A preliminary study on the regulation and analysis of indole mediated bidirectional chemotaxis behavior of <italic style="font-style: italic">Escherichia coli</italic>

WANG Kunkun; CHEN Hongyu; ZHANG Andong; LU Xiaoyun; TAN Dan

doi:10.12211/2096-8280.2025-036

您当前的位置：

首页 >

文章列表页 >

A preliminary study on the regulation and analysis of indole mediated bidirectional chemotaxis behavior of Escherichia coli

Research Article | 更新时间：2026-01-15

- A preliminary study on the regulation and analysis of indole mediated bidirectional chemotaxis behavior of Escherichia coli
- Synthetic Biology Journal Vol. 6, Issue 6, Pages: 1398-1420(2025)
- 作者机构：
  
  1.西安交通大学生命科学与技术学院，生物医学信息工程教育部重点实验室，陕西西安 710049
  2.清华大学生命科学学院，北京 100084
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-036
  CLC： Q819
- Received：29 April 2025，
  
  Revised：2025-07-31，
  
  Published：31 December 2025
- 稿件说明：
移动端阅览
汪昆昆，陈泓宇，张安栋，卢晓云，谭丹. 大肠杆菌中吲哚介导的双向趋化行为的调控与分析［J］. 合成生物学， 2025， 6（6）： 1398-1420

WANG Kunkun， CHEN Hongyu， ZHANG Andong， LU Xiaoyun， TAN Dan. A preliminary study on the regulation and analysis of indole mediated bidirectional chemotaxis behavior of Escherichia coli［J］. Synthetic Biology Journal， 2025， 6（6）： 1398-1420
汪昆昆，陈泓宇，张安栋，卢晓云，谭丹. 大肠杆菌中吲哚介导的双向趋化行为的调控与分析［J］. 合成生物学， 2025， 6（6）： 1398-1420 DOI： 10.12211/2096-8280.2025-036.

WANG Kunkun， CHEN Hongyu， ZHANG Andong， LU Xiaoyun， TAN Dan. A preliminary study on the regulation and analysis of indole mediated bidirectional chemotaxis behavior of Escherichia coli［J］. Synthetic Biology Journal， 2025， 6（6）： 1398-1420 DOI： 10.12211/2096-8280.2025-036.

摘要

细菌趋化性在肠道菌群定植和癌症诊疗等领域发挥着重要作用，也是定量生物学与合成生物学的研究方向之一。大肠杆菌中吲哚诱导的趋化反应主要由两种效应相反的甲基化趋化受体Tsr与Tar介导，两者的拮抗效应可导致双向趋化反应的发生。本文从数学模型的建立与仿真以及实验调控与观测两方面对该双向趋化反应进行研究。基于信号转导动力学与马尔可夫随机游走模型，分别从个体水平和群体水平构建了大肠杆菌在双受体介导下趋化性的数学模型，并对不同受体比例下大肠杆菌的趋化响应行为进行了模拟和仿真分析。同时，利用CRISPRi技术对Tar受体进行了不同程度的可诱导敲低（分别敲低0%、40%和70%），并借助于Transwell细菌迁移实验和自主设计优化的微流控观测平台，对吲哚介导下不同Tar表达量菌株的趋化性行为进行了观测与分析。通过两种甲基化趋化受体Tsr/Tar相对比例的调节实现了细菌趋化行为的调控，同时结合数学建模初步揭示了相互拮抗的两种趋化性受体比例对细菌个体和群体趋化运动的影响，为扩展趋化行为的定量研究和精确调控手段，以及未来细菌趋化性在肠道菌群人工调节等多领域的应用奠定基础。

Abstract

Chemotaxis constitutes a fundamental mechanism underlying bacterial behaviors such as microbiota colonization and cancer therapy

while also representing an actively studied area within quantitative and synthetic biology. The indole induced bidirectional chemotaxis in

Escherichia coli

is mainly mediated by two methylation chemoreceptors (MCPs) with antagonistic effects

Tsr and Tar respectively

which was investigated in this study by mathematical model and experimental verification. Based on signal transduction dynamics model and Markov random walk model

the bidire

ctional chemotaxis of

E. coli

was described and simulated at both individual and population levels. Meanwhile

one of the MCPs receptors Tar was knockdown by 0%

40% and 70% respectively

via

CRISPRi

and the chemotaxis behaviors of knockdown strains with different Tar expression levels under indole induction were observed and analyzed by Transwell migration experiment and self-designed microfluidics platform. The regulation of bacterial chemotaxis behavior was achieved in this study by adjusting the ratio of two antagonistic chemotaxis receptors Tsr and Tar

and together with mathematical model and experimental observation

the influence of Tsr/Tar ratio on the chemotaxis behavior of

E. coli

at individual and population level was preliminarily revealed in our study. This will benefit the quantitative analysis and precise regulation of chemotaxis behavior

as well as the future applications of bacterial chemotaxis in various fields.

关键词

Keywords

references

ADLER J . Chemotaxis in bacteria: motile Escherichia coli migrate in bands that are influenced by oxygen and organic nutrients [J ] . Science , 1966 , 153 ( 3737 ): 708 - 716 .

