Tarek Moussa

Iron is essential for a wide range of cellular processes. Here we show that the bZIP-type regulator HapX is indispensable for the transcriptional remodeling required for adaption to iron starvation in the opportunistic fungal pathogen Aspergillus fumigatus. HapX represses iron-dependent and mitochondrial-localized activities including respiration, TCA cycle, amino acid metabolism, iron-sulfur-cluster and heme biosynthesis. In agreement with the impact on mitochondrial metabolism, HapX-deficiency decreases resistance to tetracycline and increases mitochondrial DNA content. Pathways positively affected by HapX include production of the ribotoxin AspF1 and siderophores, which are known virulence determinants. Iron starvation causes a massive remodeling of the amino acid pool and HapX is essential for the coordination of the production of siderophores and their precursor ornithine. Consistent with HapX-function being limited to iron depleted conditions and A. fumigatus facing iron starvation in the host, HapX-deficiency causes significant attenuation of virulence in a murine model of aspergillosis. Taken together, this study demonstrates that HapX-dependent adaption to conditions of iron starvation is crucial for virulence of A. fumigatus.

Due to the significance of the antimicrobial peptides as innate immune effectors, in this study, a novel bovine antimicrobial peptide and its antimicrobial spectrum were described. RNA isolation from various tissues and RT-PCR were conducted. The DCD-like peptide was synthesized, and its antimicrobial effect was analyzed. The bovine dermcidin-like gene contains 5 exons intermittent by 4 introns. Bovine DCD-like mRNA was 398 bp with ORF size of 336 bp. Bovine DCD-like was expressed in skin and blood. Analysis of amino acid compositions showed that cysteine was repeated six times, which indicates the presence of 3 disulfide bonds that play a role in the peptide stability. Bovine DCD-like had an antimicrobial effect on Enterococcus faecalis, Streptococcus bovis, and  Staphylococcus epidermidis, which was highest at 50 and 100 µg/ml. The effect on Candida albicans and Escherichia coli was slightly low. In Staphylococcus aureus, the activity of bovine DCD-like was affected greatly at pH 4.5 and 5.5. The optimum salt concentrations were 50 and 100 mM with E. coli and all other bacterial strains, respectively. In C. albicans, the activity of bovine DCD-like decreased with increasing pH regardless of the concentration of NaCl. The pH 6.5 of the sweat buffer was optimum for the activity of bovine DCD-like. Finally, it was concluded that the bovine DCD-like gene expressed in skin cells and the DCD-like peptide secreted into the sweat, had high antimicrobial activities against many Gram-positive and -negative strains, as well as yeast-like fungus.