EmbB and EmbC regulate the sensitivity of Mycobacterium abscessus to echinomycin

作     者：Jing He Yamin Gao Jingyun Wang H.M.Adnan Hameed Shuai Wang Cuiting Fang Xirong Tian Jingran Zhang Xingli Han Yanan Ju Yaoju Tan Junying Ma Jianhua Ju Jinxing Hu Jianxion Liu Tianyu Zhang 

作者机构：Institute of Physical Science and Information TechnologyAnhui UniversityHefeiChina State Key Laboratory of Respiratory DiseaseGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious DiseasesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina China-New Zealand Joint Laboratory on Biomedicine and HealthGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina University of Chinese Academy of SciencesBejingChina School of PharmacyInstitute of Marine DrugGuangxi University of Traditional Chinese MedicineNanningChina CAS Key Laboratory of Tropical Marine Bio-Resources and EcologyRNAM Center for Marine MicrobiologyGuangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhouChina School of Life SciencesUniversity of Science and Technology of ChinaHefeiChina State Key Laboratory of Respiratory DiseaseGuangzhou Chest HospitalGuangzhouChina 

出 版 物：《mLife》 (微生物（英文）)

年 卷 期：2024年第3卷第3期

页      面：459-470页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 07[理学] 071005[理学-微生物学] 10[医学] 

基　　金：This work was supported by the National Key R&D Program of China(2021YFA1300900) the National Natural Science Foundation of China(21920102003,82022067,and 22037006) the Chinese Academy of Sciences Grants(154144KYSB20190005 and YJKYYQ20210026) the Key R&D Program of Sichuan Provenience(2023YFSY0047) the State Key Laboratory of Respiratory Disease,Guangzhou Institute of Respiratory Diseases,First Affiliated Hospital of Guangzhou Medical University(SKLRD-Z-202414,SKLRD-OP-202324,SKLRD-Z-202301,SKLRD-OP-202113,and SKLRD-Z-202412) Guangzhou Scienceaand Technology Plan-Youth Doctoral"Sail"Project(2024A04J4273) President's International Fellowship Initiative-CAS(2023VBC0015) the National Foreign Young Talent Program(QN2022031002L) 

主　　题：echinomycin EmbB EmbC functional compensation Mycobacterium abscessus 

摘      要：Treatment of Mycobacterium abscessus(Mab)infections is very challenging due to its intrinsic resistance to most available ***,it is crucial to discover novel anti-Mab *** this study,we explored an intrinsic resistance mechanism through which Mab resists echinomycin(ECH).ECH showed activity against Mab at a minimum inhibitory concentration(MIC)of 2μg/ml.A embC strain in which the embC gene was knocked out showed hypersensitivity to ECH(MIC:0.0078-0.0156μg/ml).The MICs of ECH-resistant strains screened with reference to AembC ranged from 0.25 to 1μg/*** in EmbB,including D306A,D306N,R350G,V555l,and G581S,increased the Mab s resistance to ECH when overexpressed in AembC individually(MIC:0.25-0.5μg/ml).These EmbB mutants,edited using the CRISPR/Cpf1 system,showed heightened resistance to ECH(MIC:0.25-0.5μg/ml).The permeability of these Mab strains with edited genes and overexpression was reduced,as evidenced by an ethidium bromide accumulation assay,but it remained significantly higher than that of the parent *** summary,our study demonstrates that ECH exerts potent anti-Mab activity and confirms that EmbB and EmbC are implicated in Mab s sensitivity to *** in EmbB may partially compensate foralossof EmbCfunction.