A.M.S. Al Hatmi
- Phylogeny, diagnostics and antifungal susceptibility of clinically relevant Fusarium species
- Award date
- 21 December 2016
- Number of pages
- Document type
- PhD thesis
- Faculty of Science (FNWI)
- Institute for Biodiversity and Ecosystem Dynamics (IBED)
During the last decades, human infections by Fusarium species (Fungi) have shown global increase, both in immunocompromised and in immunocompetent patients. These infections can be classified in four classes: (1) superficial infections of skin and nails, (2) keratitis of the cornea, and (3) deep localized and (4) disseminated infections.
In this PhD project we addressed some of the major problems connected to human fusarioses. (1) We first identified and delimited the species that are etiological agents of different types of infections. Our molecular and phylogenetic studies were performed by using multi-gene analysis of BT, TEF1, TOPO1, PGK, RPB2 and ITS. The results confirmed that Fusarium is monophyletic. (2) Subsequently we aimed to understand which properties are essential in virulence of these opportunists, given the fact that the great majority of their saprobic and plant-pathogenic relatives are not known to be involved in human disease. (3) Furthermore, we developed diagnostic tools for the clinical laboratory. Knowing that current culture-dependent characterization methods for deep infections are often too slow, we introduced faster DNA-based or whole cell-based identification techniques such as MALDI-TOF MS to characterize these species. MALDI-TOF MS approach can be performed with minimal amounts of sample and takes only 15−30 minutes and are cheap. AFLP fingerprinting has successfully been applied in this study with a large numbers of clinical and environmental strains. Our findings indicate that AFLP analysis and MLSA analysis provide high resolution data allowing discrimination between Fusarium species and genotypes. (4) Finally, once etiological agents have been properly recognized and identified, we tested susceptibility profiles of most of opportunistic Fusarium against a panel of anitifungal compounds. In vitro antifungal testing showed that amphotericin B and voriconazole were the antimycotics with the best overall in vitro activity, followed by posaconazole. In vitro combination activity of natamycin alone and in combination with voriconazole was judged optimal for Fusarium keratitis and showed 70% synergism.
- Research conducted at: Universiteit van Amsterdam
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