Background: Cryptococcosis and cryptococcal meningitis, caused by infections, lead to approximately 180,000 deaths per year, primarily in developing countries. Individuals with compromised immune systems, e.g., due to HIV infection (AIDS) or chemotherapy, are particularly vulnerable. Conventional treatment options are often limited and can cause severe side effects. Therefore, this study aimed to investigate the antifungal effect of insect-derived proline-rich antimicrobial peptides (PrAMPs) against . These peptides are known for their low toxicity and their high efficacy in murine infection models, making them a promising alternative for treatment.
Results: A preliminary screening of the minimal inhibitory concentrations (MICs) of 20 AMPs, including the well-known PrAMPs Onc112, Api137, and Chex1Arg20 as well as the cathelicidin CRAMP against the strains 1841, H99, and KN99α revealed promising results, with MICs as low as 1.6 μmol/L. Subsequent investigations of selected peptides, determining their influence on fungal colony-forming units, confirmed their strong activity. The antifungal activity was affected by factors such as peptide net charge and sequence, with stronger effects at higher net charges probably due to better intracellular uptake confirmed by confocal laser scanning microscopy. Inactive scrambled peptides suggest a specific intracellular target, although scanning electron microscopy showed that PrAMPs also damaged the cell exterior for a low proportion of the cells. Possible pore formation could facilitate entry into the cytosol.
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http://dx.doi.org/10.3389/fmicb.2023.1328890 | DOI Listing |
Molecules
December 2024
Department of Immunobiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19 St., 20-033 Lublin, Poland.
Antimicrobial peptides (AMPs) constitute a large and diverse group of molecules with antibacterial, antifungal, antiviral, antiprotozoan, and anticancer activity. In animals, they are key components of innate immunity involved in fighting against various pathogens. Proline-rich (Pr) AMPs are characterized by a high content of proline (and arginine) residues that can be organized into Pro-Arg-Pro motifs.
View Article and Find Full Text PDFOpen Biol
December 2024
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
Proline-rich antimicrobial peptides (PrAMPs) have gained attention due to their antimicrobial properties and low cytotoxicity. B7-005, a small optimized PrAMP, exhibits a broader spectrum of activity than native PrAMPs, due to an antimicrobial mechanism based on inhibiting prokaryotic protein synthesis and destabilizing bacterial membranes. However, the toxicity and the efficacy of B7-005 remain poorly understood, so and microbiology and toxicology experiments were used to assess its suitability as an anti-infective agent.
View Article and Find Full Text PDFJ Invertebr Pathol
November 2024
Department of Biological Sciences and Biotechnology, Chungbuk National University, Chungbuk 28644, Republic of Korea. Electronic address:
J Med Chem
November 2024
Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
We recently showed that solid-phase peptide synthesis using racemic amino acids yields stereorandomized peptides comprising all possible diastereomers as homogeneous, single-mass products that can be purified by HPLC and that stereorandomization modulates activity, toxicity, and stability of membrane-disruptive cyclic and linear antimicrobial peptides (AMPs) and dendrimers. Here, we tested if stereorandomization might be compatible with target binding peptides with the example of the proline-rich AMP oncocin, which inhibits the bacterial ribosome. Stereorandomization of up to nine -terminal residues preserved ribosome binding and antibacterial effects including activities against drug-resistant bacteria and protected against serum degradation.
View Article and Find Full Text PDFEMBO Rep
November 2024
Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, 60612, USA.
Apidaecin 1b (Api), the first characterized Type II Proline-rich antimicrobial peptide (PrAMP), is encoded in the honey bee genome. It inhibits bacterial growth by binding in the nascent peptide exit tunnel of the ribosome after the release of the completed protein and trapping the release factors. By genome mining, we have identified 71 PrAMPs encoded in insect genomes as pre-pro-polyproteins.
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