Publications (93) View all

  • Article: Adenosine in the inflamed gut: a Janus faced compound.
    A B Estrela, W-R Abraham
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    ABSTRACT: The purine ribonucleoside adenosine (Ado) has been recognized for its regulatory functions in situations of cellular stress like ischemia, hypoxia and inflammation. The importance of extracellular Ado as a modulator in the immune system is a theme of great appreciation and the focus of recent increasing interest in the field of gastrointestinal inflammation. In this review, the different aspects of Ado signaling during inflammatory responses in the gut are discussed, considering the contribution of the four known Ado receptors (ARs; A(1), A(2A), A(2B), and A(3)), their mechanisms and expression patterns. Activation of these receptors in epithelial cells as well as in immune cells recruited to the inflamed intestinal mucosa determines the overall effect, ranging from a protective, anti-inflammatory modulation to a strong pro-inflammatory induction. Here we present the current advances in agonists and antagonists development and their potential therapeutic application studied in animal models of intestinal inflammation. In addition, alternative complementary approaches to manipulate such a complex signaling system are discussed, for example, the use of AR allosteric modulators or interference with Ado metabolism. Special features of the gut environment are taken into account: the contribution of diet components; the involvement of Ado in intestinal infections; the interactions with the gut microbiome, particularly, the recent exciting finding that an intestinal bacterium can directly produce extracellular Ado in response to host defense mechanisms in an inflammation scenario. Understanding each component of this dynamic system will broaden the possibilities for applying Ado signaling as a therapeutic target in gut inflammation.
    Current Medicinal Chemistry 01/2011; 18(18):2791-815. · 4.86 Impact Factor
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    Article: Microbial diversity of supra- and subgingival biofilms on freshly colonized titanium implant abutments in the human mouth.
    W Heuer, M Stiesch, W R Abraham
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    ABSTRACT: Supra- and subgingival biofilm formation is considered to be mainly responsible for early implant failure caused by inflammations of periimplant tissues. Nevertheless, little is known about the complex microbial diversity and interindividual similarities around dental implants. An atraumatic assessment was made of the diversity of microbial communities around titanium implants by single strand conformation polymorphism (SSCP) analysis of the 16S rRNA gene amplicons as well as subsequent sequence analysis. Samples of adherent supra- and subgingival periimplant biofilms were collected from ten patients. Additionally, samples of sulcusfluid were taken at titanium implant abutments and remaining teeth. The bacteria in the samples were characterized by SSCP and sequence analysis. A high diversity of bacteria varying between patients and within one patient at different locations was found. Bacteria characteristic for sulcusfluid and supra- and subgingival biofilm communities were identified. Sulcusfluid of the abutments showed higher abundance of Streptococcus species than from residual teeth. Prevotella and Rothia species frequently reported from the oral cavity were not detected at the abutments suggesting a role as late colonizers. Different niches in the human mouth are characterized by specific groups of bacteria. Implant abutments are a very valuable approach to study dental biofilm development in vivo.
    European Journal of Clinical Microbiology 10/2010; 30(2):193-200. · 2.86 Impact Factor
  • Article: Microbial Oxidation of Geranylacetone and Geranyloxycoumarin, Aurapten
    A. Müller, W. R. Abraham, K. Kieslich
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    ABSTRACT: Geranylacetone and geranyloxycoumarin (aurapten) were investigated with 14 selected microorganisms for ω-hydroxylation and epoxydation of the subterminal double bond. Trichoderma koningii and Verticillium theobromae are in principal useable for both reactions of geranyacetone. Although the yields of these preferably intended reactions were low, while ω-1-, ω-3-, ω-4-hydroxylations partially combined with reductive side reactions take place, the results gave an insight in the different pathways of oxidations dependent on the microorganism used. In contrast aurapten is transformed in relatively high yield to the E- or/and Z-configurated ω-alcohols (auraptenols) and to the aurapten-6,7-epoxide. The exclusively useable microorganisms for the oxidation of aurapten selected from the 237 strains tested were Nocardia alba and Bacillus cereus, which both formed enantioselectively the naturally configurated epoxyaurapten R-(+)-[6′,7′-epoxy-3′,7′-dimethyl-2′ octenyl]-7-oxycoumarin in yields of 10.5% respectively 21% of excellent optical purity of 99%ee.
    Bulletin des Sociétés Chimiques Belges. 08/2010; 103(7‐8):405 - 423.
  • Article: Microbiological Hydroxylation and N-Oxidation of Cinchona Alkaloids
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    ABSTRACT: Biotransformations of several structurally related cinchona alkaloids were investigated, mimicking mammalian metabolism. Quinine was oxidized to the 1-N-oxide and 1′-N-oxide by Microsporum gypseum, whereas Cunninghamella echinulata yielded the known 3-hydroxy-quinine. Xylaria digitata and Mycobacterium smegmatis oxidized the 1-N of quinidine whereas Mycobacterium gypseum formed the 1-N-oxide of hydroquinidine. No microorganism was found to attack cinchonine. The 1-N-oxide of cinchonidine was obtained with Pellicularia filamentosa. The so far unknown 3-hydroxy-cinchonidine was formed by Rhizopus arrhizus ATTC 10260 and ATCC 11145. As the metabolites could be isolated in yields of up to 9%, these biotransformations offer a method for preparative use.
    07/2009; 8(1):47-58.
  • Article: Bacterial community dynamics during biostimulation and bioaugmentation experiments aiming at chlorobenzene degradation in groundwater.
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    ABSTRACT: A set of microcosm experiments was performed to assess different bioremediation strategies, i.e., biostimulation and bioaugmentation, for groundwater contaminated with chlorobenzenes. The biodegradative potential was stimulated either by the supply of electron acceptors (air, (NO3-), to increase the activity of the indigenous bacterial community, or by the addition of aerobic chlorobenzene-degrading bacteria (Pseudomonas putida GJ31, Pseudomonas aeruginosa RHO1, Pseudomonas putida F1deltaCC). Experiments were performed with natural groundwater of the aquifer of Bitterfeld, which had been contaminated with 1,2-dichlorobenzene (1,2-DCB), 1,4-dichlorobenzene (1,4-DCB), and chlorobenzene (CB). The microcosms consisted of airtight glass bottles with 800 mL of natural groundwater and were incubated under in situ temperature (13 degrees C). Behavior of the introduced strains within the indigenous bacterial community was monitored by fluorescent in situ hybridization (FISH) with species-specific oligonucleotides. Dynamics of the indigenous community and the introduced strains within the microcosms were followed by single-strand conformation polymorphism (SSCP) analysis of 16S rDNA amplicons obtained from total DNA of the microbial community. An indigenous biodegradation potential under aerobic as well as anaerobic denitrifying conditions was observed accompanied by fast and specific changes in the natural bacterial community composition. Augmentation with P. aeruginosa RHO1 did not enhance bio-degradation. In contrast, both P. putida GJ31 as well as P. putida F1deltaCC were capable of growing in groundwater, even in the presence of the natural microbial community, and thereby stimulating chlorobenzene depletion. P. putida GJ31 disappeared when the xenobiotics were depleted and P. putida F1deltaCC persisted even in the absence of CB. Detailed statistical analyses revealed that community dynamics of the groundwater microbiota were highly reproducible but specific to the introduced strain, its inoculum size, and the imposed physicochemical conditions. These findings could contribute to the design of better in situ bioremediation strategies for contaminated groundwater.
    Microbial Ecology 09/2003; 46(2):161-76. · 2.91 Impact Factor

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