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William A Petri

Publications and source records attributed to William A Petri.

At least 19 recordsLinked to original sources
PubMed2025

Fecal microbiota transplantation promotes type 2 mucosal immune responses with colonic epithelium proliferation in patients with recurrent Clostridioides difficile.

BACKGROUNDFecal microbiota transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infection (rCDI), yet its mechanism of action remains poorly understood.METHODSWe report the results of a clinical trial of patients undergoing FMT therapy for rCDI (n = 16), which analyzed colon biopsies, plasma, PBMCs, and stool at the time of FMT and 2-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with patients with rCDI. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.RESULTSNo patients experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared with both pre-FMT and healthy control biopsies, inhibiting genes associated with proinflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single-cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.CONCLUSIONWe conclude that FMT promotes proliferation of the colonic epithelium in patients with rCDI, which may drive regeneration and protect against subsequent CDI.TRIAL REGISTRATIONClinicaltrials.gov NCT02797288.FUNDINGThis work was funded by grants from the NIH.

Adult↗
PubMed2006

Evidence for a link between parasite genotype and outcome of infection with Entamoeba histolytica.

The factors determining whether a person infected with Entamoeba histolytica develops disease remain obscure. To investigate whether the parasite genome contributes to the outcome, we have investigated the distribution of parasite genotypes among E. histolytica-infected individuals in Bangladesh. Samples were obtained from individuals who either were asymptomatic, had diarrhea/dysentery, or had developed a liver abscess. Genotypes were determined by using six tRNA-linked polymorphic markers, and their distributions among the three sample groups were evaluated. A significant population differentiation in the genotype distribution was found for four of the six individual markers as well as for the combined genotypes, suggesting that the parasite genome does contribute in some way to the outcome of infection with E. histolytica. The markers themselves do not indicate the nature of the underlying genetic differences, but they may be linked to loci that do have an impact on the outcome of infection.

Animals↗
PubMed2006

Evaluation of Entamoeba histolytica antigen and antibody point-of-care tests for the rapid diagnosis of amebiasis.

The bedside diagnosis of amebiasis could improve patient care. In Bangladesh and Vietnam, a novel and simple-to-use Entamoeba histolytica rapid antigen test had 97% sensitivity and 100% specificity compared to the results of a standard enzyme-linked immunosorbent assay antigen detection method, and a rapid antibody test had 89 to 100% sensitivity and 89 to 95% specificity.

Animals↗
PubMed2006

Entamoeba histolytica encephalitis diagnosed by PCR of cerebrospinal fluid.

Extra-intestinal amebiasis is secondary to invasive intestinal infections and usually results in an amebic liver abscess. Other organs, including lungs, brain, skin, spleen and kidneys, may be involved. Diagnosis of the cerebral infection is of the utmost importance and is most often made by detection of the organism at the time of brain biopsy or at autopsy. We report the first case of Entamoeba histolytica encephalitis diagnosed by PCR of the cerebrospinal fluid. The patient was treated successfully with metronidazole. PCR is an increasingly useful tool for the diagnosis of central nervous system infection and can provide rapid diagnosis.

Adult↗
PubMed2006

Entamoeba histolytica-associated diarrheal illness is negatively associated with the growth of preschool children: evidence from a prospective study.

The enteric protozoa, Cryptosporidium, Giardia and Entamoeba histolytica, cause diarrhea in children. We investigated the association of enteric protozoan-associated diarrheal illness with the nutritional status and growth of preschool children in Dhaka, Bangladesh. The subjects were 221 children aged 2-5 years who were followed prospectively for diarrheal illness for 3 years. The weight and height of the children were measured at entry and at 4-month intervals. Cryptosporidium and E. histolytica were diagnosed with commercially available stool antigen detection kits. Giardia was diagnosed by conventional microscopy. Cryptosporidium- and Giardia-associated diarrheal illness was not associated with the growth of the children. Children with E. histolytica-associated diarrheal illness had lower weight for age Z-score changes (-0.103+/-0.120 vs. 0.176+/-0.052, P=0.038). Similarly, the change in height for age Z-score was lower in children with E. histolytica-associated diarrheal illness (-0.348+/-0.186 vs. 0.142+/-0.08, P=0.018). Children with E. histolytica-associated diarrheal illness were 2.93 times (95% CI 1.01-8.52, P=0.047) more likely to be malnourished and 4.69 times (95% CI 1.55-14.18, P=0.006) more prone to be stunted. Entamoeba histolytica-associated diarrheal illness was negatively associated with the growth of preschool children.

Age Factors↗
PubMed2006

Impact of intestinal colonization and invasion on the Entamoeba histolytica transcriptome.

