Switch that Enables Salmonella to Sabotage Host Cells Revealed in new Study
News Apr 23, 2010
The researchers behind the study, from Imperial College London, say that the new finding could ultimately lead to drugs that interfere with the switch in order to combat Salmonella and possibly other bacterial infections.
In humans, Salmonella causes diseases ranging from gastroenteritis to typhoid fever. It also causes similar diseases in livestock.
Before the Salmonella cell can replicate inside a much larger human or animal cell and establish an infection, it must first sabotage the cell by injecting it with a cocktail of 'virulence' proteins. These proteins interfere with the cell's defences and help the bacteria to grow.
The new research reveals that a switch needs to be triggered before the bacterial cell can inject its virulence proteins into a host cell.
First, the bacterial cell assembles a needle-like structure on its surface, to deliver the virulence proteins. Then, another set of bacterial proteins pass through the needle and poke a hole in the membrane of the host cell, creating a bridge between the bacterial cell and the host. During this time, the switch inside the bacterial cell acts like a safety catch, holding the virulence proteins back so they are not delivered prematurely.
Once the hole is created, the bacterial cell recognizes the pH of the host cell and this switches off the safety catch. This then allows the virulence proteins to be delivered through the hole into the host cell.
The lead author of the study, Professor David Holden from the Department of Medicine at Imperial College London, explained: "The way in which a Salmonella cell delivers its virulence proteins to a host cell is a bit like the way in which a parked aeroplane delivers its passengers to a terminal building. After the plane taxis to its stand at the terminal, a loading bridge is used to connect the plane to the building. Similarly, the bacterial cell waits until it has assembled a special bridge before it delivers its passengers - the virulence proteins - to the host cell.
"On a plane there's a safety catch to prevent the doors opening before the bridge is ready, to stop the passengers falling out onto the tarmac. Similarly, the bacterial cell holds back delivery of its proteins using a molecular safety catch, until it senses that the pore has been assembled. Then the safety catch switches off, and virulence proteins can be delivered in an orderly manner. This process is crucial for Salmonella, because if it cannot deliver these proteins properly it cannot establish an infection," added Professor Holden, whose work was supported by grants from the MRC and the Wellcome Trust.
The researchers stress that the research is currently at an early stage but they hope that ultimately, it might be possible to use their findings to design better drugs or vaccines to combat Salmonella-related diseases.
CRISPR Reveals New Targets for Promising Cancer DrugsNews
Novel screening method identifies new drug targets that could potentially enhance the effectiveness of PD-1 checkpoint inhibitors, a promising new class of cancer immunotherapy.READ MORE
Cell Recycling System Offers Therapeutic Entry Point for Rare Disease TreatmentNews
Scientists have demonstrated how an investigational drug works against a rare, fatal genetic disease, Niemann-Pick type C1 (NPC1).READ MORE
Study Indicates 75% of Human Genome is Non-functionalNews
An evolutionary biologist at the University of Houston has published new calculations that indicate no more than 25 percent of the human genome is functional.READ MORE
Comments | 0 ADD COMMENT
EMBL Course: Next Generation Sequencing: RNA Sequencing Library Preparation
Apr 23 - Apr 27, 2018
EMBO Practical Course: Microbial Metagenomics: A 360º Approach
Apr 23 - Apr 30, 2018
EMBL Conference: European Conference of Life Science Funders and Foundations
Apr 19 - Apr 20, 2018
EMBL Course: Next Generation Sequencing: Whole Genome Sequencing Library Preparation
Apr 16 - Apr 20, 2018