Cell membranes help protect a cell from the outside world and are the cell’s first defense against invading bacteria. Therefore, many pathogenic bacteria species have developed ways of getting through the cell membrane, such as type III and IV secretion systems (T3SS, T4SS). The proteins in this secretion system form a needle-like complex that can inject bacterial factors through the cell membrane directly into the host cell. Not surprisingly, Type III and IV secretion systems are found in some of the most dangerous of human pathogens such as Pseudomonas aeruginosa (pneumonia), Yersinia pestis (plague), Salmonella enterica, Shigella flexneri, Bordetella pertussis, Escherichia coli, and Vibrio cholera. The effects of the proteins injected by the type III and IV secretions systems can vary widely but, some of the more common effects include promoting the attachment and entry of bacteria into host cells, damaging cells directly, and evading the host immune response.

For example, Salmonella and Shigella can promote their own uptake into hosts cells that are not normally phagocytic. Without their secretion systems these bacteria are significantly less dangerous to humans. Other bacteria use type III and IV secretions systems to cause cytotoxicity (host cell death) which can ultimately lead to large scale tissue damage. For example, Pseudomonas aeruginosa uses a type III secretion system to inject toxins into lung cells. This toxin acts to destabilize and destroy host cell membranes, causing the cell to die, and ultimately leading to the pathology associated with pneumonia. Finally, many bacteria use their type III or IV secretion systems to evade the host immune response. One of the main activators of the host immune response is the transcription factor NF-kappaB, which acts as the master switch for a multitude of immune genes. However, Shigella flexineri injects a protein using its type III secretion system that inhibits NF-kappaB directly, thereby stopping our immune system from ever turning on.

Although type III and IV secretion systems benefit the bacteria, they do also provide unique drug and vaccine target for researchers. As antibiotic-resistant bacterial strains continue to increase and spread, many scientists are exploring alternative strategies that would decrease the virulence, or ‘disarm,' pathogenic bacteria rather than killing them directly.

Here’s another TED-Ed lesson on this topic: Insights into cell membranes via dish detergent by Ethan Perlstein.

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