IMAE Y , OOSAWA K , MIZUNO T , et al . Phenol: a complex chemoeffector in bacterial chemotaxis [J ] . Journal of Bacteriology , 1987 , 169 ( 1 ): 371 - 379 .

AIHARA E , CLOSSON C , MATTHIS A L , et al . Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori [J ] . PLoS Pathogens , 2014 , 10 ( 7 ): e1004275 .

RAMOS H C , RUMBO M , SIRARD J C . Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa [J ] . Trends in Microbiology , 2004 , 12 ( 11 ): 509 - 517 .

WADHAMS G H , ARMITAGE J P . Making sense of it all: bacterial chemotaxis [J ] . Nature Reviews Molecular Cell Biology , 2004 , 5 ( 12 ): 1024 - 1037 .

HOCH J A . Two-component and phosphorelay signal transduction [J ] . Current Opinion in Microbiology , 2000 , 3 ( 2 ): 165 - 170 .

ADLER J . Chemotaxis in bacteria [J ] . Annual Review of Biochemistry , 1975 , 44 : 341 - 356 .

MACNAB R M . Examination of bacterial flagellation by dark-field microscopy [J ] . Journal of Clinical Microbiology , 1976 , 4 ( 3 ): 258 - 265 .

GREBE T W , STOCK J . Bacterial chemotaxis: the five sensors of a bacterium [J ] . Current Biology , 1998 , 8 ( 5 ): R154 - R157 .

ZHULIN I B . The superfamily of chemotaxis transducers: from physiology to genomics and back [J ] . Advances in Microbial Physiology , 2001 , 45 : 157 - 198 .

NINFA E G , STOCK A , MOWBRAY S , et al . Reconstitution of the bacterial chemotaxis signal transduction system from purified components [J ] . Journal of Biological Chemistry , 1991 , 266 ( 15 ): 9764 - 9770 .

BOURRET R B , BORKOVICH K A , SIMON M I . Signal transduction pathways involving protein phosphorylation in prokaryotes [J ] . Annual Review of Biochemistry , 1991 , 60 : 401 - 441 .

MCEVOY M M , BREN A , EISENBACH M , et al . Identification of the binding interfaces on CheY for two of its targets, the phosphatase CheZ and the flagellar switch protein fliM [J ] . Journal of Molecular Biology , 1999 , 289 ( 5 ): 1423 - 1433 .

DJORDJEVIC S , STOCK A M . Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structur al motif for binding S -adenosylmethionine [J ] . Structure , 1997 , 5 ( 4 ): 545 - 558 .

YANG J Y , CHAWLA R , RHEE K Y , et al . Biphasic chemotaxis of Escherichia coli to the microbiota metabolite indole [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2020 , 117 ( 11 ): 6114 - 6120 .

NORRIS N , ALCOLOMBRI U , KEEGSTRA J M , et al . Bacterial chemotaxis to saccharides is governed by a trade-off between sensing and uptake [J ] . Biophysical Journal , 2022 , 121 ( 11 ): 2046 - 2059 .

JIANG L L , OUYANG Q , TU Y H . Quantitative modeling of Escherichia coli chemotactic motion in environments varying in space and time [J ] . PLoS Computational Biology , 2010 , 6 ( 4 ): e1000735 .

KELLER E F , SEGEL L A . Traveling bands of chemotactic bacteria: a theoretical analysis [J ] . Journal of Theoretical Biology , 1971 , 30 ( 2 ): 235 - 248 .

ZHU B Q , LI H Y , ZHANG L , et al . A Markov random field model-based approach for differentially expressed gene detection from single-cell RNA-seq data [J ] . Briefings in Bioinformatics , 2022 , 23 ( 5 ): bbac166 .

PARKINSON J S . Complementation analysis and deletion mapping of Escherichia coli mutants defective in chemotaxis [J ] . Journal of Bacteriology , 1978 , 135 ( 1 ): 45 - 53 .

BAI Y , HE C Y , CHU P , et al . Spatial modulation of individual behaviors enables an ordered structure of diverse phenotypes during bacterial group migration [J ] . eLife , 2021 , 10 : e67316 .

BRADLEY R W . An easy-to-use CRISPRi plasmid tool for inducible knockdown in E . coli [J ] . Biotechnology Reports , 2021 , 32 : e00680 .

ROCHA D J P G , CASTRO T L P , AGUIAR E R G R , et al . Gene expression analysis in bacteria by RT-qPCR [M/OL ] // Methods in molecular biology: quantitative real-time PCR . New York : Humana Press , 2020 , 2065 : 119 - 137 . ( 2019-10-02)[2025-02-01] . https://doi.org/10.1007/978-1-4939-9833-3_10 https://doi.org/10.1007/978-1-4939-9833-3_10 .

JANI S . Visualizing chemoattraction of planktonic cells to a biofilm [M/OL ] // Methods in molecular biology : bacterial chemosensing . New York : Humana Press , 2018 , 1729 : 61 - 69 . ( 2018-02-11)[2025-02-01] . https://doi.org/10.1007/978-1-4939-7577-8_6 https://doi.org/10.1007/978-1-4939-7577-8_6 .

