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Printable Handouts
Navigable Slide Index
- Introduction
- Discovery of antimicrobials
- The high-tech platform
- Reviving the Waksman platform
- Uncultured bacteria
- How to grow unculturables
- Colonies growth
- Diffusion chamber vs. Petri dish
- Trap for capturing actinomycetes
- iChip
- iChip placed in soil
- Efficiency of recovery in iChip vs. Petri dish
- Diversity in iChip vs. Petri dish
- From sand to mechanism
- The sand biofilm
- Closer look on sand biofilm
- The basic mechanism of uncultivability
- Growth factors from neighboring species
- Siderophore
- Siderophore specificity in growth induction
- Model for siderophore and unculturable bacteria
- Domestication of uncultured producers
- Increasing domestication of unculturables
- A low-resistance antibiotic
- Biochemical pathway
- Taxonomy tree of Eleftheria terrae
- Teixobactin spectrum
- Teixobactin resistance development
- Specificity of action
- Finding the targets
- Teixobactin: mechanism of action
- Killing of S. aureus by teixobactin
- In vivo efficacy
Topics Covered
- The high-tech & Waksman platforms
- How to grow unculturable bacteria
- Diffusion chamber, Petri dish and iChip comparison
- The sand biofilm
- Siderophores of neighbouring bacteria
- Teixobactin: mechanism and efficacy
Links
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Therapeutic Areas:
Talk Citation
Lewis, K. (2021, November 9). Teixobactin kills pathogens without detectable resistance [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 9, 2024, from https://doi.org/10.69645/EZKA6161.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Kim Lewis has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Update Available
The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.
- Full lecture Duration: 36:00 min
- Update interview Duration: 10:39 min
A selection of talks on Microbiology
Transcript
Please wait while the transcript is being prepared...
0:00
I am Kim Lewis, Professor of Biology
at the Department of Biology at Northeastern University in Boston.
I'm also director of Antimicrobial Discovery Center,
and I will be telling you today about
teixobactin, a new antibiotic that we discovered,
and how teixobactin kills pathogens without detectible resistance.
0:24
So I'd like to place our finding into the general context
of what is happening in the field of antimicrobial discovery,
and I will also spend some time explaining how we got the compound.
So I'll tell you about our discovery platform.
But let me start indeed with where we are with antibiotic discovery.
We once had a golden era of antibiotic discovery.
As you see here from approximately the 40s and through
the 60s, the major classes of antibiotics have been discovered,
and most of them came from mining of soil microorganisms.
That platform was developed by Selman Waksman of Rutgers University
who essentially elaborated on the original finding of
Fleming discovered penicillin.
So Fleming's case, there was a Petri dish with staph bacteria on it
that was left carelessly opened, and a spore of a fungus,
a penicillin fungus settled on that Petri dish,
and Fleming when he came to work the next day,
he discovered that there was a zone of growth inhibition
around the cone of the growing fungus.
So that was the beginning of the discovery of penicillin.
So when Waksman decided to elaborate on that,
he systematically screened soil bacteria,
primarily streptomycetes, that he was working on
for their ability to inhibit growth of bacteria.
An extremely simple method and extremely powerful,
he got a Nobel Prize both for the method and for the discovery of Streptomycin,
the first antibiotic capable of treating tuberculosis.
And then suddenly something happened
in the early '70s.
It looks like somebody turned off our ability to discover new compounds.
The most effort resulted in rediscovery of things like penicillin and streptomycin.
So then it became apparent that the soiled microorganisms
that Waksman and others had been working on
is a very limited resource, only about 1% of microorganisms from
any external environment are going to grow in our Petri dishes.
The rest are uncultured,
so 99% of the enormous diversity on the planet
are uncultured microorganisms.
It's a fascinating paradox.
So then looking back at our timeline,
then there is a gap when nothing is happening, and then
the last decade, a number of new compounds and classes
have been introduced, so it looks like
we are getting back in the game.
That, however, is an illusion.
If you replot this graph not by year of introduction
of compound, but by year of discovery,
what you will notice is that these new discoveries
actually collapse back to the golden era,
these are compounds that were discovered a long time ago,
didn't seem very promising, and were dropped.
And now, we are resuscitating them because we don't have anything better.
So that is where we are.