Application of a low molecular weight antifungal protein from Penicillium chrysogenum (PAF) to treat pulmonary aspergillosis in mice.
PAF, a small antifungal protein from Penicillium chrysogenum, inhibits the growth of several pathogenic filamentous fungi, including members of the Aspergillus genus. PAF has been proven to have no toxic effects in vivo in mice by intranasal application. To test its efficacy against invasive pulmonary aspergillosis (IPA), experiments were carried out in mice suffering from IPA. Adult mice were immunosuppressed and then infected with Aspergillus fumigatus. After stable infection, the animals were inoculated with PAF intranasally at a concentration of 2.7 mg/kg twice per day. At this concentration-which is highly toxic in vitro to A. fumigatus-the mortality of the animals was slightly delayed but finally all animals died. Histological examinations revealed massive fungal infections in the lungs of both PAF-treated and untreated animal groups. Because intranasally administered PAF was unable to overcome IPA, modified and combined therapies were introduced. The intraperitoneal application of PAF in animals with IPA prolonged the survival of the animals only 1 day. Similar results were obtained with amphotericin B (AMB), with PAF and AMB being equally effective. Combined therapy with AMB and PAF-which are synergistic in vitro-was found to be more effective than either AMB or PAF treatment alone. As no toxic effects of PAF in mammals have been described thus far, and, moreover, there are so far no A. fumigatus strains with reported inherent or acquired PAF resistance, it is worth carrying out further studies to introduce PAF as a potential antifungal drug in human therapy.
Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen H-4012, Hungary.
Zoltán
Z
Palicz
Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen H-4012, Hungary.
Tamás
T
Gáll
Department of Biotechnology and Microbiology, Faculty of Science and Technology, University of Debrecen, Debrecen H-4032, Hungary.
Éva
É
Leiter
Department of Pathology, Kenézy Gyula Hospital, Debrecen H-4031, Hungary.
Sándor
S
Kollár
Department of Pathology, Kenézy Gyula Hospital, Debrecen H-4031, Hungary.
Ilona
I
Kovács
Department of Laboratory Medicine, Medical Faculty, University of Debrecen, Debrecen H-4012, Hungary.
Kornél
K
Miszti-Blasius
Department of Biotechnology and Microbiology, Faculty of Science and Technology, University of Debrecen, Debrecen H-4032, Hungary.
István
I
Pócsi
Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen H-4012, Hungary.
László
L
Csernoch
Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen H-4012, Hungary.
Péter
P
Szentesi
D000281:Administration, Intranasal; D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005656:Fungal Proteins / Q000627:therapeutic use*; D006801:Humans; D016867:Immunocompromised Host; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy*; D051379:Mice; D010408:Penicillium chrysogenum / Q000737:chemistry*
D000935:Antifungal Agents; D005656:Fungal Proteins; C097832:PAF protein, Penicillium chrysogenum; D000666:Amphotericin B