Mind the Membrane
Asystole

Candida albicans, tipping my hat,
A little yeast neighbour, quite pleased with that.
With a nucleus tucked in my house of my own,
I thought my foundations would leave me alone.

Eukaryotic, with rooms inside,
A membrane and a wall on the outer side.
Chitin and glucans help that wall stay strong,
Ergosterol in the membrane keeps things moving along.
Some fungi grow as branching hyphal threads,
Some live as yeasts with rounded little heads.
Humans study the differences, finding a clue—
Which part of our house can a medicine get through?

Wall outside, membrane within,
That's where the trouble begins.
Echinocandins weaken the wall;
Azoles make ergosterol fall.
Polyenes bind it, and ions can flee—
My own little house is betraying me.

Lanosterol fourteen-alpha-demethylase—
Azoles block that step in the sterol-making race.
Less ergosterol, altered sterols in place,
Membrane function has a problem to face.
Amphotericin B binds ergosterol tight,
Membrane permeability changes overnight.
Ions can leak from a susceptible cell;
A familiar little room doesn't work so well.

Wall outside, membrane within—
Mind the membrane; trouble's getting in.

An echinocandin reaches glucan synthase,
Blocks new wall material from joining the place.
One-three-beta-D-glucan production falls;
Now there's less support for my growing walls.
Human cells have no such wall to build,
A difference the drug designers have revealed.
Still, species and drug have to be matched with care—
Every fungus won't answer the same way there.

Flucytosine enters; enzymes change the view,
Cytosine deaminase makes five-F-U.
Active metabolites disrupt R-N-A,
And block thymidylate synthase, slowing D-N-A.
A different target inside my little home—
The walls and membrane aren't standing alone.

Wall outside, membrane within,
That's where the trouble begins.
Echinocandins weaken the wall;
Azoles make ergosterol fall.
Polyenes bind it, and ions can flee—
My own little house is betraying me.

Candida albicans, holding my hat:
"Mind the membrane. Remember that."