The Secret Lives of Bacterial Toxins

Bacteria spend a lot of time and energy avoiding detection by the immune system (no self-respecting pathogen gives up without a fight). One mechanism is to avoid being eaten by phagocytes, white blood cells charged with seeking out and destroying foreign invaders (the video below shows a phagocyte chasing bacteria in real-time). Some bacteria, such as Staphylococcus aureus, do this by forming impenetrable biofilms, while E. coli was shown to produce a protective cell-surface capsule after prolonged growth with phagocytes. Other species produce toxins to "poison" the host immune response.






















ACD (for "actin crosslinking domain") is a toxin produced by a handful of bacterial species. Vibrio cholera and its close relative Vibrio vulnificus (bacteria that cause cholera and shellfish-associated food poisoning, respectively), along with Aeromonas hydrophila, all produce ACD.

Researchers knew that ACD effectively stopped immune cells from approaching and engulfing bacteria, but the precise mechanism of action was unclear. It was thought that ACD simply bound to actin monomers, preventing them from polymerizing into the functional filaments that allow immune cells to change their shape and engulf bacteria. This would require large amounts of ACD to be present in each host cell, however, researchers knew that only a small amount of ACD was required to disarm the host. This led David Heisler, a graduate student at The Ohio State University, to dig a little deeper. He suspected that ACD targeted other host proteins in addition to actin. Heisler and colleagues published their findings in the July 31 issue of Science.

In order to polymerize into filaments, actin monomers require the help of an additional protein called formin. Heisler demonstrated that in addition to binding actin, ACD effectively prevented formin from polymerizing free actin into functional filaments. Essentially, formin has a greater affinity to interact with ACD/actin complexes, than with actin alone. Thus, small amounts of ACD are able to start a chain reaction that "poisons" all of the actin in the cell.

Or, as senior author Dmitri Kudryashov puts it, "it appears that this toxin followed some of the most sophisticated battlefield strategies long before they were invented by humans: it recognizes that to win the war, one doesn't need to kill all the soldiers. All that is needed is to send in a spy to recruit a few soldiers who will betray their own army and neutralize the officers".



Sources: Eurekalert, The Scientist