Tropheryma whippelii

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Martin Altwegg - One of the best experts on this subject based on the ideXlab platform.

  • Tropheryma whippelii DNA in saliva of patients without Whipple's disease.
    Infection, 2000
    Co-Authors: Fabrizio Dutly, Hans Peter Hinrikson, T. Seidel, Silvia Morgenegg, Martin Altwegg, Peter Bauerfeind
    Abstract:

    Tropheryma whippelii is the causative agent of Whipple's disease, a difficult to diagnose systemic illness. Amplification of part of its 16S ribosomal RNA gene(s) has become a standard diagnostic method because of increased sensitivity as compared to classical histopathological analysis. Recently, we demonstrated the presence of T. whippelii DNA by PCR in duodenal biopsies and/or gastric juice of a considerable fraction of individuals without clinical signs of Whipple's disease. In this follow-up study, saliva and dental plaques of the same patients were screened for the presence of T. whippelii DNA. Six out of the 14 previously PCR-positive persons but none of the 17 controls had T. whippelii DNA in their saliva. Our results suggest that Whipple bacteria are ubiquitous environmental or commensal organisms causing Whipple's disease only in a particular subset of individuals, possibly those with an as yet uncharacterized immunological defect.

  • cloning and sequencing of a part of the heat shock protein 65 gene hsp65 of Tropheryma whippelii and its use for detection of t whippelii in clinical specimens by pcr
    Journal of Clinical Microbiology, 2000
    Co-Authors: Silvia Morgenegg, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Using broad-spectrum primers, we have amplified, cloned, and sequenced a 620-bp fragment of the “Tropheryma whippelii” heat shock protein 65 gene (hsp65) from the heart valve of a patient with Whipple's endocarditis. The deduced amino acid sequence shows high similarity to those from actinobacteria, confirming that “T. whippelii” is indeed a member of this phylum. Based on the nucleotide sequence, we have developed a “T. whippelii”-specific seminested PCR. Seventeen patients shown to be positive by 16S ribosomal DNA (rDNA) PCR and/or internal transcribed spacer (ITS) PCR were also positive by hsp65 PCR. All 33 control specimens from patients without Whipple's disease and negative for “T. whippelii” by both seminested 16S rDNA and ITS PCR remained negative. All amplicons digested with XhoI revealed an identical restriction pattern. Eight of the 17 hsp65 amplicons representing all three previously described ITS types were sequenced. Three of the amplicons showed slight differences, but none of the mutations detected affected the amino acid sequence of the corresponding protein. We conclude that the hsp65 gene is a suitable target for the specific detection of “T. whippelii.” Its product represents a putative antigen for a future serodiagnostic assay.

  • Analysis of the actinobacterial insertion in domain III of the 23S rRNA gene of uncultured variants of the bacterium associated with Whipple's disease using broad-range and 'Tropheryma whippelii'-specific PCR
    International Journal of Systematic and Evolutionary Microbiology, 2000
    Co-Authors: Hans Peter Hinrikson, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Heterogeneity in the 16S-23S rDNA spacer of uncultured 'Tropheryma whippelii' has previously been reported. In this study, the hypervariable insertion in the 23S rDNA domain III characteristic for actinobacteria was analysed. The finding of a unique sequence virtually identical among the subtypes supports the classification of 'T. whippelii' among the actinobacteria and the concept of three subtypes rather than three subspecies, and provides an alternative target for diagnostic assays.

