THE PENICILLIUM CHRYSOGENUM ANTIFUNGAL PROTEIN (PAF) CAN BE A PROMISING ANTIMYCOTIC CANDIDATE

Leiter, E., Palicz, Z., Gáll, T., Kollár, S., Kovács, I., Miszti-Blasius, K., Pócsi, I., Csernoch, L., Szentesi, P.

Department of Biotechnology and Microbiology, University of Debrecen, Debrecen, Hungary

Abstract

Invasive pulmonary aspergillosis (IPA) is a difficult to treat, often fatal infection in immunocompromised patients. IPA is caused mainly by Aspergillus fumigatus among various Aspergillus species. Unfortunately, Aspergillus fumigatus can develop resistance against the recently used antifungal agents, like voriconazole, posaconazole, amphotericin B (AMB). Therefore, there is an urgent need for new, effective antimycotics. The small molecular mass antifungal proteins produced generally by eukaryotes including plants, animals and fungi can be good candidates for the treatment of diseases caused by pathogenic fungi. Their future applicability is supported by their outstanding stability, the lack of any cytotoxic effect on mammalian cells and the rare development of resistance. The penicillin producer Penicillium chrysogenum abundantly secretes a small molecular mass antifungal protein, namely PAF, which has growth inhibitory effect on some human pathogenic fungi including Aspergillus fumigatus. In this study we tested the in vivo antifungal activity of PAF against IPA in mice. Combined intraperitoneal administration with AMB - which are synergistic in vitro - prolonged the survival of animals suffering from IPA. Hopefully, in the future PAF – AMB combination may find its application in the treatment of IPA in human medicine. This project was supported by the Hungarian Scientific Research Fund (OTKA CK77515 and NKFIH K112181), Hungarian Ministry of Education (TÁMOP-4.2.1/B-09/1/KONV-2010-0007, TÁMOP-4.2.2/B-10/1-2010-0024 and TÁMOP-4.2.2. A-11/1/KONV-2012-0025).

Keywords: Penicillium chrysogenum antifungal protein, invasive pulmonary aspergillosis.