Antimicrobial peptides selectively target malaria parasites by a cholesterol-dependent mechanism

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00618754" target="_blank" >RIV/61388963:_____/25:00618754 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.jbc.2025.108298" target="_blank" >https://doi.org/10.1016/j.jbc.2025.108298</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jbc.2025.108298" target="_blank" >10.1016/j.jbc.2025.108298</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Antimicrobial peptides selectively target malaria parasites by a cholesterol-dependent mechanism

Popis výsledku v původním jazyce

Hundreds of thousands die annually from malaria caused by Plasmodium falciparum (Pf), with the emergence of drug-resistant parasites hindering eradication efforts. Antimicrobial peptides (AMPs) are known for their ability to disrupt pathogen membranes without targeting specific receptors, thereby reducing the chance of drug resistance. However, their effectiveness and the biophysical mechanisms by which they target the intracellular parasite remain unexplored. Here, by using native and synthetic AMPs, we discovered a selective mechanism that underlies the antimalarial activity. Remarkably, the AMPs exclusively interact with Pf-infected red blood cells, disrupting the cytoskeletal network and reaching the enclosed parasites with correlation to their activity. Moreover, we showed that the unique feature of reduced cholesterol content in the membrane of the infected host makes Pf-infected red blood cells susceptible to AMPs. Overall, this work highlights the Achilles’ heel of malaria parasite and demonstrates the power of AMPs as potential antimalarial drugs with reduced risk of resistance.

Název v anglickém jazyce

Antimicrobial peptides selectively target malaria parasites by a cholesterol-dependent mechanism

Popis výsledku anglicky

Hundreds of thousands die annually from malaria caused by Plasmodium falciparum (Pf), with the emergence of drug-resistant parasites hindering eradication efforts. Antimicrobial peptides (AMPs) are known for their ability to disrupt pathogen membranes without targeting specific receptors, thereby reducing the chance of drug resistance. However, their effectiveness and the biophysical mechanisms by which they target the intracellular parasite remain unexplored. Here, by using native and synthetic AMPs, we discovered a selective mechanism that underlies the antimalarial activity. Remarkably, the AMPs exclusively interact with Pf-infected red blood cells, disrupting the cytoskeletal network and reaching the enclosed parasites with correlation to their activity. Moreover, we showed that the unique feature of reduced cholesterol content in the membrane of the infected host makes Pf-infected red blood cells susceptible to AMPs. Overall, this work highlights the Achilles’ heel of malaria parasite and demonstrates the power of AMPs as potential antimalarial drugs with reduced risk of resistance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Svazek periodika

301

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

19

Strana od-do

108298

Kód UT WoS článku

001459363600001

EID výsledku v databázi Scopus

2-s2.0-105000872211