  • evaluation of a specific nested pcr targeting domain iii of the 23s rrna gene of Tropheryma whippelii and proposal of a classification system for its molecular variants
    Journal of Clinical Microbiology, 2000
    Co-Authors: Hans Peter Hinrikson, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Tropheryma whippelii”-associated infections are usually confirmed histopathologically by using light microscopy. PCR assays targeting the 16S rRNA gene (16S rDNA) of “T. whippelii” are increasingly being applied for this purpose. Compared to microscopic analysis, PCR seems to be more sensitive, as indicated by the fact that several cases of Whipple's disease with negative histopathological findings but positive PCR results have been reported. Considering the lack of pathognomonic clinical features for this disease and the fact that “T. whippelii” DNA has repeatedly been found in patients without clinical Whipple's disease, such PCR results should be confirmed by additional tests. We have, therefore, evaluated a “T. whippelii”-specific nested PCR targeting domain III of the 23S rDNA with 41 clinical specimens known to contain “T. whippelii” 16S rDNA. All of these specimens were also positive for “T. whippelii” 23S rDNA. The specificity of the test was shown by sequencing of the amplicons and by the absence of amplicons in 38 negative controls. We consider this PCR test to be a suitable tool for confirming the presence of “T. whippelii” DNA in specimens with inconclusive histopathological findings. The information derived from sequencing of the partial “T. whippelii” 23S rDNA was then combined with our recent data of the 16S-23S rDNA spacer region of this organism. Overall, four different rDNA types are recognized in our proposed classification system for molecular variants of “T. whippelii.” This preliminary scheme may provide a basis for further epidemiological and clinical studies with “T. whippelii” and associated diseases.

  • Cloning and Sequencing of a Part of the Heat Shock Protein 65 Gene (hsp65) of “Tropheryma whippelii” and Its Use for Detection of “T. whippelii” in Clinical Specimens by PCR
    Journal of clinical microbiology, 2000
    Co-Authors: Silvia Morgenegg, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Using broad-spectrum primers, we have amplified, cloned, and sequenced a 620-bp fragment of the “Tropheryma whippelii” heat shock protein 65 gene (hsp65) from the heart valve of a patient with Whipple's endocarditis. The deduced amino acid sequence shows high similarity to those from actinobacteria, confirming that “T. whippelii” is indeed a member of this phylum. Based on the nucleotide sequence, we have developed a “T. whippelii”-specific seminested PCR. Seventeen patients shown to be positive by 16S ribosomal DNA (rDNA) PCR and/or internal transcribed spacer (ITS) PCR were also positive by hsp65 PCR. All 33 control specimens from patients without Whipple's disease and negative for “T. whippelii” by both seminested 16S rDNA and ITS PCR remained negative. All amplicons digested with XhoI revealed an identical restriction pattern. Eight of the 17 hsp65 amplicons representing all three previously described ITS types were sequenced. Three of the amplicons showed slight differences, but none of the mutations detected affected the amino acid sequence of the corresponding protein. We conclude that the hsp65 gene is a suitable target for the specific detection of “T. whippelii.” Its product represents a putative antigen for a future serodiagnostic assay.

David A. Relman - One of the best experts on this subject based on the ideXlab platform.

  • Editorial: The Whipple Bacillus Lives (Ex Vivo)!
    2016
    Co-Authors: David A. Relman, Departments Microbiology, S. Immunology, Of Medicine
    Abstract:

    Cultivation of the bacillus associated with Whipple's disease, Tropheryma whippelii, has been an elusive goal for many gen-erations of clinicians and microbiologists familiar with this disease. The desire to identify this enigmatic organism has motivated many of these efforts. Many purported successes have later proven erroneous, and many more unsuccessful at-tempts have never been reported [1]. Cell-free media, animal cells, and animals themselves have all been used, resulting in recovery of a wide range of bacterial species, including mem-bers of the Corynebacterium, Streptococcus, Propionibacte-rium, and Haemophilus genera. The rough resemblance ofRho-dococcus equi-, Mycobacterium paratuberculosis-, and Mycobacterium avium complex-associated diseases in foals, cows, and humans, respectively, to Whipple's disease has been noted; however, pathology closely mimicking that of the latte

  • Localization of Tropheryma whippelii rRNA in Tissues from Patients with Whipple's Disease
    The Journal of infectious diseases, 2001
    Co-Authors: David N. Fredricks, David A. Relman
    Abstract:

