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Rocket Science in a Bacterium

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Ready, aim, fire! The armed warhead rises from its silo, breaks free of its mooring, and aims for its target. This is not some element of a Golden Dome anti-missile program, but the Type VI Secretion System (T6SS) in action, one of half a dozen such molecular machines whose job is to send payloads into other cells. You may have heard of the Type III Secretion System (T3SS) that shares a few elements with the bacterial flagellum. This one is completely different. The T6SS was described recently in Current Biology by Dor Salomon and Kim Orth of the Texas Southwestern Medical Center:

The type VI secretion system (T6SS) is a macromolecular protein secretion apparatus that is used to transfer proteins into an adjacent recipient cell in a contact-dependent manner. The T6SS is structurally similar to a contractile phage tail but in a reverse orientation: whereas the phage attaches to a bacterial cell from the outside and penetrates the membrane to deliver genetic material into the cell, the T6SS is assembled inside the cell and is used to deliver proteins out of the cell and into the recipient. [Emphasis added.]

Diagrams of the apparatus in the article look familiar to those who have seen missile silos on ships or in the ground. There’s a sheath of protein that houses the rocket. The rocket itself, tipped with a cone-shaped structure, sits below the outer membrane, ready for action. Salomon and Orth say that 13 core components make up the T6SS, not counting the “effector” molecules that comprise the payload. Here’s how launcher works:

During secretion, the sheath contracts and propels the inner tube outside of the cell and into an adjacent recipient cell, like an arrow. After secretion, the sheath is disassembled and recycled to allow the core components to be used again.

As you would expect for any anti-missile defense system, this machinery is “tightly regulated” by the bacterium. In fact, some bacteria have multiple versions of the T6SS rocket launchers that are regulated separately. “Remarkably, up to six different T6SSs can be encoded within a single bacterial genome.” Moreover, the machines are sensitive to environmental cues, like “temperature, salinity, iron concentration, pH, sub-inhibitory concentrations of antibiotics, and a density-dependent regulatory mechanism known as quorum sensing.” This allows the rockets to launch automatically if triggered by the right cues from outside.

And check this out: there are even safeguards to prevent accidental exposure to the payload.

T6SS effectors that possess antibacterial activities are produced in conjunction with a cognate immunity protein to protect the cell against self-intoxication. The immunity protein physically associates with the effector to inhibit its deleterious activity. The gene encoding the immunity protein is found adjacent to the effector gene in the same operon as a bicistronic unit. Thus, when there is an attack of one bacterial strain against another, the attacker does not kill its kin.

But don’t these machines cause disease and death? Aren’t they made to “deliver a variety of toxins into competing cells”? Indeed, Vibrio, the genus that includes cholera, and Pseudomonas, implicated in sepsis and other human diseases, contain T6SS machinery, as do at least 25 percent of gram-negative bacteria. Unfortunately, such questions are beyond the scope of the theory of intelligent design.

What we can say is that the warfare metaphor can be misleading. Nature is full of interactions between cells. We all have machines in our own cells that destroy things. For instance, “programmed cell death” (apoptosis) is a highly regulated killing process that performs many beneficial services, such as removing the webbing between fingers during fetal development. “Between 50 and 70 billion cells die each day due to apoptosis in the average human adult,” Wikipedia says. We hope you are feeling fine anyway!

So not everything that kills other cells is necessarily bad. The authors give some hints of beneficial functions for the T6SS:

The T6SS was originally described as a bacterial virulence mechanism against eukaryotic hosts. However, more recent findings show that most T6SSs are actually used as antibacterial determinants during interbacterial competition and are used to kill competing bacteria, suggesting that the T6SS can enhance environmental fitness for the attacking bacteria. There are also reports suggesting that in some bacteria the T6SS plays a role in biofilm formation, adhesion to host cells, or even in the maintenance of intracellular pH homeostasis. Recently, it was shown to act as a driver of genetic diversity by allowing bacteria to acquire DNA from dead competing bacteria during interbacterial competition. Remarkably, recent reports indicate that T6SS effectors with antibacterial cell wall degrading activities have been acquired by eukaryotes, via horizontal gene transfer from bacteria, and used to augment eukaryotic innate immune systems.

We might also note that machines with beneficial functions in one situation can get nasty in the wrong place. Oxen are good for pulling plows, but you don’t want a bull in your china shop. Similarly, Vibrio cholerae plays a beneficial role in aquatic environments, but its T6SS missiles can wreak havoc when they launch into our gut cells.

In another interesting paper in PNAS, three scientists from Italy determined that “viral decomposition provides an important contribution to benthic deep-sea ecosystem functioning.” Like the bacteria, viruses “proliferate at the expense of their hosts,” but for good reason:

Viruses are key biological agents of prokaryotic mortality in the world oceans, particularly in deep-sea ecosystems where nearly all of the prokaryotic C production is transformed into organic detritus. However, the extent to which the decomposition of viral particles (i.e., organic material of viral origin) influences the functioning of benthic deep-sea ecosystems remains completely unknown. Here, using various independent approaches, we show that in deep-sea sediments an important fraction of viruses, once they are released by cell lysis, undergo fast decomposition. Virus decomposition rates in deep-sea sediments are high even at abyssal depths and are controlled primarily by the extracellular enzymatic activities that hydrolyze the proteins of the viral capsids. We estimate that on a global scale the decomposition of benthic viruses releases ?37-50 megatons of C per year and thus represents an important source of labile organic compounds in deep-sea ecosystems. Organic material released from decomposed viruses is equivalent to 3 � 1%, 6 � 2%, and 12 � 3% of the input of photosynthetically produced C, N, and P supplied through particles sinking to bathyal/abyssal sediments. Our data indicate that the decomposition of viruses provides an important, previously ignored contribution to deep-sea ecosystem functioning and has an important role in nutrient cycling within the largest ecosystem of the biosphere.

So there’s another situation where agents of death (viruses) actually play a vital role in nutrient cycling — benefiting the global ecology.

Intelligent design enters big questions about environmental balance and habitability, and small questions about the irreducible complexity of molecular machines. The T6SS is another small wonder that rightly excites our admiration for its design. Questions about whether its functions are good or evil, though, are best left in the capable hands of philosophers or theologians.

Image: US government DOD and/or DOE photograph; public domain as work of U.S. Federal Government, via Wikicommons.

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