Publications (12)37.72 Total impact
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Article: Fungal encephalitis in human autopsy cases is associated with extensive neuronal damage but only minimal repair.
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ABSTRACT: AIMS: The present study aimed at examining neuronal injury and repair in post mortem brain sections of humans who died from fungal CNS infections. METHODS: Histological and immunohistochemical abnormalities in 15 autopsy cases with fungal CNS infections from 1990 to 2008 were compared to findings in 10 age- und sex-matched control cases that died from acute non-neurological causes. The fungal pathogens were identified by culture or PCR and morphology in post mortem tissue. Seven patients with fungal encephalitis had either an organ transplantation or a malignant haematological disorder; 5 out of 15 did not have a classical pre-disposing illness but suffered from severe septic infections as the principal cause of immunosuppression, and 3 from alcoholism. RESULTS: Fungal organisms detected were Aspergillus spp. and other moulds, Candida spp. and black yeast-like fungi including Cladosporium spp.. Histological analyses identified microglial activation, astrocytosis and axonal injury in the white matter without additional demyelination as characteristic features of this infectious disease. An increased rate of hippocampal neuronal apoptosis was detected in fungal encephalitis, while the number of recently generated TUC-4 and calretinin-expressing neurons in the dentate gyrus did not differ between patients and controls. CONCLUSIONS: Unlike in other infectious diseases of the nervous system where a co-existence of damage and repair was observed, fungal encephalitis is characterized by strong damage and minimal neuronal regeneration.Neuropathology and Applied Neurobiology 03/2013; · 3.80 Impact Factor -
Article: Epidemiological association of Campylobacter jejuni groups with pathogenicity-associated genetic markers.
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ABSTRACT: BACKGROUND: Campylobacter jejuni, the most leading cause for bacterial gastroenteritis worldwide, shows a high genetic diversity among its isolates. Recently, we demonstrated the existence of six C. jejuni-groups by combining MLST with six genetic markers. These groups were further characterized by the detection of cj1321-cj1326, fucP, cj0178, cj0755/cfrA, ceuE, pldA, cstII, and cstIII in order (I.) to show further associations between these different genetic markers and MLST CCs. Moreover, different studies were able to associate several of these markers: a sialylated lipoologosaccharide (cstII/III+), the gamma-glytamyl-transpeptidase (ggt+), and the absence of a certain allele of the enterochelin-uptake-binding-protein (ceuE11168-) with severe campylobacteriosis, bloody diarrhea and unpleasant outcome. Additionally more than half of human Campylobacter-isolates were assigned to a non-livestock clade associated with the absence of cj1321-cj1326. These isolates were considered as mere colonizers. From the combination of marker genes, the ratio of human isolates in a specific group, and clinical data (II.) it should be demonstrated to which of the previous defined groups these Campylobacter-subpopulations, associated with higher virulence, correspond. RESULTS: Besides the marker gene pldA, all new estimated genetic markers show significant differences in their distribution among the various MLST-based groups. Especially the genes for cj1321-cj1326, fucP, cj0178, cj0755/cfrA are widely associated with each other and split the study population into two major and seven intermediate groups substantiating the previous group-definition, whereas cstII and cstIII indicate at least three groups following an independent distribution pattern. CONCLUSIONS: Based on these data a group of C. jejuni-isolates characterized by the presence of ansB, dmsA, ggt, and the absence of cj1365c, cj1585c, cj1321-cj1326, fucP, cj0178, cj0755/cfrA, and cstII/III was associated with a higher prevalence in human campylobacteriosis, bloody diarrhea as well as hospitalization and bears obviously a higher virulence for humans. In contrast to that better livestock-adapted groups characterized by the ability to utilize L-fucose and the presence of all of the ve identied putative C. jejuni iron-uptake systems as well as cj1321-cj1326, cj1365c, cj1585c, and cstII and/or cstIII (sialylated lipoologosaccharide) is more prevalent in animal hosts and was secondary associated with less severe campylobacteriosis.BMC Microbiology 08/2012; 12(1):171. · 3.04 Impact Factor -
Article: Interlaboratory comparison of PCR-based identification of Candida and Aspergillus DNA in spiked blood samples.
