The immune system is primed to sense invading pathogens and knock them dead. Yet bacteria have to make a living, too. They’ve evolved to evade the immune system as best as they can.
A new study led by Igor Brodsky, an assistant professor of pathobiology at the School of Veterinary Medicine, reveals how some salmonella bacteria hide from the immune system, allowing them to persist and cause a systemic infection.
The paper, published in the Journal of Experimental Medicine, looks at a component of the innate immune response called the inflammasome, a complex of proteins that triggers the release of signaling molecules that recruit other elements of the immune system to fight off the pathogen.
“We hypothesized that during the systemic phase of disease, salmonella would have some way of avoiding inflammasome activation,” Brodsky says.
To discern the bacteria’s strategy, Brodsky’s team screened a variety of mutated strains of salmonella. They found that when the gene that encodes the enzyme aconitase was mutated, the inflammasome known as NLRP3 was highly activated, leading researchers to wonder whether the normal version of aconitase might do the opposite, inhibiting the inflammasome.
Aconitase, which converts citrate to isocitrate, is a key component in the metabolic process known as the citric acid or Krebs cycle. This cycle is used by all oxygen-breathing organisms to convert sugar into energy and to produce important molecules for cell growth.
Probing deeper, the team found that mutating two other components of the citric acid cycle—the enzymes isocitrate dehydrogenase and isocitrate lyase—also led to higher activation of the NLRP3 inflammasome. Moreover, when the researchers infected mice with a strain of salmonella that had a mutated version of aconitase, the rodents were able to clear the infection, likely due to the inflammasome being activated.
Brodsky says that their results point to the possibility that the immune system may activate the inflammasome in response to the presence of citrate or some byproduct of citrate.
“Our work fits into this emerging idea that bacterial metabolites might be recognized by various components of the immune system for the purpose of either negatively or positively regulating immune responses,” Brodsky says.
Along with colleagues, Brodsky is currently working to help develop a chicken vaccine, possibly using an aconitase mutant, that could provide the animals with protection against systemic salmonella infection.
“We get salmonella from chickens that are chronically infected,” Brosky says, “so if you could prevent or limit chronic infection of chickens, that would be a nice way to limit salmonella in the food supply.”
If it is true that the results result in the possibility that the immune system may activate the inflammasome in response to the presence of citrate or some byproduct of citrate. This research also indicates that bacterial matebolites can be recognized by various components of the immune system and result in either positive or negative regulating immune response Then this research may lead to major breakthroughs in understanding the immune system better.
Since pathogens evolve and mutate every minute, any attempt of a medical intervention against salmonella infection will be worth every cent. However, possible side effects may still arise from the mutated aconitase vaccines. Therefore, Brodsky and his team, need to test the vaccines further before they use humans as their subjects. Which is why it is agreeable to start with vaccinating chickens, since that is the vector spreading salmonella bacteria. Moreover possible unwanted side effects of the vaccine can be observed before humans make use of this treatment.
However, it might also be worthwhile to find ways to manipulate the the human body’s response to the mutated salmonella pathogen to develop alternative treatments as vaccines may not be as readily available as one would want them to.
HELLO
While I strongly agree that this research and the development of these vaccines are extremely beneficial as an effective and economical method for the prevention of salmonella, I can’t help but questioning other effects that the vaccine might have. If we are vaccinating chickens and or people with mutated Aconitase, would this have any effects on the normal Aconitase in the body? and if so, what effect would this have on the Citric Acid Cycle?
Another question I would like to ask is how long it would take for the bacteria to develop another mechanism for survival, and how this would affect the current treatment methods for salmonella?
I think that it is essential that a vaccine is developed to combat salmonella, since there has been recent outbreaks in Africa of antibiotic resistant strains of the food-borne bacteria that are killing hundreds of thousands of people, as well as the annual worldwide death toll each year. If the infection of salmonella from chickens could be reduced or even stopped, it would mean that many people, right around the world would not die from this infection. The research that Brodsky’s team has done on the immune system could also be applied elsewhere in medical science. This research can help a lot of people that would not otherwise stand a chance against salmonella infections if there were not a vaccine.
The ability of salmonella bacteria to “hide” from the immune system of the host is enough to cause anyone to be terrified of this bacteria as it cannot thereby be overcome purely by the body’s immune system and will more than likely require an exterior influence to fight. Luckily the progression of the treatment has allowed for a vaccination for chickens which are the most prominent carriers as they are a staple food source for some people and the vaccination of them rather than curing the disease could save large amounts of money and lives. Furthermore if there is a vaccine available for chickens, the development of one for people will be much easier.