JUSTUS C R , MARIE M A , SANDERLIN E J , et al . Transwell in vitro cell migration and invasion assays [M/OL ] // Methods in molecular biology: cell viability assays . New York : Humana Press , 2023 , 2644 : 349 - 359 . ( 2013-05-05)[2025-02-01] . https://doi.org/10.1007/978-1-4939-7577-8_6 https://doi.org/10.1007/978-1-4939-7577-8_6 .

ZANG X Q , LI Z Y , ZHANG X Y , et al . Advance in bacteria chemotaxis on microfluidic devices [J ] . Chinese Journal of Analytical Chemistry , 2017 , 45 ( 11 ): 1734 - 1744 .

ENGLERT D L , MANSON M D , JAYARAMAN A . Investigation of bacterial chemotaxis in flow-based microfluidic devices [J ] . Nature Protocols , 2010 , 5 ( 5 ): 864 - 872 .

HINKAMP P E . A table of Fikentscher K values versus relative viscosities for a concentration of 1·0 [J ] . Polymer , 1967 , 8 : 381 - 384 .

ANDERS C , NIEWOEHNER O , DUERST A , et al . Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease [J ] . Nature , 2014 , 513 ( 7519 ): 569 - 573 .

QI L S , LARSON M H , GILBERT L A , et al . Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression [J ] . Cell , 2021 , 184 ( 3 ): 844

NISHIMASU H , RAN F A , HSU P D , et al . Crystal structure of Cas9 in complex with guide RNA and target DNA [J ] . Cell , 2014 , 156 ( 5 ): 935 - 949 .

DOMINGUEZ A A , LIM W A , QI L S . Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation [J ] . Nature Reviews Molecular Cell Biology , 2016 , 17 ( 1 ): 5 - 15 .

LEE B J , JEONG H H , KANG K K , et al . Improvement of a diffusion-based microfluidic chemotaxis assay through stable formation of a chemical gradient [J ] . Chemical Engineering Science , 2019 , 202 : 130 - 137 .

JEON N L , BASKARAN H , DERTINGER S K W , et al . Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device [J ] . Nature Biotechnology , 2002 , 20 ( 8 ): 826 - 830 .

DARNTON N C , TURNER L , ROJEVSKY S , et al . On torque and tumbling in swimming Escherichia coli [J ] . Journal of Bacteriology , 2007 , 189 ( 5 ): 1756 - 1764 .

PING L Y . Cell orientation of swimming bacteria: from theoretical simulation to experimental evaluation [J ] . Science China Life Sciences , 2012 , 55 ( 3 ): 202 - 209 .

YANG Y L , SOURJIK V . Opposite responses by different chemoreceptors set a tunable preference point in Escherichia coli pH taxis [J ] . Molecular Microbiology , 2012 , 86 ( 6 ): 1482 - 1489 .

HU B , TU Y H . Precision sensing by two opposing gradient sensors: how does Escherichia coli find its preferred pH level? [J ] . Biophysical Journal , 2013 , 105 ( 1 ): 276 - 285 .

KHAN S , SPUDICH J L , MCCRAY J A , et al . Chemotactic signal integration in bacteria [J ] . Proceedings of the National Academy of Sciences of the United States of America , 1995 , 92 ( 21 ): 9757 - 9761 .

SALMAN H , LIBCHABER A . A concentration-dependent switch in the bacterial response to temperature [J ] . Nature Cell Biology , 2007 , 9 ( 9 ): 1098 - 1100 .

PAULICK A , JAKOVLJEVIC V , ZHANG S M , et al . Mechanism of bidirectional thermotaxis in Escherichia coli [J ] . eLife , 2017 , 6 : e26607 .

LAGANENKA L , LEE J W , MALFERTHEINER L , et al . Chemotaxis and autoinducer-2 signalling mediate colonization and contribute to co-existence of Escherichia coli strains in the murine gut [J ] . Nature Microbiology , 2023 , 8 ( 2 ): 204 - 217 .

SONG J , ZHANG Y , ZHANG C Q , et al . A microfluidic device for studying chemotaxis mechanism of bacterial cancer targeting [J ] . Scientific Reports , 2018 , 8 : 6394 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Research and application progress of microdroplets high throughput screening methods

An evolutionary perspective on quantitative biological principles and synthetic life design

Related Author

WANG Kunkun

QIN Weitong

YANG Guangyu

ZHAO Xiaoyu

ZHANG Hao

LI Xuefei

HU Zheng

Xiaoyu ZHAO

Related Institution

State Key Laboratory of Microbial Metabolism， School of Life Science and Technology， Shanghai Jiaotong University

Shenzhen Institute of Synthetic Biology，Shenzhen Institutes of Advanced Technology，Chinese Academy of Science

University of Chinese Academy of Sciences

⁰

A preliminary study on the regulation and analysis of indole mediated bidirectional chemotaxis behavior of Escherichia coli

DOI：10.12211/2096-8280.2025-036

摘要

Abstract

关键词

Keywords

references