GHTM

Global Health and Tropical Medicine

  • GHTM
    • Vision
    • Mission
    • Governance
    • Scientific Advisory Board
  • News
    • Outreach
    • Events
      • GHTM Sessions
      • Workshops
    • Articles
    • Jobs
  • Research
    • Cross-cutting issues
      • Global Pathogen Dispersion and Population Mobility
      • Drug Discovery and Drug Resistance
      • Diagnostics
      • Public Health Information
      • Fair Research Partnerships
    • Research Groups
      • PPS – Population health, policies and services
      • THOP – TB, HIV and opportunistic diseases and pathogens
      • VBD – Vector borne diseases and pathogens
      • IHC – Individual health care
    • Research in numbers
      • 2020
      • 2019
      • 2018
      • 2017
    • Projects
      • Ongoing Projects
    • Members
      • Population health, policies and services
        • PPS PhD members
        • PPS non PhD members
      • TB, HIV and opportunistic diseases and pathogens
        • THOP PhD members
        • THOP non PhD members
      • Vector-borne diseases and pathogens
        • VBD PhD members
        • VBD non PhD members
      • Individual Health Care
        • IHC PhD members
        • IHC non PhD members
      • Technical / administrative support
  • Publications
  • Education
    • Master Theses
    • PhD Theses
  • Services
Home / Publicações / Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity

Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity

  • Autores: Tatyana Almeida Tavella, Noeli Soares Melo da Silva, Natalie Spillman, Ana Carolina Andrade Vitor Kayano, Gustavo Capatti Cassiano, Adrielle Ayumi Vasconcelos, Antônio Pedro Camargo, Djane Clarys Baia da Silva, Diana Fontinha, Luis Carlos Salazar Alvarez, Letícia Tiburcio Ferreira, Kaira Cristina Peralis Tomaz, Bruno Junior Neves, Ludimila Dias Almeida, Daniel Youssef Bargieri, Marcus Vinicius Guimarães de Lacerda, Pedro Vítor Lemos Cravo, Per Sunnerhagen, Miguel Prudêncio, Carolina Horta Andrade, Stefanie Costa Pinto Lopes, Marcelo Falsarella Carazzolle, Leann Tilley, Elizabeth Bilsland, Júlio César Borges, Fabio Trindade Maranhão Costa
  • Ano de Publicação: 2021
  • Journal: ACS Infectious Diseases, 7(4), pp 759 - 7769
  • Link: https://doi.org/10.1021/acsinfecdis.0c00454

ABSTRACT

Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, Plasmodium falciparum (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis. Mechanistically, violacein binds Pf chaperones, PfHsp90 and PfHsp70-1, compromising the latter’s ATPase and chaperone activities. Additionally, violacein-treated parasites exhibited increased protein unfolding and proteasomal degradation. The uncoupling of the parasite stress response reflects the multistage growth inhibitory effect promoted by violacein. Despite evidence of proteotoxic stress, violacein did not inhibit global protein synthesis via UPR activation—a process that is highly dependent on chaperones, in agreement with the notion of a violacein-induced proteostasis collapse. Our data highlight the importance of a functioning chaperone–proteasome system for parasite development and differentiation. Thus, a violacein-like small molecule might provide a good scaffold for development of a novel probe for examining the molecular chaperone network and/or antiplasmodial drug design.

 

KEYWORDS

malaria; chaperone inhibitor; chemogenomics; violacein; proteostasis.

Share this:

  • Click to share on Facebook (Opens in new window)
  • Click to share on Twitter (Opens in new window)
  • Click to share on LinkedIn (Opens in new window)
  • Click to share on Pinterest (Opens in new window)
  • Click to share on WhatsApp (Opens in new window)
  • Click to print (Opens in new window)

Events

GHTM Webinar – Host-Pathogen Interactions: Host-targeted therapies as a tool to overcome antimicrobial resistance

   
Ler mais

Share this:

  • Click to share on Facebook (Opens in new window)
  • Click to share on Twitter (Opens in new window)
  • Click to share on LinkedIn (Opens in new window)
  • Click to share on Pinterest (Opens in new window)
  • Click to share on WhatsApp (Opens in new window)
  • Click to print (Opens in new window)

GHTM Group leaders were on mission in Cape Verde

Between 5th and 11th June, the GHTM-IHMT Group leaders Maria do Rosário Martins (Population health, … [Read More...]

Professor Luís Sambo is the new member of Partnership for Maternal, Newborn & Child Health

In his capacity of member of Global Health and Tropical Medicine (GHTM), Sambo accepted the … [Read More...]

Rodent malaria genetics as a model to unravel the mechanisms of drug resistance in malaria parasites of humans

Pedro Cravo, GHTM Cross-cutting Issue Drug Discovery & Resistance facilitator, has just … [Read More...]

Immigrants are more vulnerable to the socioeconomic impact caused by the COVID-19 pandemic

A study published in Frontiers in Public Health, led by a GHTM researcher, shows that immigrants are … [Read More...]

IHMT | GHTM – APPLICATIONS ARE OPEN!

IHMT | GHTM - Applications are open for three research vacancies:   One position - PhD … [Read More...]

IS_MIRRI21 “Executive Director”

Applications are open from July 2 to July 22, 2020. … [Read More...]

About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

Contacts

Rua da Junqueira, 100
1349-008 Lisboa
Portugal
+351 213 652 600
+351 213 632 105

  • Facebook
  • YouTube

Subscribe Newsletter

  • How to get to GHTM/IHMT
  • GHTM Sessions
  • Research Groups
  • Cross-cutting issues
© Copyright 2022 IHMT-UNL Todos os Direitos Reservados.
  • Universidade Nova de Lisboa
  • Fundação para a Ciência e a Tecnologia

    Project UID/Multi/04413/2013

 

Loading Comments...