All language subtitles for 1.1 - Penicillin

It was only less than 100 years ago when
Alexander Fleming accidentally

discovered penicillin because he left
his lab bench all gross and moldy. But

thousands of years, ancient people were
already putting moldy bread and steaming

piles of soil on wounds to treat
infection.

And billions of years before that,
bacteria themselves invented the first

antibiotics. Yeah, the story of
antibiotics started a long time ago.

In a primordial world far, far away.

Cue John Williams.

Okay, so that was Azusa March.

Not exactly the Imperial March.

But you know what? Just stick with me,
and you're going to go on an amazing and

mostly copyright infringement -free
adventure.

Let's start this tour of antibiotics
with penicillin. Though she's better

as Princess Ellen, rebel spy against the
Agalactia Empire.

Notice the lightsaber she's holding
looks like a purple pencil.

This pencil is one of our recurring
symbols for penicillin in Sketchy Micro.

So for those of you who've seen the
symbol already, it means you're a

veteran, likely a microbiology genius
among your peers.

For those of you new to Sketchy, a lot
of the symbols used here will

recapitulate many of the lessons from
Sketchy Micro, and we're going to go

a few of them shortly.

Okay, so the penicillins share
properties of their pharmacology and

action with cephalosporins, monobactams,
carbapenems, beta -lactamase

inhibitors. All of them are beta -lactam
compounds, which means that they have a

four -membered beta -lactam ring.

just with different constituents
attached.

We'll always represent a beta -lactam
antibiotic with a ringed planet like

one. See that beta -lactam ring?

Penicillins, like all beta -lactams,
interfere with the transpeptidation

reaction of bacterial cell wall
synthesis.

So because they act on the cell wall,
think of them working well against that

thick gram -positive peptidoglycan wall.

In general, penicillins have greatest
activity against gram -positive

like Staph and Strep, represented here
by these purple, coxoid space stations

clusters and chains, kind of like Staph
and Strep colonies.

You see that armored space station being
built? The one with enough firepower to

destroy an entire planet?

That's the Death Caucus.

Its structure will remind us of the
bacterial cell wall.

composed of a complex cross -linked
polymer of polypeptides and

peptidoglycan.

Specifically, we're going to highlight
the peptide structure that terminates

with D -alanil -D -alanine. Notice the
repeating D -ala -D -ala architectural

motif.

Penicillin binding proteins, or PBPs,
remove the terminal alanine in the

of forming cross -links between
peptides.

So, PVPs are, in essence, construction
workers, represented here by these space

workers building the wall of the Death
Caucus, part of the planetary building

project, of course.

Penicillins, as well as other beta
-lactam antibiotics, inhibit this

transpeptidation reaction by covalently
binding the PVPs, hence the name

penicillin binding proteins.

So penicillins work by halting
peptidoglycan synthesis in actively

cells, and the cell dies.

That's bactericidal.

So we're in a period of civil war, of
course, and ships have come to rescue

Princess Ellen.

While they're probably aiming for the
conveniently exposed thermal exhaust

they're taking out the PVPs.

Notice the shapes of the wings.

These V -winged ships.

represents penicillin V, which is the
oral form of penicillin, meaning it's

stable. So to remind you of that, here's
a big acid yellow nebula behind them.

Penicillin V is indicated only in minor
infections because of its poor

bioavailability, four times a day
dosing, and narrow spectrum.

Penicillin G is the IV form of
penicillin, represented here by Princess

who's being held captive by the A
-Galactia Empire's evil agents.

Look at that side bun.

So G -shaped.

She's struggling to escape from a rope
made of ivy tied around her neck, and

ivy is reminding you that penicillin G
is administered IV.

Benzathine salts of penicillin G can
also be given as intramuscular

So we've mentioned that penicillin has
good activity against gram -positive

organisms.

Let's go over some of its key clinical
uses, many of which are for

infections.

Oral penicillin V is an agent of choice
for group A streptococcal pharyngitis,

or strep throat.

And notice that the V -winged pilots are
wearing red bandanas around their

necks, as a symbol of loyalty to the
rebel cause.

Let this red bandana around the throat,
now and in future stories, remind you of

streptococcal pharyngitis.

But we all know that a sore throat can
lead to a broken heart, and if we look

out the window behind her, we can see
that her home planet, Syningham, has

already been destroyed by the Death
Caucus.

Notice the heart shape combined with
fire, to remind you that penicillin V,

G, are treatments for rheumatic fever.

As we look on in horror, take a look at
the emperor of palpitations himself,

Emperor Viridans.

Come to the dock.

His dark green robe is there to remind
you of strep viridans, and his bicuspid

-shaped hat represents the left -sided
endocarditis caused by strep viridans

strepovis, both of which can be treated
with penicillin G.

One more strep infection to mention, and
that's strep agalactiae, or group B

strep. Always remember Group B for
babies.

