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Published on: January 26, 2016
A synthetic peptide selectively kills only virulent Paracoccidioides brasiliensis yeasts
Erika Seki Kioshima1, Fabiana Aliperti, Juliana Terzi Maricato
1Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Abstract:
This work was conducted to identify virulence biomarkers for Paracoccidioides brasiliensis (Pb), the fungus responsible for Paracoccidioidomycosis (PCM), a systemic disease endemic in Latin America. Measurement of mortality showed that all B10.A mice were killed after 250 days by the virulent Pb18 isolate while only one of the mice that received the attenuated counterpart died. Also, number of lung CFUs from virulent Pb18 inoculated mice were much higher when these isolates were compared. Phage display methodology allowed selection of three phages that specifically bound to virulent Pb18. Variability of p04 phage binding to different Pb isolates were examples of variability of expression by the fungus of its binding molecule, strongly suggesting p04 as a biomarker of virulence. In vitro, its derived peptide pep04 killed only virulent fungi, and confocal microscopy showed that it was internalized only by the virulent isolate. Pep04 blocked establishment of Pb infection in mice and virulent Pb18 pre-incubated with p04 showed significantly inhibited lung infection. Furthermore, infected mice treated with p04 showed highly significant reduction in lung CFUs. These findings firmly establish p04 as a biomarker of Pb virulence. Therefore, after proper peptide engineering, p04 may become a useful adjuvant for the distressing treatment of PCM.
Insights
Researchers identified p04 as a biomarker for Paracoccidioides brasiliensis (Pb) virulence. This peptide effectively targets and inhibits virulent fungal strains, offering potential for new Paracoccidioidomycosis (PCM) treatments.
Area of Science:
- Mycology
- Infectious Diseases
- Biomarker Discovery
Background:
- Paracoccidioides brasiliensis (Pb) causes Paracoccidioidomycosis (PCM), a significant endemic disease in Latin America.
- Identifying virulence factors is crucial for developing effective therapeutic strategies against Pb.
Purpose of the Study:
- To identify and characterize novel virulence biomarkers for Paracoccidioides brasiliensis.
- To evaluate the therapeutic potential of identified biomarkers against Pb infection.
Main Methods:
- Utilized phage display methodology to select specific binding phages against virulent Pb isolates.
- In vitro and in vivo assays were performed to assess the efficacy of the derived peptide (pep04).
- Confocal microscopy was employed to study peptide internalization.
Main Results:
- Phage display identified p04 phage that specifically binds to virulent Pb strains.
- The derived peptide, pep04, demonstrated selective killing of virulent Pb in vitro and blocked infection establishment in vivo.
- Treatment with pep04 significantly reduced lung fungal burden in infected mice.
Conclusions:
- p04 is established as a reliable biomarker for Pb virulence.
- Engineered p04 holds promise as an adjuvant therapy for Paracoccidioidomycosis.
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