Andrew Darwin Lab - Microbiology

Andrew Darwin Ph.D.
Associate Professor, Department of Microbiology
450 East 29th Street
Alexandria Life Sciences Center - East Tower
Lab Rm. 321, Office Rm. 320
New York, NY 10016
Office: (212) 263-3223
Fax: (212) 263-8276
Lab: (212) 263-3224
Email: andrew.darwin@med.nyu.edu

 

KEYWORDS:

Bacteriology, bacterial genetics, Yersinia, Pseudomonas, stress response, infectious disease, gene regulation, signal transduction, membrane proteins

BIOGRAPHIC DETAILS:

Graduate Education:

1993: Ph.D. (Biochemistry), University of Birmingham, U.K.

Postdoctoral Training:

1993-1996: Cornell University
1996-2000: Washington University in St. Louis

Academic Appointments:

2001: Assistant Professor of Microbiology
2007: Associate Professor of Microbiology

Major Responsibilities:

Course Director (Fundamentals in Microbiology)
Graduate Advisor for the Microbiology PhD Training Program
Faculty Mentoring Champion for the Department of Microbiology

Major Honors:

2007: Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases
2010-2012: American Society for Microbiology Distinguished Lecturer

RESEARCH INTERESTS:

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, Yersinia enterocolitica and Pseudomonas aeruginosa.

Yersinia enterocolitica: Y. 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.

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 peptidoglycan 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.

PUBLICATIONS:

Psp Stress Response Proteins Form a Complex with Mislocalized Secretins in the Yersinia enterocolitica Cytoplasmic Membrane
Srivastava D, Moumene A, Flores-Kim J, Darwin AJ.
MBio. 2017 Sep 12;8(5). pii: e01088-17. doi:
PMID: 28900025

Interactions between the Cytoplasmic Domains of PspB and PspC Silence the Yersinia enterocolitica Phage Shock Protein Response
Flores-Kim J, Darwin AJ.
J Bacteriol. 2016 Nov 18;198(24):3367-3378
PMID: 27698088

The Phage Shock Protein Response
Flores-Kim J, Darwin AJ.
Annu Rev Microbiol. 2016 Sep 8;70:83-101
PMID: 27297125

Identification of YsaP, the pilotin of the Yersinia enterocolitica Ysa type III secretion system
Rau R, Darwin AJ
J Bacteriol. 2015 Sep 1;197(17):2770-9
PMID: 26078446

Cyclic Rhamnosylated Elongation Factor P Establishes Antibiotic Resistance in Pseudomonas aeruginosa
Rajkovic A, Erickson S, Witzky A, Branson OE, Seo J, Gafken PR, Frietas MA, Whitelegge JP, Faull KF, Navarre W, Darwin AJ, Ibba M 
MBio. 2015 Jun 9;6(3):e00823
PMID: 26060278

Activity of a bacterial cell envelope stress response is controlled by the interaction of a protein binding domain with different partners
Flores-Kim J, Darwin AJ
J Biol Chem. 2015 May 1;290(18):11417-30.
PMID: 25802329

Regulation of bacterial virulence gene expression by cell envelope stress responses
Flores-Kim J, Darwin AJ
Virulence. 2014 Nov 17;5(8):835-51
PMID: 25603429

The Pseudomonas aeruginosa periplasmic protease CtpA can affect systems that impact its ability to mount both acute and chronic infections
Seo J, Darwin AJ
Infect Immun. 2013 Dec;81(12):4561-70
PMID: 24082078

Stress relief during host infection: the phage shock protein response supports bacterial virulence in various ways
Darwin AJ.
PLoS Pathog. 2013 Jul;9(7):e1003388.
PMID: 23853578

Changes in Psp protein binding partners, localization and behaviour upon activation of the Yersinia enterocolitica phage shock protein response
Yamaguchi S, Reid DA, Rothenberg E, Darwin AJ.
Mol Microbiol. 2013 Feb;87(3):656-671.
PMID: 23290031

Links between type III secretion and extracytoplasmic stress responses in Yersinia
Flores-Kim J, Darwin AJ
Front Cell Infect Microbiol. 2012; 2:125.
PMID: 23087910

Phage shock protein C (PspC) of Yersinia enterocolitica is a polytopic membrane protein with implications for regulation of the Psp stress response
Flores-Kim J, Darwin AJ
J Bacteriol. 2012 Dec;194(23):6548-59.
PMID: 23024349

Phage shock proteins B and C prevent lethal cytoplasmic membrane permeability in Yersinia enterocolitica
Horstman NK, Darwin AJ.
Mol Microbiol. 2012 Aug;85(3):445-60.
PMID: 22646656

Stress response in the pathogenic Yersinia species
Horstman NK, Darwin AJ
In: Stress Response in Microbiology (JM Requena, ed.). June 2012, Horizon Scientific Press, United Kingdom.

