Andrew J. Darwin

Andrew J. Darwin, PhD

Associate Professor, Department of Microbiology

Keywords
microbiology, Pseudomonas aeruginosa, Bacteria, Yersinia enterocolitica
Summary

Our lab is interested in the bacterial cell envelope, which is essential for viability and the site where numerous virulence factors are assembled or exported. Maintaining the integrity and functions of the cell envelope is essential, especially during exposure to the harsh conditions that pathogens can experience as they infect their host. We combine genetics, molecular biology and biochemistry, along with various infection models, to study the cell envelopes of two different human pathogens, Pseudomonas aeruginosa and Yersinia enterocolitica.

Pseudomonas aeruginosa: Carboxyl-terminal processing proteases (CTPs) act within the cell envelope of both Gram-negative and Gram-positive bacteria, and have been linked to the virulence of several of them. However, in most cases almost nothing is known about the mechanisms explaining those links to virulence. P. aeruginosa is a devastating human pathogen with two CTPs (CtpA and Prc), both of which have been associated with virulence, but neither of which are well characterized. We discovered that CtpA is essential for P. aeruginosa virulence because its activity facilitates the export of virulence factors. We have now identified several CtpA  proteolytic substrates, all of which are predicted to play important roles in modifying the bacterial cell wall. We are exploring how CtpA-protease activity is controlled within the cell, the physiological role of its substrates, and their impact on the cell wall and virulence. We are also broadening our interests with the goal of achieving a global understanding of the role and functions of both P. aeruginosa C-terminal processing proteases and their contributions to virulence.

Yersinia enterocoliticaY. enterocolitica is a gastrointestinal pathogen that has served as an excellent model organism to study some fundamental processes associated with bacterial pathogenesis, including invasion of host cells and the functions of virulence factor export systems. Our interest is in a highly specialized stress response system that is required to prevent lethal cytoplasmic membrane permeability. This system, known as the Phage shock protein (Psp) system, is essential for the virulence of Y. enterocolitica because it prevents its type III secretion system from causing catastrophic damage to the bacterial cell itself. The Psp system is also widely conserved, and has been associated with virulence in several other species. We are working to understand the signal transduction process that activates the Psp system, along with how the Psp proteins function to mitigate cell envelope stress.

Phone

212-263-3223

Academic office

430 East 29th Street

5th Floor, Room 504

New York, NY 10016

Lab Website
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Associate Professor, Department of Microbiology

Graduate Advisor, Sackler Training Program in Microbiology

PhD from University of Birmingham

Srivastava, Disha; Seo, Jin; Rimal, Binayak; Kim, Sung Joon; Zhen, Stephanie; Darwin, Andrew J

MBio. 2018 Jul 17; 9(4):

Flores-Kim, Josue; Darwin, Andrew J

Annual review of microbiology. 2016 Sep 08; 70:83-101

Rajkovic, Andrei; Witzky, Anne; Navarre, William; Darwin, Andrew J; Ibba, Michael

Microbial cell. 2015 Sep 23; 2(10):360-362

Rau, Reina; Darwin, Andrew J

Journal of bacteriology. 2015 Sep; 197(17):2770-2779

Rajkovic, Andrei; Erickson, Sarah; Witzky, Anne; Branson, Owen E; Seo, Jin; Gafken, Philip R; Frietas, Michael A; Whitelegge, Julian P; Faull, Kym F; Navarre, William; Darwin, Andrew J; Ibba, Michael

MBio. 2015 Jun 09; 6(3):e00823-e00823

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