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Sunday, 19 August 2018 21:24

Staphylococcus Stops Skin Swellings - BacterioFiles 352

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Published in Bacteriofiles

This episode: A harmless strain of bacteria on the skin produces a compound that can prevent tumors from forming!

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(9.2 MB, 10 minutes)

Show notes: 

bf352staphepiMicrobe of the episode: Hamiltonella virus APSE1

News item

Journal Paper:
Nakatsuji T, Chen TH, Butcher AM, Trzoss LL, Nam S-J, Shirakawa KT, Zhou W, Oh J, Otto M, Fenical W, Gallo RL. 2018. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Sci Adv 4:eaao4502.

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Episode outline:

  • Background: Microbiota important for most parts of body, function of immune system
    • Gut but also skin and others
  • Help defend against pathogens like Staphylococcus aureus
  • Can also help regulate inflammation after injury
  • What’s new: Now, scientists publishing in Science Advances have discovered another useful function of skin microbes—protecting against cancer!
  • Methods: Were testing strains of Staphylococcus that live on healthy skin for antimicrobials
    • Found one S. epidermidis that can secrete inhibitor of Streptococcus pathogens
    • Purified and identified as a small molecule, not a protein: 6-N-hydroxyaminopurine
      • Or 6-HAP
    • Synthesized specifically by the bacteria, not byproduct of metabolism
  • 6-HAP similar in structure to nucleic acid base, adenine, or A of AGCT
    • Might interact with DNA/RNA metabolism somehow
    • So tested with DNA polymerase
      • 6-HAP inhibited DNA synthesis when addition of adenine nucleotide required
    • So can prevent DNA synthesis and therefore can prevent cell replication/proliferation
  • Possibly useful against cancer, since it proliferates much more than normal skin cells?
    • Tested against several cancer lines and normal cells with BrdU
      • fluorescent tag similar to thymine, shows DNA synthesis
    • 6-HAP prevented cancer lines from incorporating it (and thus making DNA)
      • But didn't prevent normal cells
  • Why the selectiveness? Mediated by mARCs
    • Mitochondrial amidoxime reducing components – convert stuff like 6-HAP to normal bases
    • More activity in normal cells than cancer
    • When inhibited in normal, reduced resistance to 6-HAP to be more like cancer cells
  • Still, important to ensure 6-HAP doesn't interfere with DNA; could cause mutations
    • Tested with a couple mutagenesis tests, in mouse cells and bacteria
    • But found no mutagenic activity
  • Then actually tested in a live context - in mice with tumors
    • In healthy mice, 6-HAP alone didn't show toxicity even at max dose for 2 weeks injected
    • So then gave to mice inoculated with melanoma cell line to induce tumors
    • Despite aggressive tumors, size suppressed by >60%
  • So molecule works, but what about bacteria that make it?
    • Induced tumors on mouse skin with UV+carcinogen
    • And colonized mouse skin with S. epidermidis, either producing 6-HAP or not
    • Producers had fewer tumors, non-producers had normal number
  • Finally looked in human microbiome datasets, found 6-HAP producers common in humans
  • Summary: Healthy skin bacteria produce compound with antitumor properties, could help prevent skin cancer
  • Applications and implications: Maybe new treatment for cancer
    • Or basis for developing one
  • Useful for research too, when selectively inhibiting DNA synthesis is desired
  • Clarifications if necessary: Seems like resistance could evolve fairly easily
    • Seems already present in healthy cells, in enzymes that degrade 6-HAP
    • So just need for cancer not to inactivate enzymes; not so hard?
  • What do I think: Shows importance of healthy microbiota, even on skin
    • Some evidence that disruptions increase risk of cancer, at least in gut
    • This anticancer molecule production could contribute to effect
    • In addition to immune modulation
    • And maybe disruption of other microbes that increase risks
  • Need to understand better
Last modified on Sunday, 19 August 2018 21:29
Jesse Noar

Jesse Noar is microbiologist with a PhD from North Carolina State University and Bachelor's from Cornell. Most of his research has focused on the amazing abilities and potential uses of bacteria, especially those found in soil. Jesse hosts the BacterioFiles podcast highlighting the most interesting recent microbiology research on all kinds of different microbes, part of the ASM family of podcasts. Learn more at asm.org/bacteriofiles or at www.bacteriofiles.com.

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