Here’s a recent review paper about the bacterial Type VI Secretion System (T6SS), or for the laymen out there, this video gets the message across:

I was first introduced to the T6SS as part of my undergraduate studies, in a class all about the effectors of disease possessed by bacteria and other microorganisms. I’ve been learning more about it recently and it’s absolutely fascinating for a number of reasons.

For a start, it’s a bacterial machine, but the main components of it appear to be derived from an ancestral lambda T4 phage structure, meaning it was co-opted for function in the bacteria after a virus inserted its genome into the bacteria’s. We’ve all heard of Horizontal Gene Transfer (HGT), but this example takes it to another level!

To quote Schneider et al (2013):

Because VgrG proteins are orthologous to the central baseplate spikes of bacteriophages with contractile tails, we reasoned that additional structural components present in certain phage spikes might have corresponding orthologous components in T6SS. The cryoEM reconstruction of phage T4 baseplate shows that an unknown protein with a molecular weight between 7 and 23kilodaltons (kDa) binds to the tip of the β-helical domain of the central spike protein gp5 (ref. 9). We analysed all known genes encoding small proteins in phage genomes with gp5-like spikes and compared them to T6SS genes. Proteins containing the PAAR-repeat motif were strongly represented in this group with gp5.4 being the corresponding protein of T4 phage. Furthermore, genes encoding proteins with PAAR motifs were frequently found immediately downstream from vgrG-like genes suggesting that the two are genetically linked7. Therefore, we devised a strategy to test the hypothesis that these PAAR proteins were binding to the tip of gp5 and VgrG proteins.

In other words, working on the basis that the T6SS was derived from a structure in phages, they were able to compare the genes of the phage and the bacteria, looking for shared small proteins. By doing this, they found that proteins with a PAAR-repeat motif were shared, and that these genes were encoded directly downstream of the vgrG genes in the bacterial genome. This alone is a strong indicator of related function in bacteria, and it means that the genes would be expressed at the same time. They hypothesised that this ‘PAAR protein’ formed the tip of the needle in both phage and bacteria, forming a sharp spike. They were able to confirm their hypothesis by using crystallography to determine the structure of the needle. As you can see in the Figure 1, the ‘PAAR protein’ (orange) forms the tip of the needle. Another example of the theory of evolution informing cutting-edge research.


Figure 1 | Protein structure of the tip of the T6SS needle.

I don’t want you to get the impression that the T6SS is simply a copy-paste of the phage injection machine though; there are probably creationists out there who would argue that such a copy-paste event doesn’t constitute any kind of molecular evolution. While the needle and sheath structures of the T6SS are directly homologous to the structure in the phage, these alone are not enough to make the needle work in bacteria because the needle has to be anchored in a lipid membrane, unlike in phage. In order to stick in the cellular membrane, the needle structure is linked to 3 subunits: TssJ, TssL, and TssM. At least 2 of these (TssL and TssM) are homologous to proteins that function in another bacterial secretion system – the Type IV SS. Therefore you can imagine the Type VI secretion system as being a fusion between the needle of a bacteriophage and the membrane-anchoring system of the T4SS.

Figure 2 | Injection of effector molecules via the T6SS.

Simply put, it’s another example of an incredibly complex molecular machine – the kind of thing that creationists would point to and say “that could never evolve”, despite the fact that we have a pretty good understanding of what happened. Putting aside the T6SS’ evolutionary origins for a moment, let’s look into what it actually does, shall we?

It functions to essentially shoot out a sharp needle to puncture the target cell and transfer effector proteins (nucleases, amidases, phopholipases etc) into the target cell. One of the effector proteins causes actin polymerisation and cross-linking in the host cell.

Vibrio cholerae (the bacteria that causes Cholera) uses this system in an ingenious way. A population of V. cholerae in a human host will eventually come across macrophages (cells of the immune system) that would engulf and destroy them. The population allows a few V. cholerae cells to “sacrifice themselves” – being engulfed by the macrophages into the phagolysosome. Once in the phagolysosome, about to be killed, the few V. cholerae cells activate their Type VI Secretion Systems to inject effectors into the macrophage – including the effector that causes actin polymerisation and cross-linking. This has the effect of “freezing up” the macrophage, as it’s now full of cross-linked rods of actin, so it can’t engulf any more of the V. cholerae cells! So in short, this is a very ingenious way for V. cholerae to inhibit the immune response of the human body during an infection.

Even better, the protein effectors are co-expressed with so-called “immunity proteins”, which blocks the action of its corresponding effector protein (e.g. TsaB blocks VgrGC), protecting the cell expressing the T6SS from being killed if a sister cell uses its T6SS on it!
In other words, if a cell injects effectors into a sister cell, they will have the immunity proteins so won’t be killed (they literally duel over this). If the cell injects effectors into a competing bacteria of a different species or a eukaryotic cell like a macrophage, they won’t have the appropriate immunity proteins so will feel the full force of the injected effectors!

Creationists, if this complex piece of machinery didn’t evolve by the means described above, how did it arise? Did God specially create pathogens like V. cholerae to have these ingenious mechanisms to avoid the human body’s defences and cause horrific diseases? Or is the explanation simply “falldidit”, which is the only one I seem to get when I pose questions like this? How did the fall cause the creation (or even modification) of complex molecular machines?


Comments and queries are welcome.