Evidence map›Paper›PMID 35674439›Full record

ArticleMicrobiology spectrum2022

Crizotinib Shows Antibacterial Activity against Gram-Positive Bacteria by Reducing ATP Production and Targeting the CTP Synthase PyrG.

Yun-Dan Zheng, Tairan Zhong, Haiming Wu, Nan Li, Zuye Fang, Linlin Cao, Xing-Feng Yin, Qing-Yu He, Ruiguang Ge, Xuesong Sun

Open access · goldAbstract read
In one paragraph

Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
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

13 citing papers in PubMed, 20 citations in OpenAlex.

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  13. Endodontic potential of eugenol againstJournal of oral biology and craniofacial research
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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 at 2 institutions in 1 country.

Yun-Dan ZhengMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.
Tairan ZhongMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.
Haiming WuMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.
Nan LiMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.
Zuye FangMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.
Linlin CaoMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.
Xing-Feng YinMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.
Qing-Yu HeMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.
Ruiguang GeState Key Laboratory of Biocontrol, College of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
Xuesong SunMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan Universitygrid.258164.c, Guangzhou, China.ORCID 0000-0002-5425-321X
Jinan University · CNSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Infections caused by drug-resistant bacteria are a serious threat to public health worldwide, and the discovery of novel antibacterial compounds is urgently needed. Here, we screened an FDA-approved small-molecule library and found that crizotinib possesses good antimicrobial efficacy against Gram-positive bacteria. Crizotinib was found to increase the survival rate of mice infected with bacteria and decrease pulmonary inflammation activity in an animal model. Furthermore, it showed synergy with clindamycin and gentamicin. Importantly, the Gram-positive bacteria showed a low tendency to develop resistance to crizotinib. Mechanistically, quantitative proteomics and biochemical validation experiments indicated that crizotinib exerted its antibacterial effects by reducing ATP production and pyrimidine metabolism. A drug affinity responsive target stability study suggested crizotinib targets the CTP synthase PyrG, which subsequently disturbs pyrimidine metabolism and eventually reduces DNA synthesis. Subsequent molecular dynamics analysis showed that crizotinib binding occurs in close proximity to the ATP binding pocket of PyrG and causes loss of function of this CTP synthase. Crizotinib is a promising antimicrobial agent and provides a novel choice for the development of treatment for Gram-positive infections.

Indexed as

Anti-Bacterial AgentsGram-Positive BacteriaAdenosine TriphosphateAnimalsBacteriaCarbon-Nitrogen LigasesCrizotinibDNAGram-Negative BacteriaMiceMicrobial Sensitivity TestsPyrimidinesAdenosine TriphosphateAnti-Bacterial AgentsCarbon-Nitrogen LigasesCrizotinibCTP synthetaseDNAPyrimidinescrizotinibdrug repurposingGram-positive bacteriaquantitative proteomics

Identifiers

PMID35674439
PMCPMC9241945
OpenAlexW4282943119

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.