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ABSTRACT: Despite PCR per se being a powerful and sensitive technique, regarding the detection of fungi in patients' blood, no consensus for a standardised PCR protocol yet exists. To complement other ongoing or accomplished studies which tackle this problem, the German Reference Center for Systemic Mycoses conducted an interlaboratory comparison starting with blood samples spiked with fungal cell elements. Altogether, six laboratories using in-house PCR-protocols from Germany and Austria participated in the trial. Blood samples were spiked with vital cells of Candida albicans or Aspergillus fumigatus. Candida was used in the yeast form, whereas Aspergillus cells were either spiked as conidia or as very young germlings, also known as smoo cells. Spiked blood samples contained between 10 and 10 000 cells ml(-1). Depending on the techniques used for fungal cell disruption and DNA-amplification, detection quality was variable between laboratories, but also differed within single laboratories in different trials particularly for samples spiked with less than 100 cells ml(-1). Altogether, at least regarding the detection of A. fumigatus, two of six laboratories showed constant reliable test results also with low fungal cell number spiked samples. Protocols used by these labs do not differ substantially from others. However, as particularities, one protocol included a conventional phenol chloroform extraction during the DNA preparation process and the other included a real time PCR-protocol based on FRET probes. Other laboratory comparisons on the basis of clinical samples should follow to further evaluate the procedures. The difficulties and problems of such trials in general are discussed.Mycoses 01/2012; 55(5):426-34. · 2.25 Impact Factor -
Article: Sulphite : cytochrome c oxidoreductase deficiency in Campylobacter jejuni reduces motility, host cell adherence and invasion.
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ABSTRACT: Campylobacter jejuni lacks the enzyme phosphofructokinase and, consequently, is incapable of metabolizing glucose. Instead, the pathogen uses a number of other chemicals to serve as electron donors. Like chemolithotrophic bacteria, C. jejuni is able to respire sulphite in the presence of a sulphite : cytochrome c oxidoreductase (SOR) that is encoded by the genes cj0004c and cj0005c; the former encodes a monohaem cytochrome c oxidoreductase and the latter a molybdopterin oxidoreductase. After screening of a transposon-based mutant library, we identified a mutant with an insertion in gene cj0005c that was strongly reduced in its capacity to infect Caco2 cells. Further characterization of a corresponding non-random knockout mutant together with a complemented mutant and the parental strain showed the cj0005c-deficient mutant to exhibit clearly reduced motility and diminished adherence to host cells. Furthermore, the transcription of genes responsible for the synthesis of, in particular, legionaminic acid was downregulated and the mutant had a reduced capacity to autoagglutinate. In contrast, neither the proliferation of the mutant, nor its intracellular ATP content, was altered compared to the parental strain.Microbiology 03/2011; 157(Pt 6):1776-85. · 3.06 Impact Factor -
Article: Is the Campylobacter jejuni secretory protein Cj0069 a suitable antigen for serodiagnostics?
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ABSTRACT: Campylobacter spp. is the most common bacterial pathogen of gastroenteritis worldwide. Poultry is the main reservoir and consequently the main origin of infections for humans. As a consequence of a primary Campylobacter infection which typically manifests as diarrhea, there is an increased risk to suffer from post-infectious complications such as reactive arthritis, neuropathia, myositis or a Guillain-Barré Syndrome. Usually the verification of acute campylobacteriosis is made by stool culture. In contrast, post-infectious complications can be diagnosed by serological assays. Since most of them are based on whole cell lysates, an insufficient specificity results from cross-reactions between related species. Therefore, the use of recombinant antigens becomes more and more favorable. Campylobacter is able to secrete a number of proteins, which are amongst others necessary for cell invasion and therefore play a crucial role for virulence. One of these, Cj0069, has a similar specificity and sensitivity in the detection of anti-Campylobacter jejuni IgG compared to the well-established antigens OMP18 and P39. This makes it a suitable antigen for diagnosing C. jejuni post-infectious complications.European Journal of Microbiology and Immunology. 01/2011; 1(1):86-94. -
Article: Campylobacter jejuni proteins Cj0952c and Cj0951c affect chemotactic behaviour towards formic acid and are important for invasion of host cells.