    Whipple's disease is caused by a cultivation-resistant bacterium, Tropheryma whippelii. Ultrastructural studies of intestinal biopsy specimens from patients with Whipple's disease have shown that intracellular and extracellular bacteria are present, but the preferred site of growth is unknown. Tissue sections from 8 patients with Whipple's disease and from 19 healthy control subjects were analyzed by use of fluorescence in situ hybridization and laser scanning confocal microscopy, to determine the location of rRNA that would indicate the presence of metabolically active bacteria. T. whippelii rRNA was most prevalent near the tips of intestinal villi, in the lamina propria, just basal to epithelial cells. Most of the bacterial rRNA signal appeared to be located between cells and did not colocalize with the human intracellular protein vimentin. The location of bacterial rRNA in tissues from patients with Whipple's disease provides evidence that bacteria are growing outside cells and suggests that T. whippelii is not an obligate intracellular pathogen.

  • Whipple's Disease and Tropheryma whippelii: Secrets Slowly Revealed
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2001
    Co-Authors: Matthias Maiwald, David A. Relman
    Abstract:

    Whipple's disease was described in 1907 and was designated "intestinal lipodystrophy," despite the detection of bacteria in 1 specimen. This finding was later substantiated by the success of antibiotic therapy, which resulted in dramatic clinical responses, and by use of electron microscopy, which detected monomorphic bacilli in affected tissues. Many attempts at culture failed, and these bacteria were characterized as actinomycetes for the first time by means of broad-range 16S rDNA amplification and molecular phylogenetic methods. The name "Tropheryma whippelii" was proposed for this bacterium. Whipple's disease is a systemic disease that affects many organ systems, producing protean manifestations. This article summarizes recent developments with regard to this topic as well as unanswered questions regarding the pathogenesis and acquisition of infection, the biology and ecology of the organism, the clinical spectrum of disease, diagnosis of the disease, and therapy.

  • Tropheryma whippelii dna is rare in the intestinal mucosa of patients without other evidence of whipple disease
    Annals of Internal Medicine, 2001
    Co-Authors: Matthias Maiwald, Axel Von Herbay, Manal F. Abdelmalek, David H. Persing, David N. Fredricks, Shawn P Mitchell, Jill N Thorvilson, David A. Relman
    Abstract:

    Background: Little is known about the pathogenesis of Whipple disease, the reservoirs of Tropheryma whippelii, and the proportion of persons harboring the bacterium without classic intestinal abnormalities. Objective: To assess the presence of T. whippelii in patients undergoing upper endoscopy for a variety of indications. Design: Prospective and routine diagnostic examination of patients. Setting: Three academic medical centers in California; Minnesota; and Heidelberg, Germany. Patients: 342 patients undergoing endoscopy for evaluation of dyspepsia or possible peptic ulcer (group A, 173 patients), malabsorption (group B, 37 patients), or clinical suspicion of Whipple disease (group C, 132 patients). Measurements: Small-intestinal biopsy specimens were tested by polymerase chain reaction for T. whippelii DNA and examined for histopathologic abnormalities. Results: All patients with negative histologic findings also had negative results for T. whippelii DNA. Conclusions: T. whippelii occurs only rarely in intestinal mucosa that lacks histopathologic evidence of Whipple disease. The human small intestinal mucosa is an unlikely reservoir for this organism.

  • Organization, structure, and variability of the rRNA operon of the Whipple's disease bacterium (Tropheryma whippelii).
    Journal of bacteriology, 2000
    Co-Authors: Matthias Maiwald, Axel Von Herbay, Paul W. Lepp, David A. Relman
    Abstract:

    Whipple's disease is a systemic disorder associated with a cultivation-resistant, poorly characterized actinomycete, Tropheryma whippelii. We determined a nearly complete rRNA operon sequence of T. whippelii from specimens from 3 patients with Whipple's disease, as well as partial operon sequences from 43 patients. Variability was observed in the 16S-23S rRNA spacer sequences, leading to the description of five distinct sequence types. One specimen contained two spacer sequence types, raising the possibility of a double infection. Secondary structure models for the primary rRNA transcript and mature rRNAs revealed rare or unique features.

