Monday, October 2, 2017

BacterioFiles 312 - Antibiotic Acts As Agreement

Quorum sensing scheme
By Gluckma2, CC BY-SA 4.0
This episode: Bacteria that produce antibiotic molecule can also use it for communication between cells!

Download Episode (10 MB, 11 minutes)

Show notes:
Microbe of the episode: Rosellinia necatrix victorivirus 1

Journal Paper:
Beyersmann PG, Tomasch J, Son K, Stocker R, Göker M, Wagner-Döbler I, Simon M, Brinkhoff T. 2017. Dual function of tropodithietic acid as antibiotic and signaling molecule in global gene regulation of the probiotic bacterium Phaeobacter inhibens. Sci Rep 7:730.

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  • Using electricity to help microbes clean up pollution (paper) (see here also)
  • Photosynthetic and non-photosynthetic organisms cooperate in ocean
  • Phage therapy with CRISPR-modified viruses

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    Episode outline:
    Background: Antibiotics an amazing discovery
    Made a lot of modern medicine possible
    Much less at mercy of infectious diseases
    Surgery not a high-risk undertaking
    Penicillin from fungus, but actually many antibiotics come from bacteria themselves
    In soil, can use for competition with rivals
    Also why resistant microbes not hard to find even before we started overusing
    Either from producers resisting their own, or rivals resisting each other
    But some antibiotics we make need large amounts to work
    Not produced in such large amounts by wild producers in soil
    So what is the point of producing at all if not inhibiting rivals?
    What’s new: Now, scientists publishing in Scientific Reports have shown that antibiotics can sometimes act as chemical signals for communication between bacteria!
    Many bacteria communicate with small molecules called acyl-homoserine lactones
    Quorum sensing
    Each member of population makes a little, and when enough builds up, reaction
    Like group of people raising hands to vote; with large enough “Yea”, go forward
    No reason why other molecules couldn’t work the same way
    Marine bacterium Phaeobacter inhibens, forms strong biofilms
    Produces compound, tropodithietic acid or TDA; works as antibiotic tho not yet in use
    P. inhibens considered probiotic in aquaculture and other stuff
    TDA production regulated similarly to quorum sensing molecules; induces production of itself
    Feedback loop
    But does it affect anything else as signaling compound?
    Methods: Tested P. inhibens normal quorum sensing system
    Uses AHL; each cell produces, and has protein to sense and respond
    Knocked out either producer protein or response regulator
    Compared to wild-type, ~10% of genome had different expression
    No real difference between two knockouts
    Then tried adding TDA to see if it could substitute for AHL
    At some level, ~1 mM, TDA kills P. inhibens
    So added lower conc, only 1.5 uM
    Found that TDA restored ~7% of genome to normal; almost the same as wild-type
    Subs for AHL
    Looked at specific functions regulated
    QS downregulates motility and chemotaxis
    Confirmed in motility assay
    AHL mutants swam more/faster, unless given TDA
    Also regulates biofilm formation; QS downregulates
    Also upregulates TDA production; as known, TDA increased itself
    Summary: TDA not only an antibiotic, but at lower concentrations can act as communication between cells
    What do I think: Lots more antibiotics in the world than there used to be
    How might they be affecting things in unexpected ways? Even when diluted a lot
    Previously have also discovered other antibiotics that can act as signals, and vice versa
    Interesting to wonder whether production evolved for one purpose or other
    First one, then also coopted for other maybe
    Not as costly to use same molecule for multiple purposes
    Don't know the mechanism of TDA subbing for AHL, very intriguing
    Quorum sensing deficient mutants are like Forever Alone, no cooperation
    Might seem weird that signals downregulate both motility and biofilm production
    Aren't those kinda opposite behaviors?
    But it's like, if swimming around, just seeking place to attach, need biofilm to do so
    Once attached, not as much need to maintain; can look for opportunity to disperse
    Phaeobacter specifically likes sticking to various marine organisms to ride around
    Related: Phaeobacter likes killing algae it's riding on
    Portable food source
    Toxins used to kill algae are precursors of TDA synthesis
    Interesting possible link between molecule effects
    The world of microbes is complex and fascinating!

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