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ABSTRACT: Campylobacter jejuni, an important food-borne bacterial pathogen in industrialized countries and in the developing world, is one of the major causes of bacterial diarrhoea. To identify genes which are important for the invasion of host cells by the pathogen, we screened altogether 660 clones of a transposon-generated mutant library based on the clinical C. jejuni isolate B2. Thereby, we identified a clone with a transposon insertion in gene cj0952c. As in the well-characterized C. jejuni strain NCTC 11168, the corresponding protein together with the gene product of the adjacent gene cj0951c consists of two transmembrane domains, a HAMP domain and a putative MCP domain, which together are thought to act as a chemoreceptor, designated Tlp7. In this report we show that genes cj0952c and cj0951c (i) are important for the host cell invasion of the pathogen, (ii) are not translated as one protein in C. jejuni isolate B2, contradicting the idea of a postulated read-through mechanism, (iii) affect the motility of C. jejuni, (iv) alter the chemotactic behaviour of the pathogen towards formic acid, and (v) are not related to the utilization of formic acid by formate dehydrogenase.Microbiology 10/2010; 156(Pt 10):3123-35. · 3.06 Impact Factor -
Article: Improved clinical laboratory identification of human pathogenic yeasts by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
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ABSTRACT: The key to therapeutic success with yeast infections is an early onset of antifungal treatment with an appropriate drug regimen. To do this, yeast species identification is necessary, but conventional biochemical and morphological approaches are time-consuming. The recent arrival of biophysical methods, such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), in routine diagnostic laboratories holds the promise of significantly speeding up this process. In this study, two commercially available MALDI-TOF MS species identification systems were evaluated for application in clinical diagnostics, using a geographically diverse collection of 1192 clinical yeast and yeast-like isolates. The results were compared with those of the classical differentiation scheme based on microscopic and biochemical characteristics. For 95.1% of the isolates, all three procedures consistently gave the correct species identification, but the rate of misclassification was greatly reduced in both MALDI-TOF MS systems. Furthermore, several closely related species (e.g. Candida orthopsilosis/metapsilosis/parapsilosis or Candida glabrata/bracarensis) could be resolved by both MALDI-TOF MS systems, but not by the biochemical approach. A significant advantage of MALDI-TOF MS over biochemistry in the recognition of isolates novel to the system was observed. Although both MALDI-TOF MS systems employed different approaches in the database structure and showed different susceptibilities to errors in database entries, these were negligible in terms of clinical usefulness. The time-saving benefit of MALDI-TOF MS over biochemical identification will substantially improve fungal diagnostics and patient treatment.Clinical Microbiology and Infection 10/2010; 17(9):1359-65. · 4.54 Impact Factor -
Article: Comparison between pp65 antigenemia assay and quantitative real-time polymerase chain reaction for detection of active cytomegalovirus infection in routine diagnostics.
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ABSTRACT: Real-time polymerase chain reaction (PCR) and pp65 antigenemia assay for the detection of active cytomegalovirus infection in immunocompromised patients experiencing neutropenia after bone marrow or kidney transplantation have been compared with a special focus on evaluability and embedment in daily routine diagnostics. Investigating 334 specimens from 97 patients, real-time PCR was shown to be the superior assay with regard to the parameters focused on.Diagnostic microbiology and infectious disease 10/2009; 65(2):192-5. · 2.45 Impact Factor -
Article: Campylobacter jejuni: a brief overview on pathogenicity-associated factors and disease-mediating mechanisms.
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ABSTRACT: Campylobacter jejuni has long been recognized as a cause of bacterial food-borne illness, and surprisingly, it remains the most prevalent bacterial food-borne pathogen in the industrial world to date. Natural reservoirs for this Gram-negative, spiral-shaped bacterium are wild birds, whose intestines offer a suitable biological niche for the survival and dissemination of C. jejuni Chickens become colonized shortly after birth and are the most important source for human infection. In the last decade, effective intervention strategies to limit infections caused by this elusive pathogen were hindered mainly because of a paucity in understanding the virulence mechanisms of C. jejuni and in part, unavailability of an adequate animal model for the disease. However, recent developments in deciphering molecular mechanisms of virulence of C. jejuni made it clear that C. jejuni is a unique pathogen, being able to execute N-linked glycosylation of more than 30 proteins related to colonization, adherence, and invasion. Moreover, the flagellum is not only depicted to facilitate motility but as well secretion of Campylobacter invasive antigens (Cia). The only toxin of C. jejuni, the so-called cytolethal distending toxin (CdtA,B,C), seems to be important for cell cycle control and induction of host cell apoptosis and has been recognized as a major pathogenicity-associated factor. In contrast to other diarrhoea-causing bacteria, no other classical virulence factors have yet been identified in C. jejuni. Instead, host factors seem to play a major role for pathogenesis of campylobacteriosis of man. Indeed, several lines of evidence suggest exploitation of different adaptation strategies by this pathogen depending on its requirement, whether to establish itself in the natural avian reservoir or during the course of human infection.International journal of medical microbiology: IJMM 09/2009; 300(4):205-11. · 2.80 Impact Factor -
Article: Short-term rifampicin pretreatment reduces inflammation and neuronal cell death in a rabbit model of bacterial meningitis.