A genome-wide transcriptional analysis of Entamoeba histolytica was performed on trophozoites isolated from the colon of six infected mice and from in vitro culture. An Affymetrix platform gene expression array was designed for this analysis that included probe sets for 9435 open reading frames (ORFs) and 9066 5' and 3' flanking regions. Transcripts were detected for > 80% of all ORFs. A total of 523 transcripts (5.2% of all E. histolytica genes) were significantly changed in amebae isolated from the intestine on Days 1 and 29 after infection: 326 and 109 solely on Days 1 and 29, and 88 on both days. Quantitative real-time reverse transcriptase PCR confirmed these changes in 11/12 genes tested using mRNA isolated from an additional six mice. Adaptation to the intestinal environment was accompanied by increases in a subset of cell signaling genes including transmembrane kinases, ras and rho family GTPases, and calcium binding proteins. Significant decreases in mRNA abundance for genes involved in glycolysis and concomitant increases in lipases were consistent with a change in energy metabolism. Defense against bacteria present in the intestine (but lacking from in vitro culture) was suggested by alterations in mRNA levels of genes similar to the AIG1 plant antibacterial proteins. Decreases in oxygen detoxification pathways were observed as expected in the anaerobic colonic lumen. Of the known virulence factors the most remarkable changes were a 20-35-fold increase in a cysteine proteinase four-like gene, and a 2-3-fold decrease in two members of the Gal/GalNAc lectin light subunit family. Control of the observed changes in mRNA abundance in the intestine might potentially rest with four related proteins with DNA binding domains that were down-regulated 6-16-fold in the intestinal environment. In conclusion, the first genome-wide analysis of the transcriptome of E. histolytica demonstrated that the vast majority of genes are transcribed in trophozoites, and that in the host intestine trophozoites altered the expression of mRNAs for genes implicated in metabolism, oxygen defense, cell signaling, virulence, antibacterial activity, and DNA binding.

Animals↗
PubMed2006

Diagnosis of amebiasis in Bangladesh.

Diagnosis of amebiasis by microscopic identification of the parasite in stool and liver abscess pus is insensitive and unable to distinguish the invasive parasite E. histolytica from the commensal parasites such as E. dispar and E. moshkovskii. New approaches to the detection of E. histolytica are based on detection of E. histolytica-specific antigen and DNA in stool and other clinical samples. Several molecular diagnostic tests for diagnosis of amebiasis have been developed and used to diagnose E. histolytica in Bangladesh. We have compared the TechLab E. histolytica-specific antigen detection test with PCR assays and with isoenzyme analysis of cultured amebas. The PCR assays are based on amplification of the multi-copy small subunit ribosomal RNA gene of E. histolytica and E. dispar. PCR assays and antigen detection test had comparable sensitivities when performed directly on fresh stool specimens. The correlation of antigen detection with PCR assays for identification of E. histolytica was excellent. TechLab's E. histolytica- specific antigen detection test was both rapid and simple to perform, making it appropriate for use in the developing world, where amebiasis is most prevalent.

Animals↗
PubMed2006

Adherence-blocking vaccine for amebiasis.

The Gal/GalNAc lectin is a candidate vaccine antigen for an amebiasis vaccine due to its mediation of parasite adherence to the human intestine, because partial immunity in humans is associated with a mucosal IgA response against it, and because it is effective as a vaccine against amebic colitis in the murine model. The LecA domain of the Gal/GalNAc lectin contains neutralizing antibody epitopes. LecA contains the active site of the lectin (the carbohydrate recognition domain or "CRD") and has been an effective vaccine antigen in animal models of amebic colitis and liver abscess. Research needs include production of the LecA domain of the Gal/GalNAc lectin by a process that can be transferred to cGMP and optimization for immunogenicity, using adjuvants such as alum, MF59 or QS-21 adjuvants. Accomplishing this will enable testing of the ability of LecA immunizations to protect from amebic colitis in humans.

Animals↗
PubMed2006

Expression and function of a family of transmembrane kinases from the protozoan parasite Entamoeba histolytica.