And outside on the space dock is a
galactic baby.

Heir to the Agalactia throne, he's
attached to an umbilical cord -esque

line to remind you that penicillin G is
given intrapartum for Group B strep

prophylaxis.

Let's move on from strep infections and
take a look at what else is going on out

on the space dock.

One thing to remember is that penicillin
is used to treat Actinomyces israeli, a

gram -positive rod that grows in chains,
represented here by this purple and rod

-shaped cargo transporter.

Notice how the cargo is labeled with the
Empire's official star emblem, which

looks suspiciously like the Israeli
flag.

At the head of the train, the driver has
fallen off the space cargo vehicle, and

notice he has some road rash.

His spacesuit is perforated, and he's
likely susceptible to a Clostridium

perfringis infection, which leads to
gangrene, which can be treated with

penicillins. He was probably swerving
out of the way of that stray space dog

on the loading dock.

Pasturella infections are commonly
caused by dog bites and treated with

penicillin, as well as other more broad
-spectrum beta -lactams such as

ampicillin and piperacillin.

Take a close look at the astronaut being
chased by the dog. Red gloves, boots,

just like the palms and soles rash of
secondary syphilis, caused by the

spirochete Treponema pallidum.

A single dose of benzathine penicillin G
provides low but persistent serum

levels of penicillin and is standard
therapy for primary, secondary, or early

latent syphilis.

Because it's a spirochete, we've even
thrown in a spiral galaxy right behind

him. Alright, one more clinical use to
mention.

Notice that most of the microbes we've
covered so far are gram -positive, but

there's one important gram -negative
one, which we'll depict in red.

Meningococcal meningitis, caused by
Neisseria meningitidis, a gram -negative

diplococcus, is treated well with
penicillin G, if the isolate is proven

penicillin -susceptible.

So IV penicillin can effectively
penetrate the CNS during active

And our red -helmeted bouncy hunter,
donning a red meningitis mohawk, will

represent this diplococcus.

Notice the red gram -negative
diplococzoid pair of rocket boosters

him.

In the midst of this intergalactic civil
war, we'd expect some resistance.

The most common mechanism of resistance
is the production of beta -lactamases,

such as those produced by Staph aureus.

To show this, we have a beta -lactamase
trooper shooting down one of Princess

Ellen's V -winged ships, displaying a
very threatening crossed -out beta

on his armor.

In later sketches, we'll talk about how
antibiotics deal with these beta

-lactamases, which are often expressed
by plasmid genes.

So notice the ring structure on the beta
-lactamase guard's gun, which is meant

to look like circular plasmid DNA.

Okay, we've been through a lot, I know.

And to finish off this beta -lactam
space opera, I'll mention some adverse

reactions caused by penicillin, though
they are generally well tolerated.

The most serious adverse effects are due
to a type 1 or IgE -mediated

hypersensitivity, which can result in
anaphylaxis.

To show this, we have a red -faced pilot
shutting his swollen eyes as he heads

into a dangerous asteroid field.

Notice the long IgE missiles on the side
of his ship.

While up to 10 % of patients may have a
reported penicillin allergy, as many as

90 % of these individuals will likely
have negative skin testing and tolerate

penicillin without an adverse reaction.

Also remember that 10 % number for the
degree of cross -reactivity with

cephalosporins, though this number is
also over -reported.

In clinical practice, cephalosporins are
more likely to cause an adverse

reaction in patients with a penicillin
allergy.

if they have had positive skin testing
in the past to penicillin, or if their

previous allergic reaction to penicillin
consisted of definite IgE -mediated

clinical features and occurred within 10
years.

Why is there an asteroid field, you ask?

Sadly, it's what remains of Princess
Ellen's destroyed planet.

And notice that our pilot is firing
shorter IgG -shaped missiles onto the

asteroid field that look suspiciously
like... red blood cells.

These exploding asteroids will represent
the autoimmune hemolytic anemia that

can result from penicillin
administration.

This results in a positive direct Coombs
test, which just means it's due to

antibodies against penicillin binding to
the surface of red blood cells.

If we look into the distance, we can see
one more important adverse effect.

It's a kidney -shaped nebula, here to
represent interstitial nephritis.

This is caused by mononuclear cells
entering the interstitium of the kidney,

on histology, these little blue cells
kind of look like these blue star

throughout the interstitium of this
kidney nebula.

Beautiful, isn't it?

Well, there you have it.

Let's break down this space opera into a
few important points.

Penicillin is a beta -lactam antibiotic
with activity against gram -positive

organisms, halting peptidoglycan
synthesis, leading to cell death.

It's used for strep infections,
actinomyces, pasturella, and syphilis.

out for that hypersensitivity and
subsequent cross -reactivity with

cephalosporins. The next stop on our
tour, penicillin's resistance to staph

-lactamases.