Potential use of peptides mimicking CRAC/CARC domains as antivirulence therapies to inhibit RTX toxins activities

In recent years, research efforts have increased to develop new therapeutics aimed at combating antibiotic-resistant bacterial infections. These efforts focus on inhibiting the virulence factors bacteria secrete to proliferate. This review aims to highlight the advances in these antivirulence therap...

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Main Author: Vanesa Herlax
Format: Article
Language:English
Published: Open Exploration 2024-11-01
Series:Exploration of Drug Science
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Online Access:https://www.explorationpub.com/uploads/Article/A100876/100876.pdf
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author Vanesa Herlax
author_facet Vanesa Herlax
author_sort Vanesa Herlax
collection DOAJ
description In recent years, research efforts have increased to develop new therapeutics aimed at combating antibiotic-resistant bacterial infections. These efforts focus on inhibiting the virulence factors bacteria secrete to proliferate. This review aims to highlight the advances in these antivirulence therapies, with a particular emphasis on those utilizing peptides to inhibit toxin activity. Specifically, we will review the mechanism of action of a group of toxins known as Repeat in ToXins (RTX) and the progress made regarding the use of peptides to inhibit their action. Notably, we will discuss the use of peptides mimicking either cholesterol recognition/interaction amino acid consensus (CRAC) or CARC motifs, which are similar to CRAC motifs but have the opposite orientation, to reduce their interaction with cholesterol in target cells. We will present results corresponding to the inhibition of three characteristic toxins of this group: HlyA from Escherichia coli, LtxA from Aggregatibacter actinomycetemcomitans, and CyaA from Bordetella pertussis. While these advances are very recent, they are promising for the development of new therapies. The advantage of this type of therapy is that it reduces the selective pressure for the growth of resistant bacteria.
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spelling doaj-art-b52f3a14dc664c9abf1277e13c49e2452025-02-08T03:28:18ZengOpen ExplorationExploration of Drug Science2836-76772024-11-012683685010.37349/eds.2024.00076Potential use of peptides mimicking CRAC/CARC domains as antivirulence therapies to inhibit RTX toxins activitiesVanesa Herlax0https://orcid.org/0000-0003-4218-8702Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CCT-La Plata, CONICET, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata 1900, ArgentinaIn recent years, research efforts have increased to develop new therapeutics aimed at combating antibiotic-resistant bacterial infections. These efforts focus on inhibiting the virulence factors bacteria secrete to proliferate. This review aims to highlight the advances in these antivirulence therapies, with a particular emphasis on those utilizing peptides to inhibit toxin activity. Specifically, we will review the mechanism of action of a group of toxins known as Repeat in ToXins (RTX) and the progress made regarding the use of peptides to inhibit their action. Notably, we will discuss the use of peptides mimicking either cholesterol recognition/interaction amino acid consensus (CRAC) or CARC motifs, which are similar to CRAC motifs but have the opposite orientation, to reduce their interaction with cholesterol in target cells. We will present results corresponding to the inhibition of three characteristic toxins of this group: HlyA from Escherichia coli, LtxA from Aggregatibacter actinomycetemcomitans, and CyaA from Bordetella pertussis. While these advances are very recent, they are promising for the development of new therapies. The advantage of this type of therapy is that it reduces the selective pressure for the growth of resistant bacteria.https://www.explorationpub.com/uploads/Article/A100876/100876.pdfrtx toxinsantivirulence therapiescrac/carc domainshlya of e. coli
spellingShingle Vanesa Herlax
Potential use of peptides mimicking CRAC/CARC domains as antivirulence therapies to inhibit RTX toxins activities
Exploration of Drug Science
rtx toxins
antivirulence therapies
crac/carc domains
hlya of e. coli
title Potential use of peptides mimicking CRAC/CARC domains as antivirulence therapies to inhibit RTX toxins activities
title_full Potential use of peptides mimicking CRAC/CARC domains as antivirulence therapies to inhibit RTX toxins activities
title_fullStr Potential use of peptides mimicking CRAC/CARC domains as antivirulence therapies to inhibit RTX toxins activities
title_full_unstemmed Potential use of peptides mimicking CRAC/CARC domains as antivirulence therapies to inhibit RTX toxins activities
title_short Potential use of peptides mimicking CRAC/CARC domains as antivirulence therapies to inhibit RTX toxins activities
title_sort potential use of peptides mimicking crac carc domains as antivirulence therapies to inhibit rtx toxins activities
topic rtx toxins
antivirulence therapies
crac/carc domains
hlya of e. coli
url https://www.explorationpub.com/uploads/Article/A100876/100876.pdf
work_keys_str_mv AT vanesaherlax potentialuseofpeptidesmimickingcraccarcdomainsasantivirulencetherapiestoinhibitrtxtoxinsactivities