The signaling proteome of Entamoeba histolytica is made of transmembrane kinases (TMKs) that are rarely found in unicellular eukaryotes. There are 90 TMK genes reported for E. histolytica, and these have been grouped into nine distinct families based on motifs present on both extracellular and kinase domains. Of these, the B1 family was chosen for further analysis. Genomic sequencing revealed the presence of 28 members belonging to this family. Genes corresponding to the majority of these were truncated and not considered for further analysis. Only five members were full length and contained both extracellular and cytosolic kinase domains. BLAST analysis revealed the presence of homologs of these B1 TMKs in the nonpathogenic Entamoeba dispar. However, the ligand binding domains of the orthologous B1 TMKs of the two species showed considerable divergence, indicating the possibility of a correlation with the pathogenic potential of the organism. Only two of the five full-length copies (B1.I.1 and B1.I.2) were expressed in E. histolytica under the culture conditions used. Antisera generated against the extracellular domain of B1.I.1 stained the cell surface, particularly the areas of contact between the trophozoites. Staining was also seen in the frontal and posterior regions of the motile amoeba. An amoebic cell line expressing a truncated version of the B1.I.1 that lacked the kinase domain was generated. Inducible expression of the truncated TMK resulted in a decrease in cellular proliferation and an increase in sensitivity to serum starvation. Our data indicate that the B1.I class of TMKs is involved in parasite proliferation.

Animals↗
PubMed2006

Entamoeba histolytica infection in children and protection from subsequent amebiasis.

The contribution of amebiasis to the burden of diarrheal disease in children and the degree to which immunity is acquired from natural infection were assessed in a 4-year prospective observational study of 289 preschool children in an urban slum in Dhaka, Bangladesh. Entamoeba histolytica infection was detected at least once in 80%, and repeat infection in 53%, of the children who completed 4 years of observation. Annually there were 0.09 episodes/child of E. histolytica-associated diarrhea and 0.03 episodes/child of E. histolytica-associated dysentery. Fecal immunoglobulin A (IgA) anti-parasite Gal/GalNAc lectin carbohydrate recognition domain (anti-CRD) was detected in 91% (183/202) of the children at least once and was associated with a lower incidence of infection and disease. We concluded that amebiasis was a substantial burden on the overall health of the cohort children. Protection from amebiasis was associated with a stool anti-CRD IgA response. The challenge of producing an effective vaccine will be to improve upon naturally acquired immunity, which does not provide absolute protection from reinfection.

Animals↗
PubMed2006

Comparison of a stool antigen detection kit and PCR for diagnosis of Entamoeba histolytica and Entamoeba dispar infections in asymptomatic cyst passers in Iran.

The present study was conducted to compare stool antigen detection with PCR for the diagnosis of Entamoeba sp. infection in asymptomatic cyst passers from Iran. Entamoeba dispar and, in one case, E. moshkovskii were the Entamoeba spp. found in the amebic cyst passers. There was a 100% correlation between the results from the TechLab E. histolytica II stool antigen kit and those from nested PCR. We concluded that E. dispar is much more common in asymptomatic cyst passers in Iran and that antigen detection and PCR are comparable diagnostic modalities.

Animals↗
PubMed2006

Cognitive effects of diarrhea, malnutrition, and Entamoeba histolytica infection on school age children in Dhaka, Bangladesh.

Cognitive function was assessed in 191 Bangladeshi children 6-9 years of age using verbal and nonverbal tests. These scores were added to a health surveillance database that was compiled over the four previous years that includes incidence of diarrhea and Entamoeba histolytica infection and nutritional status. The associations of diarrhea, malnutrition, and social factors with cognitive scores were analyzed statistically, and associations between diarrhea and test scores were controlled for the influence of social factors. Cognitive scores were negatively associated with stunting during school age, as well as the height-for-age and weight-for-age scores at study enrollment. Incidence of diarrhea was associated with nonverbal test scores before, but not after, controlling for socioeconomic factors. Generally E. histolytica infection was not found to independently influence scores, except that E. histolytica-associated dysentery was associated with lower test scores while dysentery of any etiology was not. Thus, malnutrition during the school age years, but not diarrhea or E. histolytica infection, was associated with a lower level of cognitive functioning. This suggested that intervention during school age years may be able to mitigate the cognitive deficiencies associated with malnutrition.

Animals↗
PubMed2005

Kinetics and strain variation of phagosome proteins of Entamoeba histolytica by proteomic analysis.

The protozoan parasite Entamoeba histolytica ingests and feeds on microorganisms and mammalian cells. Phagocytosis is essential for cell growth and implicated in pathogenesis of E. histolytica. We report here the dynamic changes of phagosome proteins during phagosome maturation by proteomic analysis using reversed-phase capillary liquid chromatography and ion trap tandem mass spectrometry. Phagosomes were isolated at various intervals after internalization of latex beads. Immunoblot analysis and electron microscopy verified successful isolation of phagosomes. A total of 159 proteins were identified from the reference strain HM1 at different stages of phagosome maturation. Approximately 70% of them were detected in a time-dependent fashion, suggesting dynamism of phagosome biogenesis. The kinetics of representative proteins were verified by immunoblots and also by video microscopy of live transgenic amebae expressing green fluorescent protein-fused EhRab7A. Furthermore, we observed significant differences in phagosome profiles between HM1 and two recent clinical isolates. Approximately 60% of 229 proteins detected in at least one of these three strains were identified only in one strain, while approximately 20% of these proteins were detected in all three strains. These data should provide significant insights into molecular characterization of phagosome biogenesis, and help to elucidate the pathogenesis of this important infection.

