Andrew J. Darwin

Andrew J. Darwin, PhD

Associate Professor, Department of Microbiology

Keywords
bacterial cell envelope functions, cellular stress, pathogens, microbiology
Summary

We use genetics, molecular biology and biochemistry, along with various infection models, to study the human pathogens Yersinia enterocolitica and Pseudomonas aeruginosa. These and other bacterial pathogens export a variety of proteins to disable or modulate host cell functions. However, production of the required protein secretion machineries has the potential to cause significant stress within the bacterial cell envelope. We have focused on well-characterized secretion systems that share a specialized outer membrane pore-forming protein known as a secretin. These secretins can mislocalize within the cell envelope and cause an acute stress that quickly leads to cell death. Therefore, bacteria must prevent or respond to this potential injury in order to successfully infect a host. Our work suggests that Y. enterocolitica and P. aeruginosa have addressed this problem in different ways.

Yersinia enterocolitica: In Y. enterocolitica, a highly specialized stress response system is required to tolerate cell injury caused by secretins. This is something called the Phage-shock-protein (Psp) system, which is essential for virulence and is also conserved in many other medically important bacteria. Mutants with a defective Psp system are quickly killed if they synthesize a secretin protein, probably due to disruption of their cell envelope. We are interested in understanding signals that activate the Psp system, studying the Psp regulatory and signal transduction mechanisms, and investigating changes in bacterial physiology when the Psp system is active.

Pseudomonas aeruginosa: P. aeruginosa is a prolific protein secretor, and has multiple secretin-containing export systems. However, it does not have a Psp system to deal with the potential for secretin-induced cell injury. We are investigating why this is the case. Our work suggests that rather than having afunctional equivalent of the Psp stress response system, P. aeruginosa might actively prevent secretin-induced stress from occurring in the first place. We have isolated a collection of P. aeruginosa mutants that are hypersensitive to secretin protein production and are characterizing the functions of the inactivated genes. This project is revealing information about P. aeruginosa functions important for its cell envelope assembly, function and integrity.

Phone

212-263-3223

Fax

212-263-8276

Academic office

450 East 29th Street

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; Moumene, Amal; Flores-Kim, Josue; Darwin, Andrew J

MBio. 2017 Sep 12; 8(5):?-?

Flores-Kim, Josue; Darwin, Andrew J

Journal of bacteriology. 2016 Dec 15; 198(24):3367-3378

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

Flores-Kim, Josue; Darwin, Andrew J

Journal of biological chemistry. 2015 May 01; 290(18):11417-11430

Flores-Kim, Josue; Darwin, Andrew J

Virulence. 2014; 5(8):835-851