Diving into the rules and strategies of bacterial warfare
The bacterial world is full of aggression. Many bacteria have developed a range of weapons to attack other strains, using poisoned molecular spears to stab one another, for example, releasing toxins to poison their enemies, and in some kamikaze cases cells even committing suicide to launch an attack. “A key focus of our research is why these systems are so often carried and why they provide bacteria benefits in terms of survival and reproduction,” explains Kevin Foster, Chair of Microbiology at the Sir Willliam Dunn School of Pathology, University of Oxford. “We’ve found that because bacteria are often territorial, it can pay to fight viciously for their territories,” he says. While studying this weaponry is fascinating from an evolutionary standpoint, it could also have implications for how we might harness bacterial competition and warfare as a new way to treat disease. The EU-funded MicroWars project took a trip to this bacterial battlefield, to find out whether these molecular weapons and strategies could be harnessed to fight bacteria that cause deadly disease. “To understand how we might do this, we need first to understand how the weapons work in practice and when they are most effective,” explains Foster.
Modelling bacterial warfare
Bacterial behaviours are difficult to spot with the naked eye, so to study them researchers need to develop proxies to see what they are doing and when. In MicroWars, the team used genetic engineering to make the bacteria glow when they use one of their weapons. This allowed them to see when and how they fought. Using mathematical and computational modelling, they could then assess natural behaviours alongside alternatives to see why they fight with their chosen methods. “One striking bacterial behaviour we studied is reciprocation, where a strain only attacks if it is attacked first,” says Foster. They studied the use of a poisoned molecular speargun in the pathogen Pseudomonas aeruginosa, finding that holding back can be an effective strategy if bacteria can take a hit and strike back harder.
New perspectives on bacterial combat
“I think the most amazing thing we learned about bacteria warfare is how plastic and responsive bacteria are when they fight,” says Foster, with many ways to detect and infer incoming attacks and respond in kind in ways that make sense strategically for their evolutionary and ecological success. One key finding was a greater understanding of why some bacteria are so heavily armed: territory is key and space is at a premium. Bacteria have developed both long and short range weapons to fight for this space, and can fight both as individuals and collectives. “This gives them many more options for combat than say many animals that typically fight alone,“ Foster says.
Developing battlefield tactics to fight gut pathogens
Having now worked out many of the rules of bacterial combat, the researchers are now trying to develop strains that can be used to eliminate and protect against pathogens in the gut. Already they have learned that an introduced strain must have its own nutrient source, and carry a sufficiently powerful weapon “We have shown that this works in the lab and now are looking to develop such things for actual use in the clinic,” says Foster.