Animals↗
PubMed2005

Roles for the galactose-/N-acetylgalactosamine-binding lectin of Entamoeba in parasite virulence and differentiation.

Entamoeba histolytica, an intestinal protozoan parasite, is a major cause of morbidity and mortality in developing countries. The pathology of the disease is caused by the colonization of the large intestine by the amoebic trophozoites and the invasion of the intestinal epithelium. Some of the trophozoites will eventually differentiate into the infectious cyst form, allowing them to be transmitted out of the bowel and into water supplies to be passed from person to person. Both the virulence of the organism and the differentiation process relies on a galactose-/N-acetylgalactosamine (GalNAc)-binding lectin that is expressed on the surface of trophozoites. The functional activity of this lectin has been shown to be involved in host cell binding, cytotoxicity, complement resistance, induction of encystation, and generation of the cyst wall. The role of the lectin in both differentiation and virulence suggests that it may be a pivotal molecule that determines the severity of the infection from a commensal state resulting from increased encystation to an invasive state. The lectin-glycan interactions that initiate these diverse processes are discussed with emphasis on comparing the binding of host ligands and the interactions involved in encystation.

Acetylgalactosamine↗
PubMed2005

Entamoeba histolytica: the serine-rich gene polymorphism-based genetic variability of clinical isolates from Georgia.

It is generally accepted that a majority of individuals infected by Entamoeba histolytica do not develop symptomatic disease. However, the parasite and the host factors contributing to the development of the disease, remain undetermined. It is also unclear why certain individuals develop extra-intestinal amebiasis without exhibiting apparent intestinal symptoms. An outbreak of amebic liver abscess in Tbilisi, Georgia in 1998-1999 suggested that the causative E. histolytica strain had an unusual propensity for extra-intestinal spread. To correlate the genetic differences with pathogenic potential of the parasite, we have examined the SREHP gene polymorphisms among Georgian E. histolytica isolates. Comparison of polymorphic patterns revealed the presence of several different genotypes of E. histolytica, thus preventing an association of a single genotype with hepatic disease, but supporting the previous finding of extensive genetic diversity among E. histolytica isolates from the same geographic origin.

Animals↗
PubMed2005

Comparison of two methods (microscopy and enzyme-linked immunosorbent assay) for the diagnosis of amebiasis.

Diagnosis of amebiasis is usually performed on a clinical basis alone in most endemic countries having limited economic resources. This epidemiological study was conducted using modern diagnostic tests for amebiasis in the southeastern region of Turkey, an endemic area for amebiasis. The population of this study included patients with symptomatic diarrhea/dysentery attending both Yuzuncu Yil University, Van and Harran University, Sanliurfa, Turkey. A total of 380 stool specimens were collected and examined for Entamoeba by light microscopy (fresh, lugol, and trichrome staining) and stool antigen detection based- enzyme-linked immunosorbent assay (EIA) test (TechLab Entamoeba histolytica II). 24% (91/380) of stool specimens were positive for E. histolytica/Entamoeba dispar trophozoites/cysts microscopically using trichrome staining. 13% (51/380) of the stool specimens were found to be positive for E. histolytica by the EIA test, including 15% (14/91) of microscopy (+) stool specimens and 13% (37/289) of microscopy (-) stool specimens. Enteric parasites were common in these populations with 66% (251/380) of the study population harboring more than one parasite. In addition to the 13% (51/380) of patients determined to have E. histolytica by EIA, eighty-six patients (22.6%) had Blastocystis hominis, 54 (14.2%) Entamoeba coli, 44 (11.5%) Giardia lamblia, 16 (4.2%) Chilomastix mesnili, 15 (3.9%) Iodamoeba bütschlii, 12 (3.1%) Hymenolepis nana, 9 (2.3%) Endolimax nana, 9 (2.3%) Dientamoeba fragilis, and 8 (2.1%) had Ascaris lumbricoides. We concluded that E. histolytica infection was found in 13% of the patients presenting with diarrhea in Van and Sanliurfa Turkey.

Adolescent↗
PubMed2005

The genome of the protist parasite Entamoeba histolytica.

Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.

Animals↗