Evidence map›Paper›PMID 40804467›Full record

ArticleCommunications biology2025

Mutations in ClpC1 or ClpX subunit of caseinolytic protease confer resistance to ilamycins in mycobacteria.

Yamin Gao, Cuiting Fang, Biao Zhou, H M Adnan Hameed, Changli Sun, Xirong Tian, Jing He, Xingli Han, Han Zhang, Jun Li and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Yamin Gao *State Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Cuiting Fang *State Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Biao ZhouState Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
H M Adnan HameedState Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Changli SunUniversity of Chinese Academy of Sciences, Beijing, China.
Xirong TianState Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Jing HeState Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Xingli HanState Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Han ZhangState Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Jun LiShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Jianhua JuUniversity of Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0001-7712-8027
Xinwen ChenGuangzhou National Laboratory, Guangzhou, China.
Nanshan ZhongGuangzhou National Laboratory, Guangzhou, China.
Junying MaUniversity of Chinese Academy of Sciences, Beijing, China. majunying@scsio.ac.cn.ORCID http://orcid.org/0000-0002-0641-7291
Xiaoli XiongState Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. xiong_xiaoli@gibh.ac.cn.ORCID http://orcid.org/0000-0002-4632-9122
Tianyu ZhangState Key Laboratory of Respiratory Disease, Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. zhang_tianyu@gibh.ac.cn.ORCID http://orcid.org/0000-0001-5647-6014

Funding

China Postdoctoral Science Foundation 2022M723164Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2021YFA1300900National Natural Science Foundation of China (National Science Foundation of China) 32300152National Natural Science Foundation of China (National Science Foundation of China) 81973372State Key Laboratory of Respiratory Disease (SKLRD) SKLRD-Z-202301State Key Laboratory of Respiratory Disease (SKLRD) SKLRD-Z-202414
6 · The paper itself

Abstract

The mycobacterial caseinolytic protease (Clp) system has been recognized as a promising therapeutic target. In this study, we identify two novel ilamycin analogs, ilamycin E (ILE) and ilamycin F (ILF), both targeting the ClpC1 component of the ClpC1P1P2 proteasome. ILE potently disrupts ClpC1P1P2-mediated proteolysis, leading to delayed bactericidal activity, while ILF also binds ClpC1, albeit with lower affinity. Notably, we discover and validate a unique mutation in clpX and a novel insertion in clpC1 both conferring resistance to ILE and ILF in mycobacterium by gene editing. Furthermore, ILE can also inhibit the proteolytic activity of ClpXP1P2 in a manner dependent on the substrate's tag sequence and adaptor. This first demonstration of clpX- and clpC1-mediated ilamycins resistance underscores the potential of ilamycins to target multiple components of the Clp protease system, offering a novel dual-target strategy for combating mycobacterial infections.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsDrug Resistance, BacterialEndopeptidase ClpMutationMycobacteriumHeat-Shock ProteinsProteolysisAnti-Bacterial AgentsBacterial ProteinsClpC1 protein, Mycobacterium tuberculosisEndopeptidase ClpHeat-Shock Proteins

Identifiers

PMID40804467
PMCPMC12350849

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.