Weightlessness has the potential to enhance a regular virus and increase its ability to kill stubborn bacteria. In an experiment under a strictly regulated condition of the International Space Station (ISS), scientists observed an ancient biological confrontation, that of Escherichia coli and the T7 bacteriophage, assume new rules. It was not an oddity of space that was paid. Certain genetic adaptations that assisted phages to deal with orbit subsequently found applications in enhanced activity against UTI-inducing strains of E. coli on the earth that generally resist such a phage.
It focused on phages, viruses that infect bacteria, and the arms-race reasoning that is typically at play when these two groups come in contact with each other: bacteria evolve defenses, phages develop counter-mechanisms, and the process repeats. At orbit however, the physics that dances these encounters change. In the absence of stirring enhancing buoyancy cells and viruses collide less, and local nutrient and waste localization become more difficult to dissipate. The ISS was used as an experiment on how that transformed “collusion economy” will transform evolution itself.
The combinations of bacteria and phage were incubated by scientists in almost a weightless state during 25 days, and parallel cultures were performed under the influence of the Earth gravity. The general trend was a postponement, then separation. The infection under microgravity did not continue on its merry way with the vigor with which it should have developed in terrestrial laboratory cultures, but began slowly and gradually regained its strength. The attack by the phage was still successful, but the path it followed was genetic and functional in another way. This has been outlined in the study as follows: Space fundamentally alters the way the phages and the bacteria interact: infection becomes slower, and the two creatures move along a new path than on Earth.
In genomes it is possible to read that path. Bacteria subjected to phage in orbit gained unique mutations such as those in the outer-membrane characteristics which the phage has to identify before it can inject its DNA. The same space condition also subjected bacterial metabolism and survival programs, which drove mutations associated with stress response and nutrient management. One set of changes in particular was observed in mlaA, a membrane-associated gene that is involved in the management of phospholipids-one of the ways that the manipulation of fluid mixing and local chemistry can strain the bacterial surface, the surface that phages are forced to attach to.
It was not a simple trick that phages were adapted by. Whole-genome sequencing revealed mutations of several phage genes including infection mechanics and host interaction components. To map the most significant alterations, the team employed deep mutational scanning of the phage receptor-binding protein which is an essential structure that enables T7 to latch onto a surface of a particular bacterium. Patterns of substitution which were more microgravity-enriched were found, and the pattern preferred on Earth was no longer preferred on the host – evidence that the host is not the same as the phage in space, and that the optimum solutions of the phage vary to reflect it.
The most consequential discovery was made after the space-grown winners were re-introduced to the earthly tests. Microgravity enhanced phage variants which exhibited higher activity against uropathogenic strains of E. coli that cause urinary tract infections- strains that are usually resistant to wild-type T7. The scientists then designed phages with a combination of space-selected mutations and discovered that these designs were superior to those on Earth in their capability to counter such UTI isolates.
The clinical background adds to the topicality: over 90 percent of the bacteria that cause UTIs are resistant to one or more antibiotics. The finding of the study does not put spaceflight as a quick fix to medicine, but rather as a discovery space whereby the various physical limitations reveal evolutionary possibilities that cannot be seen under normal lab flasks.
The second implication remains within the engineering domain, however, as long as humans remain in orbit, microbial ecosystems and infections become both operational and biological issues. Knowledge of the behaviour of phage-bacteria coevolution under non-mixing fluids teaches both directions, in what ways phage therapies can be used to defend astronaut health in microgravity, and how we can exploit the non-standard selection pressures of microgravity to broaden the design space of phage therapies on Earth.