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ABSTRACT: In bacterial meningitis, severe systemic and local inflammation causes long-term impairment and death of affected patients. The current antibiotic therapy relies on cell wall-active beta-lactam antibiotics, which rapidly sterilize the cerebrospinal fluid (CSF). However, beta-lactams inhibit cell wall synthesis, induce bacteriolysis, and thereby evoke a sudden release of high amounts of toxic and proinflammatory bacterial products. Because tissue damage in bacterial meningitis is the result of bacterial toxins and the inflammatory host response, any reduction of free bacterial compounds promises to prevent neuronal damage. In vitro experiments and randomized prospective animal study. University research laboratories. Streptococcus pneumoniae broth cultures and New Zealand White rabbits. We evaluated a concept to improve bacterial meningitis therapy in which a short-term pretreatment with the protein synthesis-inhibiting antibiotic rifampicin precedes the standard antibiotic therapy with ceftriaxone. First, logarithmically growing pneumococcal cultures were subdivided and exposed to different antibiotics. Then, rabbits suffering from pneumococcal meningitis were randomized to receive rifampicin pretreatment or ceftriaxone alone. In pneumococcal cultures, quantitative immunoblotting and real-time polymerase chain reaction revealed a reduced release of pneumolysin and bacterial DNA by rifampicin pretreatment for 30 minutes in comparison with ceftriaxone treatment alone. In vivo, a 1-hour rifampicin pretreatment reduced the release of bacterial products and attenuated the inflammatory host response, as demonstrated by decreased CSF levels of prostaglandin E2 and total protein and increased glucose CSF/plasma ratios. Rifampicin pretreatment reduced infection-associated neuronal apoptotic cell loss compared with ceftriaxone-treated controls. A short-term pretreatment with rifampicin reduced the beta-lactam-induced release of deleterious bacterial products, attenuated inflammation, and thereby decreased neuronal cell loss in experimental bacterial meningitis. This concept has the potential to reduce inflammation-associated neuronal injury in bacterial meningitis and should be evaluated in a clinical trial.Critical care medicine 08/2009; 37(7):2253-8. · 6.37 Impact Factor -
Article: Characterization and intracellular localization of putative Chlamydia pneumoniae effector proteins.
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ABSTRACT: We here describe four proteins of Chlamydia pneumoniae, which might play a role in host-pathogen interaction. The hypothetical bacterial proteins CPn0708 and CPn0712 were detected in Chlamydia pneumoniae-infected host cells by indirect immunofluorescence tests with polyclonal antisera raised against the respective proteins. While CPn0708 was localized within the inclusion body, CPn0712 was identified in the inclusion membrane and in the surrounding host cell cytosol. CPn0712 colocalizes with actin, indicating its possible interaction with components of the cytoskeleton. Investigations on CPn0809 and CPn1020, two Chlamydia pneumoniae proteins previously described to be secreted into the host cell cytosol, revealed colocalization with calnexin, a marker for the ER. Neither CPn0712, CPn0809 nor CPn1020 were able to inhibit host cell apoptosis. Furthermore, transient expression of CPn0712, CPn0809 and CPn1020 by the host cell itself had no effect on subsequent infection with Chlamydia pneumoniae. However, microarray analysis of CPn0712-expressing host cells revealed six host cell genes which were regulated as in host cells infected with Chlamydia pneumoniae, indicating the principal usefulness of heterologous expression to study the effect of Chlamydia pneumoniae proteins on host cell modulation.Medical Microbiology and Immunology 06/2008; 197(4):387-96. · 3.83 Impact Factor -
Article: Role of the plasmid-encoded tet(O) gene in tetracycline-resistant clinical isolates of Campylobacter jejuni and Campylobacter coli.
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ABSTRACT: The prevalence of tetracycline resistance, tetracycline MICs and tet(O) gene localization were investigated in 83 Campylobacter isolates from patients suffering from acute gastroenteritis in Germany. Combined biochemical and molecular markers identified 74 isolates (89 %) as Campylobacter jejuni, including seven atypical isolates that failed to hydrolyse hippurate, and nine isolates (11 %) as Campylobacter coli. Tetracycline resistance was detected in six out of nine Campylobacter coli isolates (67 %) and 13 out of 74 C. jejuni isolates (18 %). Low-level tetracycline resistance was observed for C. coli (MIC 16 microg ml(-1) for all strains), whereas C. jejuni showed high-level resistance (MIC >256 microg ml(-1) for all strains). Both low- and high-level tetracycline resistance was associated with the presence of the tet(O) gene. In C. jejuni, tet(O) was plasmid-encoded in 54 % of tetracycline-resistant isolates, whereas in C. coli, tet(O) appeared to be located on the chromosome.Journal of Medical Microbiology 06/2007; 56(Pt 6):833-7. · 2.50 Impact Factor
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2008–2011
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Universitätsmedizin Göttingen
- Department of Medical Microbiology
Göttingen, Lower Saxony, Germany
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