Monday, March 12, 2018

BacterioFiles 331 - Password Protein Poisons Pairings

Myxobacteria fruiting bodies
By Trance Gemini, CC-BY 3.0
This episode: How social bacteria societies function: by sharing enzyme packages with each other that can contain toxins that are deadly for rivals but not for friends!

Thanks to Chris Vasallo for his contribution!
Download Episode (12.4 MB, 13.6 minutes)

Show notes:
Microbe of the episode: Propionibacterium virus PAD20

News item

Journal Paper:
Vassallo CN, Cao P, Conklin A, Finkelstein H, Hayes CS, Wall D. 2017. Infectious polymorphic toxins delivered by outer membrane exchange discriminate kin in myxobacteria. eLife 6:e29397.

Other interesting stories:
  • Attaching proteins to little bioplastic beads to make useful nanoparticles (paper)
  • Fungi are very important for nutrient cycling in the world
  • Friendly soil microbes inject plant pathogens with toxin
  • Microbes are carried around the world through the atmosphere
  • Arctic algae can grow even in super cold and dark conditions

  • Post questions or comments here or email to Thanks for listening!

    Subscribe: iTunes, RSS, Google Play. Support the show at Patreon, or check out the show at Twitter or Facebook.

    Episode outline:
    • Background: Challenge: how to make individuals function as unit
      • Important for human institutions
      • Also for some microbes
    • Myxobacteria, live in soil, often act as group together
      • Myxococcus xanthus
      • Swarm around and eat other bacteria
      • Share prey and digestive enzymes and such
      • When food scarce, act like slime mold and form fruiting bodies
      • Spread spores to new locations while others remain behind, sacrificed
    • But successful systems attract parasites
      • Strains that can take without giving have advantage
      • How can microbe groups prevent this?
    • What’s new: Now, Chris Vasallo, Pengbo Cao, Austin Conklin, Daniel Wall, and their UC Santa Barbara coauthors Hayley Finkelstein and Chris Hayes, publishing in eLife, have discovered one method of policing: a sort of lethal handshake!
    • Previous stories
      • 136: M. xanthus forms membrane tubes between cells 
      • 153: exchange membrane proteins with each other, can distinguish in-group vs. out-group
    • Methods: Observed mixtures on plates, nonmotile strain could inhibit spread of motile strain
      • Result of killing somehow, but how?
      • Discovered related to gene sitA, Swarm Inhibition Toxin
        • Protein found in outer membrane
      • Next to it is sitI, looks like family of immunity proteins
        • Bacteria need immunity to their own toxins, of course
    • Tried knocking out or adding these genes to strains
      • No swarm inhibition when toxin gene knocked out
      • Also if protein transfer gene gone
      • Adding immunity gene to motile allowed swarming
      • Adding genes to another strain allowed it to inhibit swarming
      • As Chris Vasallo describes: Statement 1
    • In other strains, found other versions of toxin/immunity genes, possibly >100
      • Similar but not same
      • Each sitI version gives immunity to paired sitA
      • Not all equally potent though
    • Attached fluorescence protein to toxin and observed it transferred between strains
    • Tested compatibility on plates by spotting cells nearby
      • If swarms combined, compatible
      • Found that different versions had very clear dividing lines
    • So sorta like “what’s the password? Wrong answer”
    • Found something else too: statement 2
      • So one strain can inhibit another that outnumbers it 40:1 or even 1000:1
      • Tested with 3 strains with various features
        • One intermediate, two that could only interact with intermediate
        • Both could be inhibited despite toxin producer only targeting one
        • If intermediate couldn’t interact at all, no inhibitions
      • So instead of password, like poisoned handshake, poison spreads
      • Must not be deadly until after it has chance to spread to others
    • Found that having toxin production was very important to competitive success
    • Summary: Social Myxobacteria produce different toxins that can kill rivals but not friends when they exchange outer membrane proteins, and poisoned victims can spread toxins to other cells
    • Applications and implications: Important for understanding origin and mechanism of multicellularity
      • Statement importance
    • What do I think: Extra protection from infiltration by rivals
      • To get benefits of cooperation, 1st cell must be able to communicate
        • Have same language i.e. compatible membrane transfer proteins
      • Then must have immunity to any toxins transferred
      • If conditions met, outcome good; if not, either neutral or very bad
    • Could sneaky rival collect immunity genes?
      • Technically, but if not selected by other cells, unlikely
      • Costs resources to copy gene and produce proteins
      • On other hand, can be advantage to acquire cos can use against rivals
        • And if lost, surrounding cells that still had it could kill
    • More work to do, here's Chris again: Future
    • Human takeaway: Opening self up can be risky, but with good precautions, beneficial

    So here, in this paper, we found that, to make sure they exchange cellular components with the right sibling cells, they deliver variable toxins during this process. So myxobacteria that have immunity to the toxin are considered sibling cells, but myxobacteria that don't have immunity are considered competitors and are poisoned.

    Interestingly, we found that the toxins are infectious, meaning they can be delivered to cells that never made direct contact with the toxin producer. And they do this by using an initial target cell as a carrier. So in other words, the toxins are serially transferred from cell to cell.

    Myxobacteria have many coordinated behaviors, like development, swarming, and predation by a wolfpack strategy. What's important is they have also made the transition to multicellularity, which is rare for bacteria. So unlike multicellular animals or plants, their bacterial cells are not always physically linked. So these bacteria have to discriminate which cells to cooperate with and which cells to compete with, among the millions of different microorganisms in a small patch of soil. So we think toxin systems like the one we discovered are one mechanism that supports a bacterial transition to multicellularity, in this case by ensuring that competitors can't infiltrate and exploit a community of cooperators.

    Future Direction:
    As far as future work, we're interested in how these toxins enter the cytoplasm of the target cell once they're delivered, and also how these toxins help define kin groups in wild soil populations. But the main focus of the lab is outer membrane exchange, and we are working toward understanding the mechanism that allows this fascinating and rare behavior.


    1. Could the immunity genes be transfered into other microbes to successfully make them immune to the toxins that are being produced by Myxococcus xanthus?

      1. Yes, in fact, whereas many genes can be transferred horizontally through bacteriophage, DNA uptake, conjugation, etc., these toxin and immunity genes of M. xanthus seem to be spread around at a higher rate than usual. The reason is likely that once they are incorporated into the genome, they are not lost since deletion would mean that that cell is killed by its neighbors (it has lost its immunity). Its a selfish and addictive DNA element so-to-speak. If by other microbes you mean non-Myxobacteria, then it doesn't matter because Myxo doesn't use this system to attack non-Myxobacteria. The best example of an interspecies bacterial weapon is the type VI secretion system, I suggest you look into it if you're interested... its really quite a cool tool that many gram-negative bacteria use for competition.

    2. This comment has been removed by the author.

    3. Is the Myxococcus xanthus the only bacteria that uses passive immunity and toxicity for collaboration and survival of it's own species? Or is common with other strands of bacteria as well?

      1. Myxococcus is pretty unique in its ability to share outer membrane contents with each other. However, lots of different kinds do produce antibacterial toxins to reduce competition from other bacteria. Many of the antibiotics we have used in medicine were discovered being produced by bacteria, particularly the genus Streptomyces, and genes antibiotic resistance (the "immunity" half of the pairing) have been around since before we started using antibiotics, found in all kinds of different environments.

        Here's a pretty interesting example of one kind of bacteria producing toxins to kill others and steal their genes: