BacterioFiles 359 - Prokaryotes Provoke Perpendicular Punishment

Strain resistant to toxin
quickly takes over colony
By Despoina Mavridou

This episode: Some bacteria produce DNA-targeting toxins, which provokes a similar retaliation from other strains. Sometimes this hurts the provoker, but sometimes it is very helpful to them!

Thanks to Dr. Despoina Mavridou for her contribution!
Download Episode (7.9 MB, 8.4 minutes)

Show notes:
Microbe of the episode: Mycobacterium virus Athena

News item

Journal Paper:
Gonzalez D, Sabnis A, Foster KR, Mavridou DAI. 2018. Costs and benefits of provocation in bacterial warfare. Proc Natl Acad Sci 115:7593–7598.

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Episode outline:

• Background: Being aggressive can be good strategy in some situations
• Prevent others from wanting to engage
• But risky; if another does engage, more danger
• And uses more energy overall
• So smartest to be tricky, use aggressiveness to maximum benefit
• One way is to provoke 2 or more threats such that they end up damaging each other
• What’s new: Now, Dr. Despoina Mavridou and colleagues Diego Gonzalez, Akshay Sabnis, and Kevin Foster, publishing in PNAS, have discovered some bacteria that use this very strategy!
• Methods: Here's Dr. Mavridou: statement 1
• Toxins called colicins, diffuse out and target essential components like DNA
• Specifically the DNA-damaging ones here induced the response (not others)
• Statement 2
• Showed this in competition experiments with different toxin-producing bacteria
• DNA targeting reduces success of competitive strategy; provoking retaliation is bad
• Worse than not producing toxin at all
• Statement 3
• So why produce these provoking toxins at all? 
• when strains were immune to DNA targeting, no harm from retaliation, only advantage
• Statement 4
• Like starting a fight between two people by smacking one from behind and ducking away
• Found that provocation can greatly affect community outcomes
• If resistant, one strain can easily dominate
• If none, whole community suffers from warfare between members
• Could be chemically induced too
• With only 2 strains, applying DNase externally could provoke warfare between them
• Summary: Bacteria that make DNA-targeting toxins can provoke a stronger counterattack from other bacteria, but this sometimes works out well for them, especially if two other strains hurt each other instead of the instigator
• Applications and implications: Treat infections – apply bacteria or just antibiotics
• Especially against biofilms
• But also must understand microbiota – unintended consequences from disruptions
• What do I think: Interesting effects on evolution
• If not resistant, avoiding provocation can be best – evolve coexistence
• But often competitive toxins can be beneficial, as shown
• Human takeaway: Be careful of how you act
• Others may be resistant and respond in harmful manner

Author Transcript:
1:
Diego and I have been working for a while on toxins produced by E. coli. We were finding that under normal conditions, a lot of these toxins are only produced by a very few cells in a bacterial population. This low but continuous level of toxin production protects the community against competitors. However, we also observed that when the same bacteria are under attack, for example if they endure damage to their own DNA, a much bigger part of the population makes toxins, to fight back.

2:
what happens when bacteria produce toxins and damage the DNA of their competitors? On the one hand, DNA is an essential component of every living being, and for this reason, it is a target for many bacterial toxins. On the other hand, as I just mentioned, DNA damage is a signal for toxin production. This means that if a bacterium produces a DNA-damaging toxin, it risks receiving a rather intense reaction from its victims.

3:
We started testing competition scenarios between provoking bacteria, meaning ones that make DNA-damaging toxins, and non-provokers. First, we found that in most one-to-one competitions, provocation backfires. There is a boomerang effect where the provoked strain launches a counterattack and harms the provoker.

4:
Things got even more interesting when we tested competition scenarios with three players. Also in this case the provoker makes the other two players produce more toxins, but here there is a catch: if the provoker is somehow protected, or immune to the toxins of its competitors, it essentially can pit the other two strains against each other. This way, the competitors wipe each other out, without harming the provoker. You could say that in this case, the provoker's behavior reminds us of divide-and-conquer strategies that are often used by animals and humans.