Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages.
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. Thus, identification of new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to reduce the side effects of anti-TB drugs, such as l...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2019-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0199799 |
id |
doaj-d8945ba21d624717bc656d3c530d89b8 |
---|---|
record_format |
Article |
spelling |
doaj-d8945ba21d624717bc656d3c530d89b82021-03-03T20:49:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e019979910.1371/journal.pone.0199799Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages.Hyo-Ji LeeHyun-Jeong KoSeung Hyun KimYu-Jin JungTuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. Thus, identification of new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to reduce the side effects of anti-TB drugs, such as liver toxicity and other detrimental changes, is urgently needed. In this study, to develop a novel candidate drug for effective TB treatment with few side effects in the host, we selected pasakbumin A isolated from Eurycoma longifolia (E. longifolia) Jack, which protected host cells against Mtb infection-induced death. Pasakbumin A significantly inhibited intracellular Mtb growth by inducing the autophagy via the ERK1/2-mediated signaling pathway in Mtb-infected macrophages. We further investigated whether pasakbumin A could be used as a potential adjuvant for TB treatment. Treatment with pasakbumin A and anti-TB drug rifampicin (RMP) potently suppressed intracellular Mtb killing by promoting autophagy as well as TNF-α production via the ERK1/2- and NF-κB-mediated signaling pathways in Mtb-infected cells. Our results suggest that pasakbumin A could be developed as a novel anti-TB drug or host-directed therapeutic (HDT) strategy to protect against host cell death and improve host defense mechanisms against Mtb infection in macrophages.https://doi.org/10.1371/journal.pone.0199799 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hyo-Ji Lee Hyun-Jeong Ko Seung Hyun Kim Yu-Jin Jung |
spellingShingle |
Hyo-Ji Lee Hyun-Jeong Ko Seung Hyun Kim Yu-Jin Jung Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. PLoS ONE |
author_facet |
Hyo-Ji Lee Hyun-Jeong Ko Seung Hyun Kim Yu-Jin Jung |
author_sort |
Hyo-Ji Lee |
title |
Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. |
title_short |
Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. |
title_full |
Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. |
title_fullStr |
Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. |
title_full_unstemmed |
Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. |
title_sort |
pasakbumin a controls the growth of mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. Thus, identification of new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to reduce the side effects of anti-TB drugs, such as liver toxicity and other detrimental changes, is urgently needed. In this study, to develop a novel candidate drug for effective TB treatment with few side effects in the host, we selected pasakbumin A isolated from Eurycoma longifolia (E. longifolia) Jack, which protected host cells against Mtb infection-induced death. Pasakbumin A significantly inhibited intracellular Mtb growth by inducing the autophagy via the ERK1/2-mediated signaling pathway in Mtb-infected macrophages. We further investigated whether pasakbumin A could be used as a potential adjuvant for TB treatment. Treatment with pasakbumin A and anti-TB drug rifampicin (RMP) potently suppressed intracellular Mtb killing by promoting autophagy as well as TNF-α production via the ERK1/2- and NF-κB-mediated signaling pathways in Mtb-infected cells. Our results suggest that pasakbumin A could be developed as a novel anti-TB drug or host-directed therapeutic (HDT) strategy to protect against host cell death and improve host defense mechanisms against Mtb infection in macrophages. |
url |
https://doi.org/10.1371/journal.pone.0199799 |
work_keys_str_mv |
AT hyojilee pasakbuminacontrolsthegrowthofmycobacteriumtuberculosisbyenhancingtheautophagyandproductionofantibacterialmediatorsinmousemacrophages AT hyunjeongko pasakbuminacontrolsthegrowthofmycobacteriumtuberculosisbyenhancingtheautophagyandproductionofantibacterialmediatorsinmousemacrophages AT seunghyunkim pasakbuminacontrolsthegrowthofmycobacteriumtuberculosisbyenhancingtheautophagyandproductionofantibacterialmediatorsinmousemacrophages AT yujinjung pasakbuminacontrolsthegrowthofmycobacteriumtuberculosisbyenhancingtheautophagyandproductionofantibacterialmediatorsinmousemacrophages |
_version_ |
1714820424500510720 |