The Discovery of Antibiotics

The Discovery of Antibiotics


Hi. I’m Phillip, and I’d like to talk to you
today about sequencing antibiotics. So before we get into antibiotic
sequencing I just want to give you a short discussion of the discovery of
antibiotics because it’s something I feel like is pretty
cool. It’s cool because it goes against,
probably, what you’ve learned about science in
science class. There are some lessons here that are a
little bit different. So, to give you the story, penicillin was discovered in 1928. It was the first antibiotic to be
discovered. It was discovered by Alexander Fleming,
and he went on vacation. And he was known for keeping a messy lab,
and when he comes back after a few weeks. He notices that the cultures of bacteria that he had been studying had been contaminated with a mold called
penicillium. And that when this mold had contaminated the bacteria, it had
killed the bacteria everywhere that they had
contaminated them. And so he said, okay. Well, now we’ve got something that can
kill bacteria. What do we do with it? So this led to a 15 year process from the
discovery of the drug to designing the drug and
getting it useful so that it would be mass produced
for D-Day, 15 years later, when it was able to save thousands
of wounded soldier’s lives. Antibiotics are so relevant, though, to
modern medicine that I think that we have to step back and ask
ourselves, would we all even be here. I know that I had something called Scarlet
Fever when I was young twice, and that’s caused by this
bacterium, Streptococcus pyogenes. This is a disease that carried a substantial mortality rate in past
centuries. But it’s just, you take the
antibiotics and you get better now, right? The issue with that is that maybe bacteria
is starting to fight back a little bit. We’re now starting to see the rise of
antibiotic resistant bacteria, such as MRSA or Methicillin-resistant
staphylococcus aureus, that resist most antibiotics that are
known. And this is troubling.
So, for example, here’s an antibiotic on a petri dish and the MRSA has spread regardless of the
presence of the antibiotic. So let’s define what antibiotic really
means, and I’m using it loosely to be a substance that goes in and kills bacteria.
Where do these come from? Well, they occur naturally, just like the penicillium mold that Alexander
Fleming discovered. A mold is a type of fungus, and fungi have evolved over time to have these
antibiotics so that they can kill bacteria. They’re also produced by other bacteria in order to kill bacteria. One example would be a bacterium called
Bacillus Brevis. And that’s the bacterium that we’re going
to study today. It produces an antibiotic known as
Tyrocidine B1. So, what is Tyrocidine B1 on a molecular
level? It’s a “mini protein” called a peptide. So, this peptide is really just a short
string of amino acids. There are 20 commonly occurring amino
acids. And amino acids are represented either in
a single letter alphabet. So, the peptide here is VKLF, etc. Or sometimes, there’s a three-letter
abbreviation That’s shown here. and this amino acid sequence
is valine, lysine, leucine, and so on. So we now have a number of questions that
we ask about antibiotics now that we know a
little bit about them. The first question would be, well they’re
peptides, proteins occur everywhere, so what makes
these antibiotics special? Second, we would ask, then, how is it that the bacterium produces these
antibiotics? And then, thirdly, what the central
question is going to be of this lecture, is, how is it that we, as
bioinformaticians sequence antibiotics. How is it that we know what the sequence of amino acids in
Tyrocidine B1 really is. And so that question is what we’re going
to talk about today, centrally. Although we’re going to discuss these
other questions as well, because we’re interested in the
biology.

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