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GrgA as a potential target of selective antichlamydials

Chlamydia is a common pathogen that can causes serious complications in the reproductive system and eyes. Lack of vaccine and other effective prophylactic measures coupled with the largely asymptomatic nature and unrare clinical treatment failure calls for development of new antichlamydials, particu...

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Autores principales: Zhang, Huirong, Vellappan, Sangeevan, Tang, M. Matt, Bao, Xiaofeng, Fan, Huizhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396966/
https://www.ncbi.nlm.nih.gov/pubmed/30822328
http://dx.doi.org/10.1371/journal.pone.0212874
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author Zhang, Huirong
Vellappan, Sangeevan
Tang, M. Matt
Bao, Xiaofeng
Fan, Huizhou
author_facet Zhang, Huirong
Vellappan, Sangeevan
Tang, M. Matt
Bao, Xiaofeng
Fan, Huizhou
author_sort Zhang, Huirong
collection PubMed
description Chlamydia is a common pathogen that can causes serious complications in the reproductive system and eyes. Lack of vaccine and other effective prophylactic measures coupled with the largely asymptomatic nature and unrare clinical treatment failure calls for development of new antichlamydials, particularly selective antichlamydials without adverse effects on humans and the beneficial microbiota. We previously reported that benzal-N-acylhydrazones (BAH) can inhibit chlamydiae without detectable adverse effects on host cells and beneficial lactobacilli that dominate the human vaginal microbiota among reproductive-age women. However, the antichlamydial mechanism of BAH is not known. Whereas 4 single nucleotide polymorphisms (i.e., SNP1-4) were identified in a rare Chlamydia variant with a low level of BAH resistance, termed MCR, previous studies failed to establish a causal effect of any particular SNP(s). In the present work, we performed recombination to segregate the four SNPs. Susceptibility tests indicate that the R51G GrgA allele is both necessary and sufficient for the low level of BAH resistance. Thus, the Chlamydia-specific transcription factor GrgA either is a direct target of BAH or regulates BAH susceptibility. We further confirm an extremely low rate of BAH resistance in Chlamydia. Our findings warrant exploration of GrgA as a therapeutic and prophylactic target for chlamydial infections.
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spelling pubmed-63969662019-03-08 GrgA as a potential target of selective antichlamydials Zhang, Huirong Vellappan, Sangeevan Tang, M. Matt Bao, Xiaofeng Fan, Huizhou PLoS One Research Article Chlamydia is a common pathogen that can causes serious complications in the reproductive system and eyes. Lack of vaccine and other effective prophylactic measures coupled with the largely asymptomatic nature and unrare clinical treatment failure calls for development of new antichlamydials, particularly selective antichlamydials without adverse effects on humans and the beneficial microbiota. We previously reported that benzal-N-acylhydrazones (BAH) can inhibit chlamydiae without detectable adverse effects on host cells and beneficial lactobacilli that dominate the human vaginal microbiota among reproductive-age women. However, the antichlamydial mechanism of BAH is not known. Whereas 4 single nucleotide polymorphisms (i.e., SNP1-4) were identified in a rare Chlamydia variant with a low level of BAH resistance, termed MCR, previous studies failed to establish a causal effect of any particular SNP(s). In the present work, we performed recombination to segregate the four SNPs. Susceptibility tests indicate that the R51G GrgA allele is both necessary and sufficient for the low level of BAH resistance. Thus, the Chlamydia-specific transcription factor GrgA either is a direct target of BAH or regulates BAH susceptibility. We further confirm an extremely low rate of BAH resistance in Chlamydia. Our findings warrant exploration of GrgA as a therapeutic and prophylactic target for chlamydial infections. Public Library of Science 2019-03-01 /pmc/articles/PMC6396966/ /pubmed/30822328 http://dx.doi.org/10.1371/journal.pone.0212874 Text en © 2019 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Huirong
Vellappan, Sangeevan
Tang, M. Matt
Bao, Xiaofeng
Fan, Huizhou
GrgA as a potential target of selective antichlamydials
title GrgA as a potential target of selective antichlamydials
title_full GrgA as a potential target of selective antichlamydials
title_fullStr GrgA as a potential target of selective antichlamydials
title_full_unstemmed GrgA as a potential target of selective antichlamydials
title_short GrgA as a potential target of selective antichlamydials
title_sort grga as a potential target of selective antichlamydials
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396966/
https://www.ncbi.nlm.nih.gov/pubmed/30822328
http://dx.doi.org/10.1371/journal.pone.0212874
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