Original subtitles

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.