Bacterial Pathogenesis & Signal Transduction Lab

Prof Linda J Kenney

Linda J Kenney Lab2018-09-24T13:20:45+08:00
BACTERIAL PATHOGENESIS & SIGNAL TRANSDUCTION LAB

Linda J Kenney’s laboratory employs interdisciplinary approaches to understand environmental signaling in bacteria, host specificity of bacterial pathogens, gene silencing and relief of silencing in Salmonella

Recent Featured Research

News & Announcements
KENNEY LABORATORY RESEARCH

The Kenney laboratory is dedicated to solving important problems in bacterial mechanotransduction related to pathogenesis.

Bacterial pathogenesis involves the programmed changes in gene expression to evade host defense systems through sensing the host environment both physically and chemically.

Research

KENNEY LABORATORY RESEARCH

In bacteria, signal transduction occurs largely via two-component regulatory systems. These systems employ an inner membrane histidine kinase (the sensor) and a cytoplasmic response regulator. Environmental sensing is in most cases directly coupled to regulation of gene expression.

The two components communicate via a series of phosphorylation/ phosphotransfer reactions. The sensor kinase is autophosphorylated by ATP at a conserved histidine residue upon activation by environmental stress. The sensor kinase then transfers the phosphoryl group to a conserved aspartate on the response regulator. Phosphorylation of the response regulator often increases its affinity for DNA leading to transcriptional activation or repression, depending on the mode of action.

KENNEY LABORATORY RESEARCH CONT.

The EnvZ/OmpR system that we study responds to osmotic changes and controls the expression of the outer membrane proteins OmpF and OmpC. OmpR is an important global regulator and plays a major role in regulating virulence genes in many pathogens, including Salmonella, Yersinia, Shigella and E. coli.

A central question in the EnvZ/OmpR two-component system that we study (and an unanswered question in most other sensor kinases as well) is how does a change in the osmolality of the external environment (the signal) result in the differential regulation of outer membrane porin gene expression (the output)?

Current Projects

RECENT WORK

The Kenney laboratory is interested in signal transduction and the regulation of gene expression in prokaryotes. In particular, we are studying the two-component regulatory system EnvZ/OmpR that regulates the expression of outer membrane proteins as well as many other genes.

Our present work focuses on how OmpR activates genes required for systemic infection  (located on Salmonella pathogenicity island 2) in Salmonella enterica.

Current Projects

Structural Analysis of SPI-2 needles

Using cryoelectron microscopy to perform structural analysis of the macromolecular complex of the SPI-2 secretory apparatus

Silencing and Anti-Silencing in Salmonella Pathogenesis

Characterizing the binding properties of the H-NS homologue StpA

The Mechanism of Osmosensing by EnvZ and other HKs

Mapping conformational changes in EnvZ associated with osmotic stress

Super-Resolution Microscopy of EnvZ, OmpR, H-NS, and Chromosomal Imaging

Examining OmpR/DNA interactions using PALM

Porin Gene Transcription in Single Cells

Transcription of GFP enables us to see how expression levels change in response to osmolality

Recent Publications

  1. Desai SK, Padmanabhan A, Harshe S, Zaidel-Bar R, and Kenney LJ. Salmonella biofilms program innate immunity for persistence in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 2019;. [PMID: 31160462]
  2. Ottemann KM, and Kenney LJ. Editorial overview: Host-pathogen interactions: bacteria. Curr. Opin. Microbiol. 2019; 47:iii-v. [PMID: 31138403]
  3. Liew ATF, Foo YH, Gao Y, Zangoui P, Singh MK, Gulvady R, and Kenney LJ. Single cell, super-resolution imaging reveals an acid pH-dependent conformational switch in SsrB regulates SPI-2. Elife 2019; 8. [PMID: 31033442]
  4. Chakraborty S, and Kenney LJ. A New Role of OmpR in Acid and Osmotic Stress in Salmonella and E. coli. Front Microbiol 2018; 9:2656. [PMID: 30524381]
  5. Kenney LJ. The role of acid stress in Salmonella pathogenesis. Curr. Opin. Microbiol. 2018; 47:45-51. [PMID: 30529007]
  6. Ghosh M, Wang LC, Huber R, Gao Y, Morgan LK, Tulsian NK, Bond P, Kenney LJ, and Anand GS. Engineering an Osmosensor by Pivotal Histidine Positioning within Disordered Helices. Structure 2018;. [PMID: 30503779]
  7. Gulvady R, Gao Y, Kenney LJ, and Yan J. A single molecule analysis of H-NS uncouples DNA binding affinity from DNA specificity. Nucleic Acids Res. 2018;. [PMID: 30239908]
  8. Mather AE, Phuong TLT, Gao Y, Clare S, Mukhopadhyay S, Goulding DA, Hoang NTD, Tuyen HT, Lan NPH, Thompson CN, Trang NHT, Carrique-Mas J, Tue NT, Campbell JI, Rabaa MA, Thanh DP, Harcourt K, Hoa NT, Trung NV, Schultsz C, Perron GG, Coia JE, Brown DJ, Okoro C, Parkhill J, Thomson NR, Chau NVV, Thwaites GE, Maskell DJ, Dougan G, Kenney LJ, and Baker S. New Variant of Multidrug-Resistant Salmonella enterica Serovar Typhimurium Associated with Invasive Disease in Immunocompromised Patients in Vietnam. MBio 2018; 9(5). [PMID: 30181247]
  9. Gao Y, Spahn C, Heilemann M, and Kenney LJ. The Pearling Transition Provides Evidence of Force-Driven Endosomal Tubulation during Salmonella Infection. MBio 2018; 9(3). [PMID: 29921673]
  10. Dykas MM, Desai SK, Patra A, Motapothula MR, Poddar K, Kenney LJ, and Venkatesan T. Identification of Biofilm Inhibitors by Screening Combinatorial Libraries of Metal Oxide Thin Films. ACS Appl Mater Interfaces 2018;. [PMID: 29553712]

Lab Members

CURRENT LAB MEMBERS