Evidence map›Paper›PMID 41124267›Full record

ArticleScience advances2025

Chemically tailored anionic antibiotic adjuvants targeting divalent cations to overcome carbapenem resistance in gram-negative bacteria.

Hao Tang, Xiaomeng Zhao, Mengsi Sun, Jie Qi, Zhihao Huang, Yihang Zhu, Yingmin Zeng, Yong Xia, Zhi Luo, Xingyu Jiang

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Synergistic eradication of NDM-1Materials today. Bio · 2026
    Article
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

10 authors.

Hao TangGuangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China.ORCID 0000-0002-5009-6165
Xiaomeng ZhaoGuangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China.ORCID 0009-0005-0476-8775
Mengsi SunInstitute of Chemical Biology, Shenzhen Bay Laboratory, Guangming District, Shenzhen, Guangdong 518055, P. R. China.ORCID 0009-0006-7915-4281
Jie QiGuangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China.ORCID 0000-0001-9636-755X
Zhihao HuangGuangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China.ORCID 0009-0000-3020-4790
Yihang ZhuGuangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China.ORCID 0009-0002-5395-7992
Yingmin ZengDepartment of Clinical Laboratory, Third Affiliated Hospital of Guangzhou Medical University, No. 63 Duobao Road, Liwan District, Guangzhou, Guangdong 510150, P. R. China.
Yong XiaDepartment of Clinical Laboratory, Third Affiliated Hospital of Guangzhou Medical University, No. 63 Duobao Road, Liwan District, Guangzhou, Guangdong 510150, P. R. China.
Zhi LuoGuangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China.ORCID 0000-0001-5590-4849
Xingyu JiangGuangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, P. R. China.ORCID 0000-0002-5008-4703

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

No clinically available antibiotic adjuvants can overcome metallo-β-lactamase (MBL) resistance in carbapenem-resistant Gram-negative ESKAPE pathogens. Divalent cations in MBL and quasicrystalline lipopolysaccharides (LPS) are key determinants of acquired and intrinsic resistance in these bacteria. Chemically depriving these cations would block multiple resistance pathways simultaneously and restore carbapenem susceptibility. Here, we chemically engineer a class of anionic adjuvants to tailor their interactions with MBL, enhancing the enzymatic inhibition by up to ~5885-fold compared to parent compounds. An orthogonal screen identifies the tiopronin-engineered anionic adjuvant (TINA), which achieves complete rescue of all tested carbapenems against diverse New Delhi metallo-β-lactamase-1-producing Gram-negative ESKAPE bacteria. TINA targets both MBL and LPS, depriving divalent cations to inactivate MBL and damage membrane collaboratively while also preventing resistance evolution. Moreover, TINA's anionic nature minimizes serum adsorption, enabling safe and effective in vivo treatment of bacterial pneumonia. This work provides an innovative chemical biology strategy leveraging anionic materials to combat superbugs globally.

Indexed as

Anti-Bacterial AgentsCarbapenemsCations, DivalentDrug Resistance, BacterialGram-Negative BacteriaAnimalsAnionsbeta-LactamasesHumansMiceMicrobial Sensitivity TestsAnionsAnti-Bacterial Agentsbeta-LactamasesCarbapenemsCations, Divalent

Identifiers

PMID41124267
PMCPMC12542962

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.