Fabrizio Dutly - One of the best experts on this subject based on the ideXlab platform.

  • Whipple's Disease and “Tropheryma whippelii
    Clinical microbiology reviews, 2001
    Co-Authors: Fabrizio Dutly
    Abstract:

    Whipple's disease is a rare bacterial infection that may involve any organ system in the body. It occurs primarily in Caucasian males older than 40 years. The gastrointestinal tract is the most frequently involved organ, with manifestations such as abdominal pain, malabsorption syndrome with diarrhea, and weight loss. Other signs include low-grade fever, lymphadenopathy, skin hyperpigmentation, endocarditis, pleuritis, seronegative arthritis, uveitis, spondylodiscitis, and neurological manifestations, and these signs may occur in the absence of gastrointestinal manifestations. Due to the wide variability of manifestations, clinical diagnosis is very difficult and is often made only years or even decades after the initial symptoms have appeared. Trimethoprim-sulfamethoxazole for at least 1 year is usually considered adequate to eradicate the infection. The microbiological diagnosis of this insidious disease is rendered difficult by the virtual lack of culture and serodiagnostic methods. It is usually based on the demonstration of periodic acid-Schiff-positive particles in infected tissues and/or the presence of bacteria with an unusual trilaminar cell wall ultrastructure by electron microscopy. Recently, the Whipple bacteria have been characterized at the molecular level by amplification of their 16S rRNA gene(s). Phylogenetic analysis of these sequences revealed a new bacterial species related to the actinomycete branch which was named “Tropheryma whippelli.” Based on its unique 16S ribosomal DNA (rDNA) sequence, species-specific primers were selected for the detection of the organism in clinical specimens by PCR. This technique is currently used as one of the standard methods for establishing the diagnosis of Whipple's disease. Specific and broad-spectrum PCR amplifications mainly but not exclusively from extraintestinal specimens have significantly improved diagnosis, being more sensitive than histopathologic analysis. However, “T. whippelii” DNA has also been found in persons without clinical and histological evidence of Whipple's disease. It is unclear whether these patients are true asymptomatic carriers or whether differences in virulence exist among strains of “T. whippelii” that might account for the variable clinical manifestations. So far, six different “T. whippelii” subtypes have been found by analysis of their 16S-23S rDNA spacer region. Further studies of the pathogen “T. whippelii” as well as the host immune response are needed to fully understand this fascinating disease. The recent cultivation of the organisms is a promising major step in this direction.

  • Tropheryma whippelii DNA in saliva of patients without Whipple's disease.
    Infection, 2000
    Co-Authors: Fabrizio Dutly, Hans Peter Hinrikson, T. Seidel, Silvia Morgenegg, Martin Altwegg, Peter Bauerfeind
    Abstract:

    Tropheryma whippelii is the causative agent of Whipple's disease, a difficult to diagnose systemic illness. Amplification of part of its 16S ribosomal RNA gene(s) has become a standard diagnostic method because of increased sensitivity as compared to classical histopathological analysis. Recently, we demonstrated the presence of T. whippelii DNA by PCR in duodenal biopsies and/or gastric juice of a considerable fraction of individuals without clinical signs of Whipple's disease. In this follow-up study, saliva and dental plaques of the same patients were screened for the presence of T. whippelii DNA. Six out of the 14 previously PCR-positive persons but none of the 17 controls had T. whippelii DNA in their saliva. Our results suggest that Whipple bacteria are ubiquitous environmental or commensal organisms causing Whipple's disease only in a particular subset of individuals, possibly those with an as yet uncharacterized immunological defect.

