Hans Wolf-Watz

The Type III secretion system of pathogenic Yersinia

There are three human pathogenic strains of Yersinia; Y.pestis , Y.pseudotuberculosis and Y.enterocolitica . Y.pestis is the causative agent of plague; and was responsible for the Black death during the 14th century. This family of bacteria harbours a common virulence plasmid which encodes a number of secreted proteins collectively called Yops (Yersinia outer proteins)

These proteins are expressed during infection and they are major antihost factors. One of the main functions of the Yops is to block phagocytes to engulf the pathogen. This is achieved by a specific mechanism denoted polarized translocation. The bacterium first interacts with the target cell; this intimate binding triggers increased Yop-expression followed by Yop-secretion. The Yop-effectors are then translocated into the cytosol of the target cell across the plasma membrane but only as the zone of contact between the bacterium and the eukaryotic cell. Once in the cytosol the Yop-effectors disarm the phagocyte so it can not take up the pathogen. Polarized Yop-translocation can be divided into following steps:i) The pathogen first bind to the surface of the target cell. This intimate contact leads to increased Yop-expression. ii) The bacterium secretes thereafter the Yops via the Type III secretion machinery but only at the zone of contact between the pathogen and the target cell. iii) The Yop-effectors are translocated across the target cell membrane guided by LcrV, YopB and YopD. iv) The Yop-effectors interact with their respective molecular targets to disarm the eukaryotic cell. Our aims are to dissect this chain of events on the molecular level.

We have recently employed chemical genetics in attempts to further dissect the T3SS. A class of small molecules have been identified that specifically blocks T3S of Yersinia as well as Salmonella, Pseudomonas and Chlamydia. These virulence blocking agens have the potential to be developed into a new class of antibacterial agens. We are presently pursuing this idea.

Publications

Author

Title

Year sorteringsordning

Fulltext

Weise, Christoph F
Login, Frédéric H
Ho, Oanh; et al.

Negatively charged lipid membranes promote a disorder-order transition in the Yersinia YscU protein
Biophysical Journal, 107(8): 1950-1961

2014

-

Engström, Patrik
Nguyen, Bidong D.
Normark, Johan; et al.

Mutations in hemG Mediate Resistance to Salicylidene Acylhydrazides, Demonstrating a Novel Link between Protoporphyrinogen Oxidase (HemG) and Chlamydia trachomatis Infectivity
Journal of Bacteriology, 195(18): 4221-4230

2013

-

Costa, Tiago
Amer, Ayad
Farag, Salah; et al.

Type III secretion translocon assemblies that attenuate Yersinia virulence
Cellular Microbiology, 15(7): 1088-1110

2013

-

Antti, Henrik
Fahlgren, Anna
Näsström, Elin; et al.

Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance
PLoS ONE, 8(2): e56971-

2013

Download

Frost, Stefan
Ho, Oanh
Login, Frédéric H; et al.

Autoproteolysis and Intramolecular Dissociation of Yersinia YscU Precedes Secretion of Its C-Terminal Polypeptide YscU CC
PLoS ONE, 7(11): e49349-

2012

Download

Edgren, Tomas
Forsberg, Åke
Rosqvist, Roland; et al.

Type III Secretion in Yersinia: Injectisome or Not?
PLoS pathogens, 8(5): e1002669-

2012

Download

Boehme, Katja
Steinmann, Rebekka
Kortmann, Jens; et al.

Concerted Actions of a Thermo-labile Regulator and a Unique Intergenic RNA Thermosensor Control Yersinia Virulence
PLOS PATHOGENS, 8(2): e1002518-

2012

Download

Meinzer, Ulrich
Barreau, Frederick
Esmiol-Welterlin, Sophie; et al.

Yersinia pseudotuberculosis Effector YopJ Subverts the Nod2/RICK/TAK1 Pathway and Activates Caspase-1 to Induce Intestinal Barrier Dysfunction
Cell Host and Microbe, 11(4): 337-351

2012

-

Eriksson, Jonas
Grundström, Christin
Sauer-Eriksson, A Elisabeth; et al.

Small Molecule Screening for Inhibitors of the YopH Phosphatase of Yersinia pseudotuberculosis

2012

-

Akopyan, Karen
Edgren, Tomas
Wang-Edgren, Helen; et al.

Translocation of surface-localized effectors in type III secretion
Proceedings of the National Academy of Sciences of the United States of America, 108(4): 1639-1644

2011

-


Page Editor: Hans Wolf-Watz
2010-09-08

Print page

Contact Information

Department of Molecular Biology
Umeå University
901 87 Umeå 

Visiting Address
6K och 6L, Sjukhusområdet

Tel:  +46 (0)90-7852530

Contact Form