2024-03-28T23:14:26Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1292542022-12-14T15:47:51Zcom_10261_128com_10261_1com_10261_131com_10261_2col_10261_381col_10261_384
00925njm 22002777a 4500
dc
Harries, Eleonora
author
Carmona, Lourdes
author
Muñoz, Alberto
author
Ibeas, José I.
author
Read, Nick D.
author
Gandía Gómez, Mónica
author
Marcos López, José Francisco
author
2013
We have previously characterized the synthetic hexapeptide PAF26 as a cell-penetrating and non-lytic antifungal peptide that is active against Saccharomyces cerevisiae and filamentous fungi. Numerous cell wall (CW) proteins are glycosylated in fungi and many of these play important roles in fungal pathogenesis. In this study, we screened a collection of S. cerevisiae deletion mutants for protein glycosylation genes whose deletion altered the sensitivity to PAF26. Increased tolerance to PAF26 was observed in mutants with the following disrupted genes: PMT1-6, EOS1, ALG5, MNN1, MNN4 and MNN5. Significantly, genes coding for protein O-mannosyltransferase 2 (Pmt2p), which is responsible for the addition of the first mannosyl residue of O-linked carbohydrates, and for Eos1p, an enzyme involved in N-linked glycosylation of proteins, showed resistance to PAF26 and defects in CW integrity. Microscopic studies on the S. cerevisiae δ. eos1 deletion mutant demonstrated a blockage of peptide internalization by cells. Protoplasts lacking CWs interacted with the peptide, but were more resistant to peptide killing than cells possessing CWs due to a blockage in PAF26 internalization. Interestingly, protoplasts obtained from δ. eos1 behaved similarly to those of the parental strain. Collectively, these observations demonstrate that the CW is a positive factor that determines the internalization of the PAF26, and that Eos1p exerts its activity through the glycosylation of specific protein(s) involved in peptide internalization.
Fungal Genetics and Biology 58-59: 105-115 (2013)
http://hdl.handle.net/10261/129254
10.1016/j.fgb.2013.08.004
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100003359
Antimicrobial peptides
Cell walls
Melittin
Histatins
Protein glycosylation
Cell-penetrating peptides
Genes involved in protein glycosylation determine the activity and cell internalization of the antifungal peptide PAF26 in Saccharomyces cerevisiae