  • cloning and sequencing of a part of the heat shock protein 65 gene hsp65 of Tropheryma whippelii and its use for detection of t whippelii in clinical specimens by pcr
    Journal of Clinical Microbiology, 2000
    Co-Authors: Silvia Morgenegg, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Using broad-spectrum primers, we have amplified, cloned, and sequenced a 620-bp fragment of the “Tropheryma whippelii” heat shock protein 65 gene (hsp65) from the heart valve of a patient with Whipple's endocarditis. The deduced amino acid sequence shows high similarity to those from actinobacteria, confirming that “T. whippelii” is indeed a member of this phylum. Based on the nucleotide sequence, we have developed a “T. whippelii”-specific seminested PCR. Seventeen patients shown to be positive by 16S ribosomal DNA (rDNA) PCR and/or internal transcribed spacer (ITS) PCR were also positive by hsp65 PCR. All 33 control specimens from patients without Whipple's disease and negative for “T. whippelii” by both seminested 16S rDNA and ITS PCR remained negative. All amplicons digested with XhoI revealed an identical restriction pattern. Eight of the 17 hsp65 amplicons representing all three previously described ITS types were sequenced. Three of the amplicons showed slight differences, but none of the mutations detected affected the amino acid sequence of the corresponding protein. We conclude that the hsp65 gene is a suitable target for the specific detection of “T. whippelii.” Its product represents a putative antigen for a future serodiagnostic assay.

  • Analysis of the actinobacterial insertion in domain III of the 23S rRNA gene of uncultured variants of the bacterium associated with Whipple's disease using broad-range and 'Tropheryma whippelii'-specific PCR
    International Journal of Systematic and Evolutionary Microbiology, 2000
    Co-Authors: Hans Peter Hinrikson, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Heterogeneity in the 16S-23S rDNA spacer of uncultured 'Tropheryma whippelii' has previously been reported. In this study, the hypervariable insertion in the 23S rDNA domain III characteristic for actinobacteria was analysed. The finding of a unique sequence virtually identical among the subtypes supports the classification of 'T. whippelii' among the actinobacteria and the concept of three subtypes rather than three subspecies, and provides an alternative target for diagnostic assays.

  • evaluation of a specific nested pcr targeting domain iii of the 23s rrna gene of Tropheryma whippelii and proposal of a classification system for its molecular variants
    Journal of Clinical Microbiology, 2000
    Co-Authors: Hans Peter Hinrikson, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Tropheryma whippelii”-associated infections are usually confirmed histopathologically by using light microscopy. PCR assays targeting the 16S rRNA gene (16S rDNA) of “T. whippelii” are increasingly being applied for this purpose. Compared to microscopic analysis, PCR seems to be more sensitive, as indicated by the fact that several cases of Whipple's disease with negative histopathological findings but positive PCR results have been reported. Considering the lack of pathognomonic clinical features for this disease and the fact that “T. whippelii” DNA has repeatedly been found in patients without clinical Whipple's disease, such PCR results should be confirmed by additional tests. We have, therefore, evaluated a “T. whippelii”-specific nested PCR targeting domain III of the 23S rDNA with 41 clinical specimens known to contain “T. whippelii” 16S rDNA. All of these specimens were also positive for “T. whippelii” 23S rDNA. The specificity of the test was shown by sequencing of the amplicons and by the absence of amplicons in 38 negative controls. We consider this PCR test to be a suitable tool for confirming the presence of “T. whippelii” DNA in specimens with inconclusive histopathological findings. The information derived from sequencing of the partial “T. whippelii” 23S rDNA was then combined with our recent data of the 16S-23S rDNA spacer region of this organism. Overall, four different rDNA types are recognized in our proposed classification system for molecular variants of “T. whippelii.” This preliminary scheme may provide a basis for further epidemiological and clinical studies with “T. whippelii” and associated diseases.

Hans Peter Hinrikson - One of the best experts on this subject based on the ideXlab platform.

