydration were observed in infected goats comp ...[more]

PMID: 33178145

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Project description:Background: The gut microbiome (GMB) is the first line of defense against enteric pathogens, which are a leading cause of disease and mortality worldwide. One such pathogen, the protozoan Cryptosporidium, causes a variety of digestive disorders that can be devastating and even lethal. The Coquerel's sifaka (Propithecus coquereli) - an endangered, folivorous primate endemic to Madagascar - is precariously susceptible to cryptosporidiosis under captive conditions. If left untreated, infection can rapidly advance to morbidity and death. Objective: To gain a richer understanding of the pathophysiology of this pathogen while also improving captive management of endangered species, we examine the impact of cryptosporidiosis on the GMB of a flagship species known to experience a debilitating disease state upon infection. Design: Using 16S sequencing of DNA extracted from sifaka fecal samples, we compared the microbial communities of healthy sifakas to those of infected individuals, across infection and recovery periods. Results: Over the course of infection, we found that the sifaka GMB responds with decreased microbial diversity and increased community dissimilarity. Compared to the GMB of unaffected individuals, as well as during pre-infection and recovery periods, the GMB during active infection was enriched for microbial taxa associated with dysbiosis and rapid transit time. Time to recovery was inversely related to age, with young animals being slowest to recover GMB diversity and full community membership. Antimicrobial treatment during infection caused a significant depletion in GMB diversity. Conclusions: Although individual sifakas show unique trajectories of microbial loss and recolonization in response to infection, recovering sifakas exhibit remarkably consistent patterns, similar to initial community assembly of the GMB in infants. This observation, in particular, provides biological insight into the rules by which the GMB recovers from the disease state. Fecal transfaunation may prove effective in restoring a healthy GMB in animals with specialized diets.

Project description:Cryptosporidium spp. remain a major cause of waterborne diarrhea and illness in developing countries and represent a significant burden to farmers worldwide. Cryptosporidium parvum virus 1 (CSpV1), of the genus Cryspovirus, was first reported to be present in the cytoplasm of C. parvum in 1997. Full-length genome sequences have been obtained from C. parvum from Iowa (Iowa), Kansas (KSU) and China. We aimed at characterizing the genome of CSpV1 from France and used sequence analysis from Cryptosporidium isolates to explore whether CSpV1 genome diversity varies over time, with geographical sampling location, C. parvum genetic diversity, or ruminant host species. A total of 123 fecal samples of cattle, sheep and goats were collected from 17 different French departments (57 diseased animal fecal samples and 66 healthy animal fecal samples). Subtyping analysis of the C. parvum isolates revealed the presence of two zoonotic subtype families IIa and IId. Sequence analysis of CSpV1 revealed that all CSpV1 from France, regardless of the subtype of C. parvum (IIaA15G2R1, IIaA17G2R1 and IIdA18G1R1) are more closely related to CSpV1 from Turkey, and cluster on a distinct branch from CSpV1 collected from C. parvum subtype IIaA15G2R1 from Asia and North America. We also found that samples collected on a given year or successive years in a given location are more likely to host the same subtype of C. parvum and the same CSpV1 strain. Yet, there is no distinct clustering of CSpV1 per French department or ruminants, probably due to trade, and transmission of C. parvum among host species. Our results point towards (i) a close association between CSpV1 movement and C. parvum movement, (ii) recent migrations of C. parvum among distantly located departments and (iii) incidental transmission of C. parvum between ruminants. All together, these results provide insightful information regarding CSpV1 evolution and suggest the virus might be used as an epidemiological tracer for C. parvum. Future studies need to investigate CSpV1's role in C. parvum virulence and on subtype ability to infect different species.

Project description:BackgroundHundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the Cryptosporidium parvum kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase.ResultsThe C. parvum kinome comprises over 70 members, some of which may be promising drug targets. These C. parvum protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could only be classified as OPK (other protein kinases). In addition, about 25% of the kinases identified did not have any known orthologues outside of Cryptosporidium spp. Comparison of specific kinases with their Plasmodium falciparum and Toxoplasma gondii orthologues revealed some distinct characteristics within the C. parvum kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening CpCDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC₅₀ values of < 10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of CpCDPK1. In addition, structural analysis of CpCDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation.ConclusionsIdentification and comparison of the C. parvum protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.

Project description:BackgroundCryptosporidium parvum is the main cause of calf scour worldwide. With limited therapeutic options and research compared to other Apicomplexa, it is important to understand the parasites' biology and interactions with the host and microbiome in order to develop novel strategies against this infection. The age-dependent nature of symptomatic cryptosporidiosis suggests a link to the undeveloped immune response, the immature intestinal epithelium, and its associated microbiota. This led us to hypothesise that specific features of the early life microbiome could predict calf susceptibility to C. parvum infection.ResultsIn this study, a single faecal swab sample was collected from each calf within the first week of life in a cohort of 346 animals. All 346 calves were subsequently monitored for clinical signs of cryptosporidiosis, and calves that developed diarrhoea were tested for Rotavirus, Coronavirus, E. coli F5 (K99) and C. parvum by lateral flow test (LFT). A retrospective case-control approach was taken whereby a subset of healthy calves (Control group; n = 33) and calves that went on to develop clinical signs of infectious diarrhoea and test positive for C. parvum infection via LFT (Cryptosporidium-positive group; n = 32) were selected from this cohort, five of which were excluded due to low DNA quality. A metagenomic analysis was conducted on the faecal microbiomes of the control group (n = 30) and the Cryptosporidium-positive group (n = 30) prior to infection, to determine features predictive of cryptosporidiosis. Taxonomic analysis showed no significant differences in alpha diversity, beta diversity, and taxa relative abundance between controls and Cryptosporidium-positive groups. Analysis of functional potential showed pathways related to isoprenoid precursor, haem and purine biosynthesis were significantly higher in abundance in calves that later tested positive for C. parvum (q ≤ 0.25). These pathways are either absent or streamlined in the C. parvum parasites. Though the de novo production of isoprenoid precursors, haem and purines are absent, C. parvum has been shown to encode enzymes that catalyse the downstream reactions of these pathway metabolites, indicating that C. parvum may scavenge those products from an external source.ConclusionsThe host has previously been put forward as the source of essential metabolites, but our study suggests that C. parvum may also be able to harness specific metabolic pathways of the microbiota in order to survive and replicate. This finding is important as components of these microbial pathways could be exploited as potential therapeutic targets for the prevention or mitigation of cryptosporidiosis in bovine neonates.

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Cryptosporidium parvum Infection Depletes Butyrate Producer Bacteria in Goat Kid Microbiome.

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<i>Cryptosporidium parvum</i> Infection Depletes Butyrate Producer Bacteria in Goat Kid Microbiome.

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