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Closer Look at the T3SS Reveals Design

Evolution News
Photo: Guns on USS Iowa, by PH1 Jeff Hilton, Public domain, via Wikimedia Commons.

It is not the job of intelligent design to explain why things exist. Its only job is to distinguish between designed objects and those that can be explained by chance or natural law. Potentially harmful objects, like guns and bombs, pass the design filter. Some pathogenic bacteria have guns called secretion systems (types I-VII) with which they infect other cells, causing disease or death. This look at one such secretion system will focus on its design; philosophers and theologians can comment on the “why” questions. (See also our entry here from 2014 about the Type IV Secretion System.)

The Type III Secretion System (hence T3SS) achieved notice in the film Unlocking the Mystery of Life and in books and articles responding to evolutionist criticisms of ID. Some critics claimed that the bacterial flagellum (the icon of an irreducibly complex molecular machine) evolved from the T3SS, since it uses some of the same protein parts. In the film, biologist Scott Minnich responded to this claim of “co-option” by noting that most of the parts of the flagellum are unique. He also applied a reductio ad absurdum argument, remarking that you can only take the co-option argument so far until you end up borrowing from nothing. 

Even more important, he emphasized, are the assembly instructions that are even more complex than the machine itself — an issue never addressed by advocates of the co-option argument. Others have noted that evolutionists now consider the T3SS as a later innovation than the flagellum. If so, that would eliminate claims that the flagellum evolved from the T3SS. It also accentuates the design inference by noting that the more complex flagellum appeared without precursors. These points have been mentioned in ID literature repeatedly over the years.

New Findings

Researchers in Germany recently examined the T3SS in more detail, finding more complexities of engineering that should arouse the observer’s awe. For instance, these machines can fire effector proteins at the rate of 7 to 60 molecules per second! The machine resembles a dart gun in the bacterial cell wall that is loaded from the cytoplasm and can tunnel into a neighboring cell, probably with the aid of a pioneer translocator that opens a hole in the host membrane. Thanks to cryo-electron microscopy, the machine looks more designed than ever. The images raise and answer new questions about how it works. These include: How does the ammunition (“effector proteins”) fit into the barrel? What pushes the ammo out of the barrel with enough force to pierce the membrane of the target cell? Finally, what prevents the bacteria’s cytoplasm from leaking out of this pipe through the membrane?

Preventing Leakage

That last question about preventing leakage was answered in the paper in Nature Communications by Sean Miletic et al. The needle has a movable plug. The authors call it the M-gate.

Unfolded substrates enter the EA through a hydrophilic constriction formed by SpaQ proteins, which enables side chain-independent substrate transport. Above, a methionine gasket formed by SpaP proteins functions as a gate that dilates to accommodate substrates while preventing leaky pore formation. Following gate penetration, a moveable SpaR loop first folds up to then support substrate transport. [Emphasis added]

That EA (export apparatus) answers another question: how does the ammunition get loaded into the barrel? Figure 2 in the open-access paper shows that the EA is made up of over a dozen protein parts. The effector proteins are first unfolded in the basal body by a Q1-belt. “Unfolded substrates enter the EA,” they explain, “through a hydrophilic constriction formed by SpaQ proteins, which enables side chain-independent transport.” This provides “a rationale for the heterogeneity and structural disorder of signal sequences in T3SS effector proteins.” This gun can fire multiple kinds of ammunition!

The cryo-EM maps of the machine in Figure 1 are beautiful. The basal body and filament look like intricate networks fashioned by a skilled embroiderer. Inside the inner channel, the unfolded ammunition enters and unlocks the M-gate, which allows it to pass through. Closure of the M-gate may also push the protein through the needle, giving it some of the “oomph” it needs to fire into the host cell. How up to 60 bullets like this can translocate per second is truly astonishing.

The authors began to understand why the needle complex is rigid. It has to withstand a lot of force.

