Jing He: Institute of Physical Science and Information Technology Anhui University Hefei China. ORCID
Yamin Gao: State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China.
Jingyun Wang: School of Pharmacy, Institute of Marine Drug Guangxi University of Traditional Chinese Medicine Nanning China.
H M Adnan Hameed: State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China. ORCID
Shuai Wang: State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China.
Cuiting Fang: State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China.
Xirong Tian: State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China.
Jingran Zhang: State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China.
Xingli Han: State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China.
Yanan Ju: State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China.
Yaoju Tan: State Key Laboratory of Respiratory Disease Guangzhou Chest Hospital Guangzhou China.
Junying Ma: CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences Guangzhou China.
Jianhua Ju: CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences Guangzhou China.
Jinxing Hu: State Key Laboratory of Respiratory Disease Guangzhou Chest Hospital Guangzhou China.
Jianxiong Liu: State Key Laboratory of Respiratory Disease Guangzhou Chest Hospital Guangzhou China.
Tianyu Zhang: Institute of Physical Science and Information Technology Anhui University Hefei China. ORCID
Treatment of (Mab) infections is very challenging due to its intrinsic resistance to most available drugs. Therefore, it is crucial to discover novel anti-Mab drugs. In 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 2�����g/ml. A ��embC strain in which the gene was knocked out showed hypersensitivity to ECH (MIC: 0.0078-0.0156�����g/ml). The MICs of ECH-resistant strains screened with reference to ��embC ranged from 0.25 to 1�����g/ml. Mutations in EmbB, including D306A, D306N, R350G, V555I, and G581S, increased the Mab's resistance to ECH when overexpressed in ��embC individually (MIC: 0.25-0.5�����g/ml). These EmbB mutants, edited using the CRISPR/Cpf1 system, showed heightened resistance to ECH (MIC: 0.25-0.5�����g/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 Mab. In summary, our study demonstrates that ECH exerts potent anti-Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH. Mutation in EmbB may partially compensate for a loss of EmbC function.
