Doctoral Researchers

 
Jaradat, Sameh

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JSMC Fellow

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Institute/Dep.
University Hospital Jena
Dept. for Dermatology
PhD Project:

Defensins and infectious skin diseases

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Abstract: Most living organisms are constantly exposed to potentially harmful pathogens through contact, ingestion and inhalation. Endogenous peptides provide fast and effective means of defence...
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... against pathogens (Barra and Simmaco, 1995; Lehrer and Ganz, 1999; Reddy et al., 2004). Defensins are small cysteine-rich cationic peptides that have antimicrobial properties against many gram-positive and gram-negative bacteria as well as some fungi and viruses (Zeya and Spitznagel, 1966; Ganz et al., 1985; Ganz and Lehrer, 1995). Two classes of human defensins, ? and ?, have been identified according to placement pattern and connectivity of cysteine residues. Cells of the immune system contain these peptides to assist in killing microbes by creating pores or disrupting the microbial cell membrane allowing the release of their cellular contents (White et al., 1995; Hoover et al., 2000). ?-Defensins are expressed by granulocytes, certain lymphocytes, and intestinal Paneth cells; while ?-defensins are expressed by epithelial cells (Harder et al., 1997, 2001; Ouellette and Bevins, 2001). High concentrations of ?-defensins have been found in extracts of the scales of psoriasis patients (Hoover et.al., 2001), that may account for their low rate of skin infections. Moreover, psoriasis has been shown to be associated with increased ?-defensin gene copy number (Hollox et al., 2008). Complex gene expression changes, gene polymorphisms, and environmental factors play a key role in the predisposition to diseases. So far, an association of ?-defensin-1 gene polymorphisms with Pseudomonas aeruginosa airway colonization in cystic fibrosis has been reported (Tesse et al., 2008). Pseudomonas is a genus of gram-negative gamma proteobacteria. Pseudomonas aeruginosa is increasingly recognized as an emerging opportunistic pathogen of clinical relevance, for example the bacterial infection in cystic fibrosis patients is limited to a relatively restricted spectrum of pathogens of which P. aeruginosa represents the most prevalent organism (Burns et al., 2001). On the other hand, several different epidemiological studies indicate that antibiotic resistance is increasing in clinical isolates (Van Eldere, 2003). Staphylococcus epidermidis, gram-positive cocci arranged in clusters, is frequently causing infections in patients whose immune system is compromised. S. epidermidis often shows resistance to a wide variety of antibiotics, including penicillin and methicillin. Furthermore, fungal skin infections cause a wide range of diseases in humans. Dermatophytes, which primarily affect the stratum corneum, cause erythema and scaling of the skin. A common example is Tinea versicolor, a fungal infection that affects the skin of young people. Jensen et al (2007) observed profound changes in skin structure and barrier function, epidermal proliferation, and differentiation including pronounced ?-defensin-2 expression in Tinea corporis. This study will address the question whether variations in defensin gene copy number does influence the individual patient susceptibility to infectious skin diseases.
 
 
Jo, Emeraldo

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FungiNet Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group:
Infection Biology
PhD Project:

Mechanisms of adhesion and modulation of human immune cells by Candida albicans

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Abstract: The human pathogenic yeast Candida albicans (C. albicans) responds and inhibits host innate as well as adaptive immune reactions. This project aims at elucidating the mechanisms of...
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... immune responses by human monocytes and macrophages to C. albicans. Novel microbial proteins will be defined that alone or together with recruited human plasma proteins modulate opsonizastion and cell interaction. Complement cleavage products are the natural ligands of complement receptors CR3 and CR4 expressed on human monocytes and macrophages. The characterization of the molecular and the cellular interplay, on the level of single molecules and cells, will be carried out and developed into a bioinformatics-based infection model, that will offer novel theapeutic targets for treatment.