  • Tropheryma whippelii DNA in saliva of patients without Whipple's disease.
    Infection, 2000
    Co-Authors: Fabrizio Dutly, Hans Peter Hinrikson, T. Seidel, Silvia Morgenegg, Martin Altwegg, Peter Bauerfeind
    Abstract:

    Tropheryma whippelii is the causative agent of Whipple's disease, a difficult to diagnose systemic illness. Amplification of part of its 16S ribosomal RNA gene(s) has become a standard diagnostic method because of increased sensitivity as compared to classical histopathological analysis. Recently, we demonstrated the presence of T. whippelii DNA by PCR in duodenal biopsies and/or gastric juice of a considerable fraction of individuals without clinical signs of Whipple's disease. In this follow-up study, saliva and dental plaques of the same patients were screened for the presence of T. whippelii DNA. Six out of the 14 previously PCR-positive persons but none of the 17 controls had T. whippelii DNA in their saliva. Our results suggest that Whipple bacteria are ubiquitous environmental or commensal organisms causing Whipple's disease only in a particular subset of individuals, possibly those with an as yet uncharacterized immunological defect.

  • Analysis of the actinobacterial insertion in domain III of the 23S rRNA gene of uncultured variants of the bacterium associated with Whipple's disease using broad-range and 'Tropheryma whippelii'-specific PCR
    International Journal of Systematic and Evolutionary Microbiology, 2000
    Co-Authors: Hans Peter Hinrikson, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Heterogeneity in the 16S-23S rDNA spacer of uncultured 'Tropheryma whippelii' has previously been reported. In this study, the hypervariable insertion in the 23S rDNA domain III characteristic for actinobacteria was analysed. The finding of a unique sequence virtually identical among the subtypes supports the classification of 'T. whippelii' among the actinobacteria and the concept of three subtypes rather than three subspecies, and provides an alternative target for diagnostic assays.

  • evaluation of a specific nested pcr targeting domain iii of the 23s rrna gene of Tropheryma whippelii and proposal of a classification system for its molecular variants
    Journal of Clinical Microbiology, 2000
    Co-Authors: Hans Peter Hinrikson, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Tropheryma whippelii”-associated infections are usually confirmed histopathologically by using light microscopy. PCR assays targeting the 16S rRNA gene (16S rDNA) of “T. whippelii” are increasingly being applied for this purpose. Compared to microscopic analysis, PCR seems to be more sensitive, as indicated by the fact that several cases of Whipple's disease with negative histopathological findings but positive PCR results have been reported. Considering the lack of pathognomonic clinical features for this disease and the fact that “T. whippelii” DNA has repeatedly been found in patients without clinical Whipple's disease, such PCR results should be confirmed by additional tests. We have, therefore, evaluated a “T. whippelii”-specific nested PCR targeting domain III of the 23S rDNA with 41 clinical specimens known to contain “T. whippelii” 16S rDNA. All of these specimens were also positive for “T. whippelii” 23S rDNA. The specificity of the test was shown by sequencing of the amplicons and by the absence of amplicons in 38 negative controls. We consider this PCR test to be a suitable tool for confirming the presence of “T. whippelii” DNA in specimens with inconclusive histopathological findings. The information derived from sequencing of the partial “T. whippelii” 23S rDNA was then combined with our recent data of the 16S-23S rDNA spacer region of this organism. Overall, four different rDNA types are recognized in our proposed classification system for molecular variants of “T. whippelii.” This preliminary scheme may provide a basis for further epidemiological and clinical studies with “T. whippelii” and associated diseases.

  • Evaluation of a Specific Nested PCR Targeting Domain III of the 23S rRNA Gene of “Tropheryma whippelii” and Proposal of a Classification System for Its Molecular Variants
    Journal of clinical microbiology, 2000
    Co-Authors: Hans Peter Hinrikson, Fabrizio Dutly, Martin Altwegg
    Abstract:

    Tropheryma whippelii”-associated infections are usually confirmed histopathologically by using light microscopy. PCR assays targeting the 16S rRNA gene (16S rDNA) of “T. whippelii” are increasingly being applied for this purpose. Compared to microscopic analysis, PCR seems to be more sensitive, as indicated by the fact that several cases of Whipple's disease with negative histopathological findings but positive PCR results have been reported. Considering the lack of pathognomonic clinical features for this disease and the fact that “T. whippelii” DNA has repeatedly been found in patients without clinical Whipple's disease, such PCR results should be confirmed by additional tests. We have, therefore, evaluated a “T. whippelii”-specific nested PCR targeting domain III of the 23S rDNA with 41 clinical specimens known to contain “T. whippelii” 16S rDNA. All of these specimens were also positive for “T. whippelii” 23S rDNA. The specificity of the test was shown by sequencing of the amplicons and by the absence of amplicons in 38 negative controls. We consider this PCR test to be a suitable tool for confirming the presence of “T. whippelii” DNA in specimens with inconclusive histopathological findings. The information derived from sequencing of the partial “T. whippelii” 23S rDNA was then combined with our recent data of the 16S-23S rDNA spacer region of this organism. Overall, four different rDNA types are recognized in our proposed classification system for molecular variants of “T. whippelii.” This preliminary scheme may provide a basis for further epidemiological and clinical studies with “T. whippelii” and associated diseases.

  • detection of three different types of Tropheryma whippelii directly from clinical specimens by sequencing single strand conformation polymorphism sscp analysis and type specific pcr of their 16s 23s ribosomal intergenic spacer region
    International Journal of Systematic and Evolutionary Microbiology, 1999
    Co-Authors: Hans Peter Hinrikson, Fabrizio Dutly, Satheesh Nair, Martin Altwegg
    Abstract:

    The 16S-23S rDNA intergenic spacer region of organisms identical with or closely related to 'Tropheryma whippelii', the uncultivated causative agent of Whipple's disease, was analysed directly from 38 clinical specimens of 28 patients using a specific nested PCR followed by direct sequencing. As compared to the reference sequence in public databases, two novel 'T. whippelii' spacer types were recognized. In the absence of DNA-DNA hybridization data it is uncertain whether the three types found represent subtypes of a single species or three different but closely related species. Methods were developed to detect all three variants by single-strand conformation polymorphism analysis and by type-specific PCR assays, thus allowing the screening of large numbers of specimens. Further studies may provide a clue to the possible associations between the type of infecting strain and the various clinical presentations of Whipple's disease.

Matthias Maiwald - One of the best experts on this subject based on the ideXlab platform.

  • Whipple's Disease and Tropheryma whippelii: Secrets Slowly Revealed
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2001
    Co-Authors: Matthias Maiwald, David A. Relman
    Abstract:

    Whipple's disease was described in 1907 and was designated "intestinal lipodystrophy," despite the detection of bacteria in 1 specimen. This finding was later substantiated by the success of antibiotic therapy, which resulted in dramatic clinical responses, and by use of electron microscopy, which detected monomorphic bacilli in affected tissues. Many attempts at culture failed, and these bacteria were characterized as actinomycetes for the first time by means of broad-range 16S rDNA amplification and molecular phylogenetic methods. The name "Tropheryma whippelii" was proposed for this bacterium. Whipple's disease is a systemic disease that affects many organ systems, producing protean manifestations. This article summarizes recent developments with regard to this topic as well as unanswered questions regarding the pathogenesis and acquisition of infection, the biology and ecology of the organism, the clinical spectrum of disease, diagnosis of the disease, and therapy.

  • Tropheryma whippelii dna is rare in the intestinal mucosa of patients without other evidence of whipple disease
    Annals of Internal Medicine, 2001
    Co-Authors: Matthias Maiwald, Axel Von Herbay, Manal F. Abdelmalek, David H. Persing, David N. Fredricks, Shawn P Mitchell, Jill N Thorvilson, David A. Relman
    Abstract:

    Background: Little is known about the pathogenesis of Whipple disease, the reservoirs of Tropheryma whippelii, and the proportion of persons harboring the bacterium without classic intestinal abnormalities. Objective: To assess the presence of T. whippelii in patients undergoing upper endoscopy for a variety of indications. Design: Prospective and routine diagnostic examination of patients. Setting: Three academic medical centers in California; Minnesota; and Heidelberg, Germany. Patients: 342 patients undergoing endoscopy for evaluation of dyspepsia or possible peptic ulcer (group A, 173 patients), malabsorption (group B, 37 patients), or clinical suspicion of Whipple disease (group C, 132 patients). Measurements: Small-intestinal biopsy specimens were tested by polymerase chain reaction for T. whippelii DNA and examined for histopathologic abnormalities. Results: All patients with negative histologic findings also had negative results for T. whippelii DNA. Conclusions: T. whippelii occurs only rarely in intestinal mucosa that lacks histopathologic evidence of Whipple disease. The human small intestinal mucosa is an unlikely reservoir for this organism.

  • Organization, structure, and variability of the rRNA operon of the Whipple's disease bacterium (Tropheryma whippelii).
    Journal of bacteriology, 2000
    Co-Authors: Matthias Maiwald, Axel Von Herbay, Paul W. Lepp, David A. Relman
    Abstract:

    Whipple's disease is a systemic disorder associated with a cultivation-resistant, poorly characterized actinomycete, Tropheryma whippelii. We determined a nearly complete rRNA operon sequence of T. whippelii from specimens from 3 patients with Whipple's disease, as well as partial operon sequences from 43 patients. Variability was observed in the 16S-23S rRNA spacer sequences, leading to the description of five distinct sequence types. One specimen contained two spacer sequence types, raising the possibility of a double infection. Secondary structure models for the primary rRNA transcript and mature rRNAs revealed rare or unique features.

  • Organization, structure, and variability of the rRNA operon of the Whipple’s disease bacterium (Tropheryma whippelii
    2000
    Co-Authors: Matthias Maiwald, Axel Von Herbay, Paul W. Lepp, David A. Relman
    Abstract:

    Whipple’s disease is a systemic disorder associated with a cultivation-resistant, poorly characterized acti-nomycete, Tropheryma whippelii. We determined a nearly complete rRNA operon sequence of T. whippelii from specimens from 3 patients with Whipple’s disease, as well as partial operon sequences from 43 patients. Variability was observed in the 16S-23S rRNA spacer sequences, leading to the description of five distinct sequence types. One specimen contained two spacer sequence types, raising the possibility of a double infec-tion. Secondary structure models for the primary rRNA transcript and mature rRNAs revealed rare or unique features. Whipple’s disease was described in 1907 (as intestinal lipo-dystrophy) and is a multisystem disorder of humans involving the intestinal tract as well as various other organs (3). A con-stant feature of the disease is the presence in affected tissues of uniform bacteria that are approximately 0.2 by 1.5 to 2.5 mm. These bacteria have a characteristic morphology when viewed with electron microscopy (25). However, numerous attempts to cultivate this bacterium have failed (3). In 1997, propagation i

  • Environmental occurrence of the Whipple's disease bacterium (Tropheryma whippelii).
    Applied and environmental microbiology, 1998
    Co-Authors: Matthias Maiwald, Frank Schuhmacher, Hans-jürgen Ditton, Axel Von Herbay
    Abstract:

    Whipple’s disease is a systemic disorder in which a gram-positive rod-shaped bacterium is constantly present in infected tissues. After numerous unsuccessful attempts to culture this bacterium, it was eventually characterized by 16S rRNA gene analysis to be a member of the actinomycetes. The name Tropheryma whippelii was proposed. Until now, the bacterium has only been found in infected human tissues, but there is no evidence for human-to-human transmission. Here we report the detection of DNA specific for the Whipple’s disease bacterium in 25 of 38 wastewater samples from five different sewage treatment plants in the area of Heidelberg, Germany. These findings provide the first evidence that T. whippelii occurs in the environment, within a polymicrobial community. This is in accordance with the phylogenetic relationship of this bacterium as well as with known epidemiological aspects of Whipple’s disease. Our data argue for an environmental source for infection with the Whipple’s disease bacterium.