A closer look at the T3SS reveals the design

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

It’s not smart design’s job to explain why things exist. Its only job is to distinguish between designed objects and those which can be explained by chance or natural law. Potentially dangerous objects, such as 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 such a secretion system will focus on its design; philosophers and theologians can comment on “why” questions. (See also our entry here from 2014 on the type IV secretion system.)

The type III secretion system (hence T3SS) was noticed in the movie Unlock the mystery of life and in books and articles responding to evolutionary critiques of identity. Some critics have claimed that the bacterial flagellum (the icon of an irreducibly complex molecular machine) evolved from T3SS because it uses some of the same protein parts. In the film, biologist Scott Minnich responded to this “cooptation” claim by noting that most parts of the flagellum are unique. He also applied a reductio ad absurdum argument, noting that you can only push the co-option argument until you end up borrowing from nothing.

More importantly, he pointed out, the assembly instructions are even more complex than the machine itself – an issue never before addressed by supporters of the co-opting argument. Others have noted that evolutionists now view T3SS as a post-flagellum innovation. If so, it would eliminate claims that the flagellum evolved from T3SS. He also emphasizes design inference by noting that the more complex flagellum appeared without precursors. These points have been mentioned repeatedly in the ID literature over the years.

New discoveries

German researchers recently examined the T3SS in more detail, finding more engineering complexities that should elicit the admiration of the observer. For example, these machines can trigger effector proteins at a rate of 7 to 60 molecules per second! The machine looks like a dart gun in the bacterial cell wall that is loaded from the cytoplasm and can penetrate a nearby cell, presumably using 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 ammunition (“effector proteins”) fit into the barrel? What is pushing the ammunition out of the barrel with enough force to pierce the membrane of the target cell? Finally, what prevents the cytoplasm of the bacteria from escaping from this pipe through the membrane?

Prevent leaks

This last question on leak prevention was answered in the article in NOTature Communications by Sean Miletic et al. The needle has a movable stopper. The authors call it the M-gate.

Unfolded substrates enter EA through a hydrophilic constriction formed by SpaQ proteins, allowing side chain independent substrate transport. Above, a methionine seal formed by the SpaP proteins functions as a gate which expands to accommodate the substrates while preventing the formation of leaky pores. After entering the door, a movable SpaR loop folds up first to then take charge of the transport of the substrate. [Emphasis added]

This EA (Export Device) answers another question: how ammunition is loaded into the barrel? Figure 2 of the open access article shows that EA is made up of more than a dozen parts of proteins. The effector proteins are first unfolded in the basal body by a Q1 belt. “The unfolded substrates enter the EA,” they explain, “through a hydrophilic constriction formed by the SpaQ proteins, which allows 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 several types of ammunition!

The cryo-EM cards of the machine in Figure 1 are magnificent. The basal body and filament look like intricate networks fashioned by an experienced embroiderer. Inside the inner channel, the unfolded ammunition enters and unlocks door M, allowing it to pass. Closing the M gate can also push the protein through the needle, giving it some of the “punch” it needs to fire in the host cell. The translocation of up to 60 bullets like this per second is truly amazing.

Authors began to understand why the needle complex is stiff. He has to resist a lot of force.

Surprisingly, EA light exhibits most of the conformational changes observed in the structure engaged with the substrate, an unexpected discovery given the size and complexity of the complex needle machine. This is consistent with, albeit at lower resolutions, our previous structure and with visualizations of in situ needle complexes in contact with host cells, together suggesting that the needle complex forms a largely static channel, unlike other more dynamic secretion machines…. It seems plausible that this rigid architecture is a necessity to cross the bacterial envelope, to provide a stable anchoring base for the dynamic components of the cytoplasmic sorting platform and simply resist the forces two mobile cells and also the translocation process itself, exercise on the secretion system.

If one visualizes the recoil action of the large guns on ships as they fire, perhaps this is what the EA does for the T3SS – absorbing the force of the effector proteins that are fired from the needle.

Regarding the issue of force (“gunpowder”) for this bacterial gun, the authors refer to a 2008 article in Nature this suggests that the driving force of the proton, rather than the expenditure of ATP, is directing the action. This would be analogous to the driving force of protons in certain varieties of bacterial flagella and in ATP synthase. The type III secretion system appears to be the only system requiring this type of force to inject effector proteins directly into the target host.

An ecological look at function

The secretion is ubiquitous in the cells. Bacteria, archaea and eukaryotes all have a secretion mechanism. It is a means by which organisms can communicate. Signaling between cells requires the sharing of information that is often stored in molecules. Without this sharing of information, cells would be isolated and ignore their environment. They would also not be aware of potential threats. Since higher organisms, such as skunks, snakes, and porcupines have both defensive and offensive weapons, it shouldn’t be surprising in principle that cells have theirs – although it is rather astonishing to see how sophisticated they are on such a microscopic scale.

This brief overview of T3SS cannot answer the questions of “why” these injection machines exist, and why they cause so much harm and death to humans. It can lay a factual foundation to guide those interested in such questions. In principle, T3SS acts like a virus, sending foreign material into other cells and requisitioning their contents. Since the vast majority of viruses are neutral or beneficial to humans, proponents of the design might question whether the secretion systems of Gram-negative bacteria have (or had) a beneficial purpose. Maybe the pathogens are degenerate forms. Bacteria, of course, do not know what they get from their guns; they can’t “care” whether the effector proteins are useful or harmful, as long as the proteins can unfold and fit into the machine. Are there instances where translocators project beneficial material to host cells? Do today’s harmful T3SSs represent broken machines?

Our vibrant biosphere is also filled with competing forces. Organisms push and pull on each other in a way that balances nature. One avenue for reflection on T3SS is its possible role in regulation, by limiting target cells that might otherwise get out of hand. The old ships needed certain cats to control the rat population, and maybe the cells needed to regulate the number of their mutuals as well. The toxic bacteria that cause human illness may have played a role in ecologies at their own level before jumping to humans and causing problems.

Microbiologist Joe Francis has found, for example, that cholera pathogens perform useful functions in estuaries, but their machines cause severe damage to the human gut. In another case, doctors find that antibiotic-resistant bacteria tend to predominate in sterile hospitals, but once again become docile members of soil communities where their own natural enemies control them. Bats reduce insect populations; many examples like this exist in nature.

The design filter

Whatever the reason for its existence, the T3SS seems to pass the design filter. Without the Q1 unfolding, the M-gate plug, the proton driving force, and the stiff needle, this wouldn’t work. Now that the ID community knows it, they can approach the phenomenon from a broader perspective. Bacteria are not selfish entities involved in an all-on-all war. You don’t have to think of them as inherently evil and selfish killers to catch us. Most certainly, their sophisticated parts did not arise through unguided evolutionary processes. Instead, they represent pieces of a large, interconnected biosphere that works quite well when everything is in balance and in its place. Medical researchers can (and should) restrict what gets out of hand and causes problems. Let’s take a fresh look at T3SS and motivate research that not only brings deeper understanding, but solutions that contribute to human flourishing.

About Lucille Thompson

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