Surprisingly, the EA lumen exhibits most of the conformational changes seen in the substrate-engaged structure, an unexpected finding given the sheer size and complexity of the needle complex machine. This agrees with, albeit at lower resolutions, our earlier structure and with visualizations of in situ needle complexes contacting host cells, together suggesting that the needle complex forms a largely static channel, in contrast to other more dynamic secretion machines…. It appears plausible that this rigid architecture is a necessity to traverse the bacterial envelope, to provide a stable docking base for the dynamic components of the cytoplasmic sorting platform and simply to withstand the forces two moving cells and also the translocation process itself, exert on the secretion system.

If one visualizes the recoil action of large guns on ships as they fire, that is perhaps what the EA is doing for the T3SS — absorbing the force of the effector proteins that are being shot out of the needle.

Regarding the question of force (the “gunpowder”) for this bacterial cannon, the authors refer to a 2008 paper in Nature that suggests that proton motive force, rather than expenditure of ATP, drives the action. This would be analogous to the proton motive force in some varieties of bacterial flagella and in ATP synthase. The Type III secretion system appears to be the only system needing that kind of force to inject effector proteins directly into the target host.

An Ecological Look at Function

Secretion is ubiquitous in cells. Bacteria, archaea, and eukaryotes all have secretion machinery. It is a means by which organisms can communicate. Signaling between cells requires sharing of information which is often stored in molecules. Without this sharing of information, cells would be isolated and unaware of their environments. They would be unaware of potential threats as well. Since higher organisms, such as skunks, snakes, and porcupines have defensive and offensive weapons, it should not be surprising in principle that cells have their own — although it is rather astonishing how sophisticated they are on such a microscopic scale.

This brief look at the T3SS cannot address questions of “why” these injection machines exist, and why they cause so much harm and death to humans. It can lay some groundwork facts to guide those interested in such questions. In principle, the T3SS acts like a virus, sending foreign material into other cells and commandeering their contents. Since the vast majority of viruses are neutral or beneficial to humans, design advocates might consider whether the secretion systems in gram-negative bacteria have (or had) a beneficial purpose. Perhaps the pathogenic ones are degenerate forms. The bacteria, certainly, are oblivious to what they shoot out of their cannons; they cannot “care” whether the effector proteins are helpful or harmful, so long as the proteins can unfold and fit into the machine. Are there cases where the translocators shoot beneficial material to the host cells? Do today’s harmful T3SS represent broken machines?

Our dynamic biosphere is also filled with competing forces. Organisms push and pull on each other in ways that result in the balance of nature. One avenue for thinking about the T3SS is its possible role in regulation, limiting target cells that might otherwise get out of hand. Ancient ships needed some cats to control the rat population, and maybe cells need to regulate each other’s numbers, too. The toxic bacteria that cause human disease may have had roles in ecologies at their own level before they jumped to humans and caused trouble. 

Microbiologist Joe Francis has found, for instance, that cholera pathogens perform useful functions in estuaries, but their machines cause great harm in the human gut. In another case, doctors are finding out that antibiotic-resistant bacteria tend to predominate in sterile hospitals but go back to being docile members of soil communities where their own natural enemies keep them in check. Bats keep the bug populations down; many examples like this exist in nature. 

The Design Filter

Whatever the reason for its existence, the T3SS appears to pass the design filter. Without the Q1 unfolder, the M-gate plug, the proton motive force, and the rigid needle, it would not work. Now that the ID community knows, it can approach the phenomenon from a wider perspective. Bacteria are not selfish entities involved in a war of all against all. There’s no need to think of them as intrinsically evil, selfish killers out to get us. Most certainly, their sophisticated parts did not emerge by unguided processes of evolution. Instead, they represent elements in a large, interconnected biosphere that works quite well when everything is in balance and in its place. Medical researchers can (and should) restrict those elements that get out of hand and cause problems. Let’s take a new look at the T3SS and motivate research that brings not only deeper understanding, but solutions that contribute to human flourishing.