Open Access

Nature Communications, volume 10, issue 1, publication number 524

The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model

Liu Yang ^{1, 2}

Gao Yamin ^{2, 3}

Liu Jianxiong ⁴

Tan Yaoju ⁴

Liu Zhiyong ²

Chhotaray Chiranjibi ^{2, 3}

Jiang Huofeng ^{2, 5}

Lu Zhili ²

Gift Chiwala ^{2, 3}

Wang Shuai ^{2, 3}

Makafe Gaelle ^{2, 3}

Islam Md Mahmudul ^{2, 3}

Hameed H M Adnan ^{2, 3}

Cai Xingshan ⁴

Wang Changwei ²

Li Xinjie ⁴

Tan Shouyong ⁴

Zhang Tianyu ^{2, 3}

Hide authors affiliations Show authors affiliations: 5 affiliations

Institute of Physical Science and Information Technology, Anhui University, Hefei, China |

State Key Laboratory of Respiratory Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China |

University of Chinese Academy of Sciences (UCAS), Beijing, China |

⁴

State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, Guangzhou Chest Hospital, Guangzhou, China |

⁵

School of life Sciences, University of Science and Technology of China, Hefei, China |

Publication type: Journal Article

Publication date: 2019-01-31

Springer Nature

Journal: Nature Communications

Quartile SCImago

Quartile WOS

Impact factor: 16.6

ISSN: 20411723

DOI: 10.1038/s41467-019-08464-y

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PubMed ID: 30705268

General Chemistry

General Biochemistry, Genetics and Molecular Biology

General Physics and Astronomy

Abstract

Buruli ulcer (BU) is an emerging infectious disease that causes disfiguring skin ulcers. The causative agent, Mycobacterium ulcerans, secretes toxin called mycolactone that triggers inflammation and immunopathology. Existing treatments are lengthy and consist of drugs developed for tuberculosis. Here, we report that a pyrazolo[1,5-a]pyridine-3-carboxamide, TB47, is highly bactericidal against M. ulcerans both in vitro and in vivo. In the validated mouse model of BU, TB47 alone reduces M. ulcerans burden in mouse footpads by more than 2.5 log10 CFU compared to the standard BU treatment regimen recommended by the WHO. We show that mutations of ubiquinol-cytochrome C reductase cytochrome subunit B confer resistance to TB47 and the dissimilarity of CydABs from different mycobacteria may account for their differences in susceptibility to TB47. TB47 is highly potent against M. ulcerans and possesses desirable pharmacological attributes and low toxicity that warrant further assessment of this agent for treatment of BU.Combination therapy for Buruli ulcer (BU) is suboptimal. Here, Liu et al. show that the candidate drug TB47 has potent bactericidal activity against Mycobacterium ulcerans in vitro and in a mouse model, which underscores its potential for shortening the course of BU and treating other mycobacterial diseases.

By date By citations

Citations by journals

	1 2 3
Journal of Medicinal Chemistry	Journal of Medicinal Chemistry, 3, 7.32% Journal of Medicinal Chemistry 3 publications, 7.32%
Antimicrobial Agents and Chemotherapy	Antimicrobial Agents and Chemotherapy, 3, 7.32% Antimicrobial Agents and Chemotherapy 3 publications, 7.32%
Pharmaceuticals	Pharmaceuticals, 2, 4.88% Pharmaceuticals 2 publications, 4.88%
Progress in Biophysics and Molecular Biology	Progress in Biophysics and Molecular Biology, 2, 4.88% Progress in Biophysics and Molecular Biology 2 publications, 4.88%
Biosensors and Bioelectronics	Biosensors and Bioelectronics, 2, 4.88% Biosensors and Bioelectronics 2 publications, 4.88%
ACS Infectious Diseases	ACS Infectious Diseases, 2, 4.88% ACS Infectious Diseases 2 publications, 4.88%
Journal of Natural Products	Journal of Natural Products, 2, 4.88% Journal of Natural Products 2 publications, 4.88%
Frontiers in Cellular and Infection Microbiology	Frontiers in Cellular and Infection Microbiology, 1, 2.44% Frontiers in Cellular and Infection Microbiology 1 publication, 2.44%
Frontiers in Chemistry	Frontiers in Chemistry, 1, 2.44% Frontiers in Chemistry 1 publication, 2.44%
Journal of Infection and Public Health	Journal of Infection and Public Health, 1, 2.44% Journal of Infection and Public Health 1 publication, 2.44%
PLoS ONE	PLoS ONE, 1, 2.44% PLoS ONE 1 publication, 2.44%
Cell Chemical Biology	Cell Chemical Biology, 1, 2.44% Cell Chemical Biology 1 publication, 2.44%
Biomedicine and Pharmacotherapy	Biomedicine and Pharmacotherapy, 1, 2.44% Biomedicine and Pharmacotherapy 1 publication, 2.44%
Acta Pharmaceutica Sinica B	Acta Pharmaceutica Sinica B, 1, 2.44% Acta Pharmaceutica Sinica B 1 publication, 2.44%
Journal of Controlled Release	Journal of Controlled Release, 1, 2.44% Journal of Controlled Release 1 publication, 2.44%
Immunological Reviews	Immunological Reviews, 1, 2.44% Immunological Reviews 1 publication, 2.44%
Journal of Organic Chemistry	Journal of Organic Chemistry, 1, 2.44% Journal of Organic Chemistry 1 publication, 2.44%
New Journal of Chemistry	New Journal of Chemistry, 1, 2.44% New Journal of Chemistry 1 publication, 2.44%
Chemical Communications	Chemical Communications, 1, 2.44% Chemical Communications 1 publication, 2.44%
RSC Advances	RSC Advances, 1, 2.44% RSC Advances 1 publication, 2.44%
Expert Review of Clinical Pharmacology	Expert Review of Clinical Pharmacology, 1, 2.44% Expert Review of Clinical Pharmacology 1 publication, 2.44%
Drug Design, Development and Therapy	Drug Design, Development and Therapy, 1, 2.44% Drug Design, Development and Therapy 1 publication, 2.44%
Microbiology spectrum	Microbiology spectrum, 1, 2.44% Microbiology spectrum 1 publication, 2.44%
Proceedings of the National Academy of Sciences of the United States of America	Proceedings of the National Academy of Sciences of the United States of America, 1, 2.44% Proceedings of the National Academy of Sciences of the United States of America 1 publication, 2.44%
eLife	eLife, 1, 2.44% eLife 1 publication, 2.44%
Bioorganic and Medicinal Chemistry Letters	Bioorganic and Medicinal Chemistry Letters, 1, 2.44% Bioorganic and Medicinal Chemistry Letters 1 publication, 2.44%
European Journal of Medicinal Chemistry	European Journal of Medicinal Chemistry, 1, 2.44% European Journal of Medicinal Chemistry 1 publication, 2.44%
Therapeutic Advances in Infectious Disease	Therapeutic Advances in Infectious Disease, 1, 2.44% Therapeutic Advances in Infectious Disease 1 publication, 2.44%
Letters in Drug Design and Discovery	Letters in Drug Design and Discovery, 1, 2.44% Letters in Drug Design and Discovery 1 publication, 2.44%
	1 2 3

