December 8, 2012
Salmonella Analysis Could Help Treat Bacteria-Related Illnesses
redOrbit Staff & Wire Reports - Your Universe Online
A study from Cambridge University researchers shines new light on exactly how Salmonella spreads throughout a person's body -- work that could help medical experts overcome roadblocks in the development of vaccines and other forms of therapy to help combat the disease-causing bacteria.
By analyzing salmonellae, which are typically found growing inside of immune system cells during an infection, the researchers discovered the pathogens must also "escape from infected cells to spread to distant sites in the body, avoiding the local escalation of the immune response and thus playing a 'catch me if you can' game with the host immune system," the university explained in a December 6 statement.
Laboratory experiments have suggested replication of Salmonella enterica within host cells in vitro depends partially on the bacteria creating a syringe-like structure and injecting proteins into a host cell. That results in enhanced bacterial replication within that cell, the university said, and the structure is encoded by genes in an area of the bacterial chromosome known at the Salmonella Pathogenicity Island 2 (SPI-2).
"Translating this cell culture work into whole animals, it has become accepted dogma that the SPI-2 T3SS is also required for bacterial intracellular replication in cells inside the body," they explained. "However, using fluorescence and confocal microscopy (which are imaging techniques), the Cambridge team has dispelled this dogma concerning the requirement for the SPI-2 T3SS for intracellular replication in the body.
"The researchers have shown that mutants lacking SPI-2 can reach high numbers within individual host cells, a situation that does not happen in in vitro cell culture," the university continued, adding that the experts "investigated this phenomenon further and made the surprising discovery that salmonellae lacking the SPI-2 T3SS remain trapped inside cells and cannot spread in the body. One idea is that this will in turn lead to the arrest of bacterial division as a consequence of spatial or nutritional constraints."
Even though the bacteria can increase to high levels per cell, the mutant Salmonellae had a diminished ability to exit the cell they originally infected, and thus were far less likely to spread to other cells throughout the body.
As such, the university says their discovery, which is detailed in the latest edition of the journal PLoS Pathogens casts doubt upon the validity of some in vitro experiments which fail to effectively capture the complex structures of mammals and other biological beings.
"Salmonella enterica is a major threat to public health, causing systemic diseases (typhoid and paratyphoid fever), gastroenteritis and non-typhoidal septicaemia (NTS) in humans and in many animal species worldwide," the university explained, with lead researcher Dr. Andrew Grant calling it "a significant public health threat.
"Unfortunately, effective treatments and vaccinations have thus far eluded scientists, in part because of a lack of understanding of how and why the bacteria spread," Grant added. "This research provides critical insight which will hopefully lead to new medical interventions for this disease."