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Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors
Throughout its known history, the gram-negative bacterium Chlamydia pneumoniae has remained a challenging target for antibacterial chemotherapy and drug discovery. Owing to its well-known propensity for persistence and recent reports on antimicrobial resistence within closely related species, new ap...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192526/ https://www.ncbi.nlm.nih.gov/pubmed/27916800 http://dx.doi.org/10.3390/microorganisms4040043 |
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author | Hanski, Leena Vuorela, Pia |
author_facet | Hanski, Leena Vuorela, Pia |
author_sort | Hanski, Leena |
collection | PubMed |
description | Throughout its known history, the gram-negative bacterium Chlamydia pneumoniae has remained a challenging target for antibacterial chemotherapy and drug discovery. Owing to its well-known propensity for persistence and recent reports on antimicrobial resistence within closely related species, new approaches for targeting this ubiquitous human pathogen are urgently needed. In this review, we describe the strategies that have been successfully applied for the identification of nonconventional antichlamydial agents, including target-based and ligand-based virtual screening, ethnopharmacological approach and pharmacophore-based design of antimicrobial peptide-mimicking compounds. Among the antichlamydial agents identified via these strategies, most translational work has been carried out with plant phenolics. Thus, currently available data on their properties as antichlamydial agents are described, highlighting their potential mechanisms of action. In this context, the role of mitogen-activated protein kinase activation in the intracellular growth and survival of C. pneumoniae is discussed. Owing to the complex and often complementary pathways applied by C. pneumoniae in the different stages of its life cycle, multitargeted therapy approaches are expected to provide better tools for antichlamydial therapy than agents with a single molecular target. |
format | Online Article Text |
id | pubmed-5192526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-51925262017-01-03 Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors Hanski, Leena Vuorela, Pia Microorganisms Review Throughout its known history, the gram-negative bacterium Chlamydia pneumoniae has remained a challenging target for antibacterial chemotherapy and drug discovery. Owing to its well-known propensity for persistence and recent reports on antimicrobial resistence within closely related species, new approaches for targeting this ubiquitous human pathogen are urgently needed. In this review, we describe the strategies that have been successfully applied for the identification of nonconventional antichlamydial agents, including target-based and ligand-based virtual screening, ethnopharmacological approach and pharmacophore-based design of antimicrobial peptide-mimicking compounds. Among the antichlamydial agents identified via these strategies, most translational work has been carried out with plant phenolics. Thus, currently available data on their properties as antichlamydial agents are described, highlighting their potential mechanisms of action. In this context, the role of mitogen-activated protein kinase activation in the intracellular growth and survival of C. pneumoniae is discussed. Owing to the complex and often complementary pathways applied by C. pneumoniae in the different stages of its life cycle, multitargeted therapy approaches are expected to provide better tools for antichlamydial therapy than agents with a single molecular target. MDPI 2016-11-28 /pmc/articles/PMC5192526/ /pubmed/27916800 http://dx.doi.org/10.3390/microorganisms4040043 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Hanski, Leena Vuorela, Pia Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors |
title | Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors |
title_full | Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors |
title_fullStr | Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors |
title_full_unstemmed | Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors |
title_short | Lead Discovery Strategies for Identification of Chlamydia pneumoniae Inhibitors |
title_sort | lead discovery strategies for identification of chlamydia pneumoniae inhibitors |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192526/ https://www.ncbi.nlm.nih.gov/pubmed/27916800 http://dx.doi.org/10.3390/microorganisms4040043 |
work_keys_str_mv | AT hanskileena leaddiscoverystrategiesforidentificationofchlamydiapneumoniaeinhibitors AT vuorelapia leaddiscoverystrategiesforidentificationofchlamydiapneumoniaeinhibitors |