Citations by publishers

	2 4 6 8 10 12
Elsevier	Elsevier, 11, 26.83% Elsevier 11 publications, 26.83%
American Chemical Society (ACS)	American Chemical Society (ACS), 8, 19.51% American Chemical Society (ACS) 8 publications, 19.51%
American Society for Microbiology	American Society for Microbiology, 4, 9.76% American Society for Microbiology 4 publications, 9.76%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 3, 7.32% Royal Society of Chemistry (RSC) 3 publications, 7.32%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 2, 4.88% Multidisciplinary Digital Publishing Institute (MDPI) 2 publications, 4.88%
Frontiers Media S.A.	Frontiers Media S.A., 2, 4.88% Frontiers Media S.A. 2 publications, 4.88%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 2, 4.88% Cold Spring Harbor Laboratory 2 publications, 4.88%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 1, 2.44% Public Library of Science (PLoS) 1 publication, 2.44%
Wiley	Wiley, 1, 2.44% Wiley 1 publication, 2.44%
Taylor & Francis	Taylor & Francis, 1, 2.44% Taylor & Francis 1 publication, 2.44%
Dove Medical Press	Dove Medical Press, 1, 2.44% Dove Medical Press 1 publication, 2.44%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 1, 2.44% Proceedings of the National Academy of Sciences (PNAS) 1 publication, 2.44%
eLife Sciences Publications	eLife Sciences Publications, 1, 2.44% eLife Sciences Publications 1 publication, 2.44%
SAGE	SAGE, 1, 2.44% SAGE 1 publication, 2.44%
Bentham Science	Bentham Science, 1, 2.44% Bentham Science 1 publication, 2.44%
	2 4 6 8 10 12

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GOST Copy

Liu Y. et al. The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model // Nature Communications. 2019. Vol. 10. No. 1. 524

GOST all authors (up to 50) Copy

Liu Y., Gao Y., Liu J., Tan Y., Liu Z., Chhotaray C., Jiang H., Lu Z., Gift C., Wang S., Makafe G., Islam M. M., Hameed H. M. A., Cai X., Wang C., Li X., Tan S., Zhang T. The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model // Nature Communications. 2019. Vol. 10. No. 1. 524

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/s41467-019-08464-y

UR - https://doi.org/10.1038%2Fs41467-019-08464-y

TI - The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model

T2 - Nature Communications

AU - Liu, Yang

AU - Gao, Yamin

AU - Liu, Jianxiong

AU - Tan, Yaoju

AU - Liu, Zhiyong

AU - Chhotaray, Chiranjibi

AU - Jiang, Huofeng

AU - Lu, Zhili

AU - Gift, Chiwala

AU - Wang, Shuai

AU - Makafe, Gaelle

AU - Islam, Md Mahmudul

AU - Hameed, H M Adnan

AU - Cai, Xingshan

AU - Wang, Changwei

AU - Li, Xinjie

AU - Tan, Shouyong

AU - Zhang, Tianyu

PY - 2019

DA - 2019/01/31 00:00:00

PB - Springer Nature

IS - 1

VL - 10

PMID - 30705268

SN - 2041-1723

ER -

BibTex

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BibTex Copy

@article{2019_Liu,

author = {Yang Liu and Yamin Gao and Jianxiong Liu and Yaoju Tan and Zhiyong Liu and Chiranjibi Chhotaray and Huofeng Jiang and Zhili Lu and Chiwala Gift and Shuai Wang and Gaelle Makafe and Md Mahmudul Islam and H M Adnan Hameed and Xingshan Cai and Changwei Wang and Xinjie Li and Shouyong Tan and Tianyu Zhang},

title = {The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model},

journal = {Nature Communications},

year = {2019},

volume = {10},

publisher = {Springer Nature},

month = {jan},

url = {https://doi.org/10.1038%2Fs41467-019-08464-y},

number = {1},

doi = {10.1038/s41467-019-08464-y}

}

Found error?

Publisher

Springer Nature

Journal

Nature Communications

Quartile SCImago

Quartile WOS

Impact factor

16.6

ISSN

20411723 (Print)