Mechanisms and regulation of horizontal gene transfer by natural transformation in Vibrio cholerae

霍乱弧菌自然转化水平基因转移的机制和调控

• 批准号: 10603610
• 负责人: Ankur Dalia
• 金额: $ 46.82万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10603610
• 关键词: ATP phosphohydrolase; Antibiotic Resistance; Area; Bacteria; Basic Science; Binding; Biological; Biological Models; Biology; Cells; Chitin; Cholera; Crustacea; Cues; DNA; DNA Binding; Environment; Fimbriae Proteins; Genes; Genetic; Horizontal Gene Transfer; Infection; Label; Membrane; Microbial Biofilms; Minor; Motor; Nutritional; Pathogenesis; Physiological; Pilum; Play; Predatory Behavior; Process; Regulation; Regulon; Role; Signal Transduction; Surface; Testing; Traction; Vibrio; Vibrio cholerae; Virulence; Virulence Factors; Work; Zooplankton; appendage; clinically relevant; combat; diarrheal disease; genetic approach; membrane activity; microbial; novel strategies; pathogen; pathogenic bacteria; resistance factors; spatiotemporal; stem; tool; transcription factor; transmission process; uptake; waterborne

Project Summary The Dalia lab studies the regulation and mechanisms of horizontal gene transfer by natural transformation (NT) using Vibrio cholerae as a model system. While this bacterium is the causative agent of the diarrheal disease cholera, we do not seek to study bacterial pathogenesis. Instead, we leverage this well- established model system and the genetic tools we have developed to characterize NT in a physiologically relevant context. NT contributes to the rapid spread of antibiotic resistance determinants and virulence factors in bacterial pathogens. Thus, characterizing the regulation and mechanisms of NT may uncover novel approaches to combat diverse clinically relevant infections. The genes required for NT are tightly regulated, and only induced when V. cholerae forms biofilms on the chitinous shells of crustacean zooplankton in the aquatic environment. The formation of chitin biofilms is also important for the survival of this facultative pathogen in its environmental reservoir, and promotes the waterborne transmission of cholera. Vibrio-chitin interactions can be easily studied in a lab setting, which provides a physiologically relevant and highly tractable model system for studying NT. In the next five years, we will focus on three major areas. First, V. cholerae uses dynamic surface appendages called type IV pili to bind to chitinous surfaces and to take up DNA for NT. The mechanisms that regulate the dynamic extension and retraction of these appendages, however, remains poorly characterized. Using tools we helped develop to label type IV pili in live cells, we will address how motor ATPases, minor pilins, and other environmental cues regulate pilus dynamic activity. Second, we will study how two membrane-embedded DNA-binding transcription factors, ChiS and TfoS, coordinate to activate the chitin regulon in V. cholerae. Membrane- embedded regulators are understudied, and this work will help elucidate the dynamics and constraints for the DNA-binding activity of membrane-embedded vs soluble transcription factors. Third, we will use a combination of cell biological and genetic approaches to study horizontal gene transfer by natural transformation. Namely, we will address the spatiotemporal dynamics of natural transformation within chitin biofilms; and the impact of neighbor predation on these dynamics. Also, we will formally test the long-standing, yet untested, hypothesis that DNA uptake during natural transformation plays an important nutritional role. Together, our basic research extends a fundamental understanding of a number of critical and conserved processes (e.g. pili, signal transduction, horizontal gene transfer) that are shared by diverse microbial species, including many pathogens.

项目总结

项目成果

Retraction ATPase Motors from Three Orthologous Type IVa Pilus Systems Support Promiscuous Retraction of the Vibrio cholerae Competence Pilus.

来自三个直系同源 IVa 型菌毛系统的回缩 ATP 酶马达支持霍乱弧菌能力菌毛的混杂回缩。

• DOI: 10.1128/jb.00126-22
• 发表时间: 2022
• 期刊: Journal of bacteriology
• 影响因子: 3.2
• 作者: Couser,Evan;Chlebek,JenniferL;Dalia,AnkurB
• 通讯作者: Dalia,AnkurB

ComM is a hexameric helicase that promotes branch migration during natural transformation in diverse Gram-negative species.

• DOI: 10.1093/nar/gky343
• 发表时间: 2018-07-06
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Nero TM;Dalia TN;Wang JC;Kysela DT;Bochman ML;Dalia AB
• 通讯作者: Dalia AB

The ChiS-Family DNA-Binding Domain Contains a Cryptic Helix-Turn-Helix Variant.

• DOI: 10.1128/mbio.03287-20
• 发表时间: 2021-03-16
• 期刊: mBio
• 影响因子: 6.4
• 作者: Klancher CA;Minasov G;Podicheti R;Rusch DB;Dalia TN;Satchell KJF;Neiditch MB;Dalia AB
• 通讯作者: Dalia AB

Membrane-localized expression, production and assembly of Vibrio parahaemolyticus T3SS2 provides evidence for transertion.

• DOI: 10.1038/s41467-023-36762-z
• 发表时间: 2023-03-02
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Kaval, Karan Gautam;Chimalapati, Suneeta;Siegel, Sara D.;Garcia, Nalleli;Jaishankar, Jananee;Dalia, Ankur B.;Orth, Kim
• 通讯作者: Orth, Kim

Retraction of DNA-bound type IV competence pili initiates DNA uptake during natural transformation in Vibrio cholerae.

• DOI: 10.1038/s41564-018-0174-y
• 发表时间: 2018-07
• 期刊: Nature microbiology
• 影响因子: 28.3
• 作者: Ellison CK;Dalia TN;Vidal Ceballos A;Wang JC;Biais N;Brun YV;Dalia AB
• 通讯作者: Dalia AB