When discussing pathogens infecting cells, we often turn to discussing viruses. But bacteria also have their methods of infection and one of those ways involves injecting toxic compounds into target cells. This usually helps in their bodily invasion by weakening the immune system or outright killing cells.
A Dangerous Concoction
These compounds come in the form of bacterial effector proteins that are secreted and then injected into target cells. The results of this process can vary, from interrupting enzyme production to taking control of a cell for bacterial protein synthesis to outright programmed cell death through apoptosis.
The mechanism of inserting these effector proteins into cells is through what is called a Type III (or Type IV) protein secretion machine. A recent study by researchers from Yale University succeeded in directly imaging such a machine from a Salmonella bacteria.
Using high-throughput cryo-electron tomography, a special imaging method that uses electrons for nanometer sized high quality definition of objects like with electron microscopy but with the samples cryo-frozen so that the biological parts stay intact, and sub-tomogram averaging to determine the overall shapes and parts involved, they were able to put together a structural description of the machine and its injection mechanism.
It is made up of several parts. The base of the machine is a cytoplasmic sorting platform that is capable of having conformational changes during construction of the machine, locking each subsequent piece into place. this platform also sorts and chooses the proper effector proteins to be put into the injection part of the machine.
Next is the inner membrane export apparatus that holds the selected proteins for delivery until the right chemical signal is given to release it. This in turn leads to the outer membrane portion that holds the final piece, the envelope-associated needle complex. This complex is appropriately titled the injectisome.
This final part comes to a point, similar to an actual needle or syringe ready for injecting its toxic effector proteins into the desired target.
Fighting Back With Knowledge
Having such a complete three-dimensional understanding of the structure of this machine, which is found in not only Salmonella, but also other common bacteria like Pseudomonas, Escherichia coli, Yersinia pestis, and Chlamydia, allows scientists to work on direct countermeasures to any part of the system.
The hope is that this greater knowledge will allow the development of more precise strategies and vaccines that work against the ability of this injector syringe to function. It has been seen before in other bacteria that disabling the capability of this mechanism removes almost all of the virulence abilities of the bacteria, rendering them harmless to humans.
Photo CCs: SalmonellaNIAID from Wikimedia Commons