Application of a low molecular weight antifungal protein from Penicillium chrysogenum (PAF) to treat pulmonary aspergillosis in mice

Abstract

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.

In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis

“…This result proves the potential effectiveness of NFAP2 monotherapy in the treatment of superficial yeast infections. Until now, the in vivo applicability of crAFPs as antifungal agents was investigated only with PAF (34,35). Since PAF effectively inhibits the growth of human-pathogenic filamentous fungi (23), its therapeutic potential was tested by Palicz et al in a murine pulmonary aspergillosis model (35).…”

Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum: A comparative study of PAF and PAFB

“…Furthermore, Palicz and co-workers (2016) showed in a follow-up study that PAF was similarly effective as amphotericin B and that mildly prolonged the survival of a mouse model suffering from invasive pulmonary aspergillosis when administered intraperitoneally. Notably, the efficacy could be significantly increased when PAF was applied in combination with amphotericin B [76].…”

Physiological background of the remarkably high Cd2+ tolerance of the Aspergillus fumigatus Af293 strain

“…Mice were immunosuppressed with 200 mg kg −1 cyclophosphamide 3 days before infection and 1, 4, and 7 days after infection. Infection was carried out by the instillation of 50 µl of freshly made suspension containing 7 × 10 6 conidia . The survival of the mice was monitored for 10 days.…”

“…After 10 days, animals were killed by cervical dislocation. The lungs of the mice were examined histologically to detect infection .…”