Recent findings about the Yersinia enterocolitica phage shock protein response
Yamaguchi S, Darwin AJ
J Microbiol. 2012 Feb;50(1):1-7.
PMID: 22367931

FtsH-dependent degradation of Phage Shock Protein C in Yersinia enterocolitica and Escherichia coli
Singh S, Darwin AJ.
J Bacteriol. 2011 Dec;193(23):6436-42.
PMID: 21965563

The Yersinia enterocolitica Phage Shock Proteins B and C can form homodimers and heterodimers in vivo with the possibility of close association between multiple domains
Gueguen E, Flores-Kim J, Darwin AJ.
J Bacteriol. 2011 Oct;193(20):5747-58.
PMID: 21856846

Membrane association of PspA depends on activation of the phage-shock-protein response in Yersinia enterocolitica
Yamaguchi S, Gueguen E, Horstman NK, Darwin AJ.
Mol Microbiol. 2010 Oct;78(2):429-43.
PMID: 20979344

Analysis of the Yersinia enterocolitica PspBC proteins defines functional domains, essential amino acids and new roles within the phage-shock-protein response
Gueguen E, Savitzky DC, Darwin AJ.
Mol Microbiol. 2009 Nov;74(3):619-33. Epub 2009 Sep 22.
PMID: 19775245

Analysis of secretin-induced stress in Pseudomonas aeruginosa suggests prevention rather than response and identifies a novel protein involved in secretin function
Seo J, Brencic A, Darwin AJ.
J Bacteriol. 2009 Feb;191(3):898-908.
PMID: 19028883

YtxR acts as an overriding transcriptional off switch for the Yersinia enterocolitica Ysc-Yop type 3 secretion system
Axler-DiPerte GL, Hinchliffe SJ, Wren BW, Darwin AJ.
J Bacteriol. 2009 Jan;191(2):514-24.
PMID: 19011024

Regulation of the phage-shock-protein stress response in Yersinia enterocolitica
Darwin AJ.
Adv Exp Med Biol. 2007;603:167-77.
PMID: 17966413

Global analysis of tolerance to secretin-induced stress in Yersinia enterocolitica suggests that the phage-shock-protein system may be a remarkably self-contained stress response
Seo J, Savitzky DC, Ford E, Darwin AJ.
Mol Microbiol. 2007 Aug;65(3):714-27.
PMID: 17608794

YtxR, a conserved LysR-like regulator that induces expression of genes encoding a putative ADP-ribosyltransferase toxin homologue in Yersinia enterocolitica
Axler-Diperte GL, Miller VL, Darwin AJ.
J Bacteriol. 2006 Dec;188(23):8033-43.
PMID: 19011024

Multiple promoters control expression of the Yersinia enterocolitica phage-shock-protein A (pspA) operon
Maxson ME, Darwin AJ.
Microbiology. 2006 Apr;152(Pt 4):1001-10.
PMID: 16549664

PspB and PspC of Yersinia enterocolitica are dual function proteins: regulators and effectors of the phage-shock-protein response
Maxson ME, Darwin AJ.
Mol Microbiol. 2006 Mar;59(5):1610-23.
PMID: 16468999

Improved system for construction and analysis of single-copy beta-galactosidase operon fusions in Yersinia enterocolitica
Maxson ME, Darwin AJ.
Appl Environ Microbiol. 2005 Sep;71(9):5614-8.
PMID: 16151161

Genome-wide screens to identify genes of human pathogenic Yersinia species that are expressed during host infection
Darwin AJ.
Curr Issues Mol Biol. 2005 Jul;7(2):135-49.
PMID: 16053247

The phage-shock-protein response
Darwin AJ.
Mol Microbiol. 2005 Aug;57(3):621-8.
PMID: 16045608

PspG, a new member of the Yersinia enterocolitica phage shock protein regulon
Green RC, Darwin AJ.
J Bacteriol. 2004 Aug;186(15):4910-20.
PMID: 15262928

Identification of inducers of the Yersinia enterocolitica phage shock protein system and comparison to the regulation of the RpoE and Cpx extracytoplasmic stress responses
Maxson ME, Darwin AJ.
J Bacteriol. 2004 Jul;186(13):4199-208.
PMID: 15205422