Researchers in the UK have discovered that Salmonella bacteria have a “safety catch” that holds back the invasion of virulent proteins into host cells until conditions are right, and suggest this might be a target for new drugs or vaccines against Salmonella and other pathogens that work in a similar way.
The study, by researchers at Imperial College London, was published online in Science on 15 April.
Lead author Dr David Holden, a professor in Imperial’s Department of Medicine told the press that Salmonella enterica‘s way of launching virulence proteins is like a landed passenger aircraft that waits for the loading bridge to dock with the plane before the passengers can alight safely:
“… the bacterial cell waits until it has assembled a special bridge before it delivers its passengers – the virulence proteins – to the host cell,” said Holden.
The bacterial bridge is called the “T3SS assembly” (T3SS is short for SPI-2 type III secretion system): this opens a hole in the membrane of host cell vacuoles (specially enclosed pockets inside cells that serve a variety of functions), allowing entry to the virulence proteins.
Once inside the vacuole, the virulence proteins, also called effector proteins, then sabotage the cell to create an environment conducive for bacteria cell replication.
What Holden and colleagues discovered was there is a step between building the bridge, opening the hole and then allowing the virulence proteins to enter that checks the pH, or acid-alkali balance, of the vacuole environment: the safety catch is only released when the appropriate pH level is detected.
“This process is crucial for Salmonella, because if it cannot deliver these proteins properly it cannot establish an infection,” said Holden.
Holden and colleagues concluded that:
“Intravacuolar Salmonella senses host cytosolic pH, resulting in degradation of regulatory complex proteins and effector translocation.”
They told the press that it is too early to be sure, but they hope that eventually this discovery will help develop better drugs or vaccines against Salmonella-related diseases.
In humans and many animals, Salmonella causes a range of diseases including typhoid and paratyphoid fever, and the foodborne illness salmonellosis.
The study was funded by grants from the Medical Research Council and the Wellcome Trust.
“pH Sensing by Intracellular Salmonella Induces Effector Translocation.”
Xiu-Jun Yu, Kieran McGourty, Mei Liu, Kate E. Unsworth, David W. Holden.
DOI: 10.1126/science.1189000
Source: Imperial College London.
Written by: Catharine Paddock, PhD