At the beginning of my career I concentrated on the relationship between diagnosis and virulence in pathogenic fungi, particularly in Cryptococcus neoformans. We correlated melanin formation, which is one of the main diagnostic tools in this fungus, with its virulence and so we learned that melanin as a scavenger of hydroxyl radicals enabled the survival of this fungus in the infected tissue. In collaboration with the conservation laboratory of The Israel Museum and by using routine diagnostic methods we proved that the ancient parchment of the Aleppo Codex (Keter Aram Tzova) was damaged by fungi and not by fire. Occasionally we provided first descriptions of infections by fungal species not previously seen as human pathogens such as Aspergillus quadralineatus.
Recently I concentrated on developing novel antifungal agents and understanding their mechanism of action. Our current project deals with a newly developed group of thiazolidinedione derivatives that exhibited both anti-fungal and anti-biofilm activity. The most effective anti-biofilm compound was the TZD-8. Its anti-biofilm activity in Candida albicans involved yeast-to-hyphal form transition, hyphal morphology, cell wall morphology and composition, and sterol distribution. On the molecular level it modulated the expression of genes associated with biofilm formation, adhesion and filamentation (HWP1, ALS3, EAP1, UME6, RAS1, CST20, HST7, CPH1) that were down-regulated, while transcriptional repressors of filament formation (TUP1 and NRG) were dramatically upregulated. TZD-8 also presents anti-fungal and anti-biofilm effects in Cryptococcus neoformans by inhibiting the CDC25-phosphatase that triggers G2/M cell-cycle arrest.
Recent papers (2014):
J Antimicrob. Chemother. 69:416; PLoS One5:9(5):e93225; Cell 159:1168.
