Microbial Mechanisms to Escape the Immune System 2

In a previous post, we discussed the mechanisms by which a Gram-positive model bacterium, Listeria monocytogenes, evades the response of a highly evolved mammalian immune system. Today, I would like to discuss the mechanisms developed by an archetypal Gram-negative bacterium, Salmonella. These two types of bacteria are very different in their physiology and they have developed very different mechanisms to avoid the defensive action of the hosts they invade. But what do these two bacteria have in common? For one, they are found in food. Salmonella can be found in chicken (and eggs), and it can also be a really serious health problem, just like Listeria.

A particular strain of Salmonella, Salmonella enterica serovar Typhi (S. Typhi), has adapted to infect only humans and is the cause of typhoid fever, a condition that can be fatal if left untreated. As S. Typhi has evolved into a host-specific pathogen, researchers have used another strain that causes a typhoid fever-like disease in mice, Salmonella enterica serovar Typhimurium, to learn about this pathogen and the disease it causes.
Salmonella enters the host through the mucosa, particularly the intestines. Once the bacteria manage to get in contact with the cells, several mechanisms will help the bug to invade the host. Although not completely understood, it is known that Salmonella, like many other Gram-negative bacteria, relies on specialized secretion systems to infect a cell. The function of these systems is to inject effector molecules that promote internalization of the bacteria by the host. The most important secretion system of Salmonella is the type III secretion system1, and it actually looks like a huge syringe, compared to the size of other protein systems.

Molecular structure model of the Type III Secretion system, a.k.a. "Needle Complex"

In a world dominated by bacteria... Ode to the type III secretion system
(Image from Art Ruby)
At the molecular level, this huge molecular complex inserts itself into the eukaryotic cell membrane and pumps bacterial molecules into the cell. These molecules (such as SipA and SipC) will in turn promote the internalization of the bacteria that is attached to the cell membrane, by manipulating the cytoplasmic actin. Remarkably, the bacteria even promote the recovery of the normal cellular architecture after its internalization is complete2.

It is for your own good...
Dark City, New Line Cinema
Once inside the host cytosol, engulfed in an early phagocytic vacuole, the bacteria will interfere with the maturation process and will drive this vacuole away from its bactericidal function. The bacteria will actively influence the vacuole environment and will turn it into a favorable niche for its survival and replication3. Thus, a main difference between the life cycle of Listeria and Salmonella is that Listeria escapes the phagosome before being killed, whereas Salmonella turns the phagosome into its home.

Yes, this bacterium will turn a hostile and harsh environment into its home sweet home...
Similar to the case of Listeria, our body has evolved to fight Salmonella. However, in cases where the immune system is compromised, or when the infection is not attended to properly and on time, the result can be fatal. We will keep on writing about mechanisms that microorganisms have developed to maximize their chances to infect a host and survive. In the meantime, I recommend the following papers to learn more about Salmonella infection.
  1. Salmonella type III secretion system
  2. Salmonella's mechanisms of evasion
  3. Salmonella exploiting host immunity
Contributed by Miguel Tam, PhD
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