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An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE
by
Chen, Po-Pang
, Song, Pin-Yi
, Chen, Yung-Chih
, Tsai, Chia-En
, Hu, Chao-Yuan
, Wang, Tzu-Haw
, Huang, Yu-Wen
, Chen, Po-Yin
, Ku, Chuan
, Hsia, Kuo-Chiang
, Ting, See-Yeun
in
ABC transporters
/ Adenosine triphosphatase
/ Bacteria
/ Bacterial toxins
/ Bacterial Toxins - metabolism
/ Biology and Life Sciences
/ Cell development (Biology)
/ Cell growth
/ Chromosome Segregation - drug effects
/ Competition
/ Cysteine
/ Cysteine Proteases - metabolism
/ Cysteine proteinase
/ Cysteine proteinases
/ Deoxyribonucleic acid
/ DNA
/ DNA biosynthesis
/ DNA Gyrase - chemistry
/ DNA Gyrase - metabolism
/ DNA replication
/ DNA Replication - drug effects
/ DNA topoisomerase
/ DNA Topoisomerase IV - chemistry
/ DNA Topoisomerase IV - metabolism
/ E coli
/ Escherichia coli
/ Escherichia coli - enzymology
/ Escherichia coli - genetics
/ Escherichia coli - growth & development
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - chemistry
/ Escherichia coli Proteins - metabolism
/ Gram-negative bacteria
/ Gram-positive bacteria
/ Growth
/ Immunity
/ Intoxication
/ Medicine and Health Sciences
/ Microbial activity
/ Microbiological research
/ Microorganisms
/ Neutralization
/ Nucleotide sequence
/ Occlusion
/ Papain
/ Peptides
/ Phylogenetics
/ Physiological aspects
/ Protease
/ Proteases
/ Proteins
/ Proteolysis
/ Research and Analysis Methods
/ Topoisomerases
/ Toxicity
/ Toxins
2025
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An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE
by
Chen, Po-Pang
, Song, Pin-Yi
, Chen, Yung-Chih
, Tsai, Chia-En
, Hu, Chao-Yuan
, Wang, Tzu-Haw
, Huang, Yu-Wen
, Chen, Po-Yin
, Ku, Chuan
, Hsia, Kuo-Chiang
, Ting, See-Yeun
in
ABC transporters
/ Adenosine triphosphatase
/ Bacteria
/ Bacterial toxins
/ Bacterial Toxins - metabolism
/ Biology and Life Sciences
/ Cell development (Biology)
/ Cell growth
/ Chromosome Segregation - drug effects
/ Competition
/ Cysteine
/ Cysteine Proteases - metabolism
/ Cysteine proteinase
/ Cysteine proteinases
/ Deoxyribonucleic acid
/ DNA
/ DNA biosynthesis
/ DNA Gyrase - chemistry
/ DNA Gyrase - metabolism
/ DNA replication
/ DNA Replication - drug effects
/ DNA topoisomerase
/ DNA Topoisomerase IV - chemistry
/ DNA Topoisomerase IV - metabolism
/ E coli
/ Escherichia coli
/ Escherichia coli - enzymology
/ Escherichia coli - genetics
/ Escherichia coli - growth & development
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - chemistry
/ Escherichia coli Proteins - metabolism
/ Gram-negative bacteria
/ Gram-positive bacteria
/ Growth
/ Immunity
/ Intoxication
/ Medicine and Health Sciences
/ Microbial activity
/ Microbiological research
/ Microorganisms
/ Neutralization
/ Nucleotide sequence
/ Occlusion
/ Papain
/ Peptides
/ Phylogenetics
/ Physiological aspects
/ Protease
/ Proteases
/ Proteins
/ Proteolysis
/ Research and Analysis Methods
/ Topoisomerases
/ Toxicity
/ Toxins
2025
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An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE
by
Chen, Po-Pang
, Song, Pin-Yi
, Chen, Yung-Chih
, Tsai, Chia-En
, Hu, Chao-Yuan
, Wang, Tzu-Haw
, Huang, Yu-Wen
, Chen, Po-Yin
, Ku, Chuan
, Hsia, Kuo-Chiang
, Ting, See-Yeun
in
ABC transporters
/ Adenosine triphosphatase
/ Bacteria
/ Bacterial toxins
/ Bacterial Toxins - metabolism
/ Biology and Life Sciences
/ Cell development (Biology)
/ Cell growth
/ Chromosome Segregation - drug effects
/ Competition
/ Cysteine
/ Cysteine Proteases - metabolism
/ Cysteine proteinase
/ Cysteine proteinases
/ Deoxyribonucleic acid
/ DNA
/ DNA biosynthesis
/ DNA Gyrase - chemistry
/ DNA Gyrase - metabolism
/ DNA replication
/ DNA Replication - drug effects
/ DNA topoisomerase
/ DNA Topoisomerase IV - chemistry
/ DNA Topoisomerase IV - metabolism
/ E coli
/ Escherichia coli
/ Escherichia coli - enzymology
/ Escherichia coli - genetics
/ Escherichia coli - growth & development
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - chemistry
/ Escherichia coli Proteins - metabolism
/ Gram-negative bacteria
/ Gram-positive bacteria
/ Growth
/ Immunity
/ Intoxication
/ Medicine and Health Sciences
/ Microbial activity
/ Microbiological research
/ Microorganisms
/ Neutralization
/ Nucleotide sequence
/ Occlusion
/ Papain
/ Peptides
/ Phylogenetics
/ Physiological aspects
/ Protease
/ Proteases
/ Proteins
/ Proteolysis
/ Research and Analysis Methods
/ Topoisomerases
/ Toxicity
/ Toxins
2025
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An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE
Journal Article
An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE
2025
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Overview
Bacteria deploy a diverse arsenal of toxic effectors to antagonize competitors, profoundly influencing the composition of microbial communities. Previous studies have identified an interbacterial toxin predicted to exhibit proteolytic activity that is broadly distributed among gram-negative bacteria. However, the precise mechanism of intoxication remains unresolved. Here, we demonstrate that one such protease toxin from Escherichia coli , Cpe1, disrupts DNA replication and chromosome segregation by cleaving conserved sequences within the ATPase domain of type II DNA topoisomerases GyrB and ParE. This cleavage effectively inhibits topoisomerase-mediated relaxation of supercoiled DNA, resulting in impaired bacterial growth. Cpe1 belongs to the papain-like cysteine protease family and is associated with toxin delivery pathways, including the type VI secretion system and contact-dependent growth inhibition. The structure of Cpe1 in complex with its immunity protein reveals a neutralization mechanism involving competitive substrate binding rather than active site occlusion, distinguishing it from previously characterized effector-immunity pairs. Our findings unveil a unique mode of interbacterial intoxication and provide insights into how bacteria protect themselves from self-poisoning by protease toxins.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Bacteria
/ Bacterial Toxins - metabolism
/ Chromosome Segregation - drug effects
/ Cysteine
/ Cysteine Proteases - metabolism
/ DNA
/ DNA Replication - drug effects
/ DNA Topoisomerase IV - chemistry
/ DNA Topoisomerase IV - metabolism
/ E coli
/ Escherichia coli - enzymology
/ Escherichia coli - growth & development
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - chemistry
/ Escherichia coli Proteins - metabolism
/ Growth
/ Immunity
/ Medicine and Health Sciences
/ Papain
/ Peptides
/ Protease
/ Proteins
/ Research and Analysis Methods
/ Toxicity
/ Toxins
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