Thread by @Dr_TJRicks

Now that you know what the top 5 antibiotic resistant infections are, let’s keep it goin and talk about the different classes of antibiotics and what they do

I’ll start by listing the top 10 generic antibiotics below 👇🏾

#DrTJWrites

https://twitter.com/dr_tjricks/status/1552447217721802752

I’ll start by listing them below, then organizing them by structural class

1) amoxicillin
2) doxycycline
3) cephalexin
4) ciprofloxacin
5) clindamycin
6) metronidazole
7) azithromycin
8) sulfamethoxazole + trimethoprim
9) amoxicillin + clavulanate
10) levofloxacin

Many of these are in different structural classes so let’s talk about those

A) Penicillins/β-lactams (amoxicillin)

These antibiotics are called β-lactams because of their structure

A lactam is an organic structure that is cyclic (fused ring) and contains nitrogen.

They’re specifically called β-lactams because the β tells you were the nitrogen is in relation to the carbon attached to the double bonded oxygen (carbonyl carbon).

It is 2 carbons away from the carbonyl carbon. α is 1. β is 2 in this naming convention.

β-lactams work by inhibiting cell wall synthesis in bacteria.

The cell wall is an essential structure in bacteria and when it is disrupted, the bacteria dies. The drug works because it mimics the the amino acid blueprint used to make the cell wall and it gets incorporated.

So the bacteria tries to use the drug to make its cell wall because it looks like a common cell wall precursor.

It gets incorporated and disrupts wall integrity causing the bacterial contents to leak out and the bacteria dies.

Now notice 9) includes clavulanate. Why?

Clavulanate is a β-lactamase inhibitor

Well what is β-lactamase?

The suffix -ase in biochemistry indicates an enzyme. An enzyme is a protein that causes reactions to happen faster.

β-lactamase is an enzyme that can break β-lactam rings. Where would you encounter this?

In penicillin resistant bacteria

These bacteria have created a enzyme that busts these drugs open at the lactam so they cannot disrupt cell wall integrity

Clavulanate inhibits this enzyme so that your penicillin of choice can still work.

There are 4 different antibiotic classes that contain β-lactam rings

The difference in the 4 is the structure surrounding the β-lactam ring

These different structures slightly modulate the activity of the drug typically in

*metabolic half-life
*substrate binding

B) Cephalosporins (Cephalexin)

This same cartoon that we used above also contains cephalosporins. They also contain β-lactam rings so they work the same way as penicillins.

C) Tetracyclines (doxycycline)

Tetracyclines are exactly what they say they are

Tetra-4
Cycline-circle/cycle

Tetracyclines are organic molecules with 4 fused rings together. They are lettered a-d.

Tetracyclines are not bactericidal, which means they don’t kill bacteria, they inhibit their growth.

The growth inhibition comes from disrupting protein synthesis by binding to parts of the ribosome (protein coder) that are read to make these proteins.

D) Fluoroquinolones (ciprofloxacin)

Fluoroquinolones are simply quinolones that have fluorine attached to them.

They are synthetic derivatives of naturally occurring compounds called quinolines, anti-malaria compounds originally found in cinchona bark.

These compounds work by destroying bacterial DNA so they cannot replicate.

This chart also illustrates how changing things around the ring changes the activity of the molecule.

This is fairly standard for drugs and follows a concept called SAR, structure activity relationship

E) Lincomycin (clindamycin)

Lincomycins are amino acid (blue circle) and sugar (red circle) conjugates that have a similar mode of action to tetracyclines, inhibiting growth via disrupted protein synthesis.

Lincomycins are interesting because they actually come from bacteria, specifically Streptomyces lincolnensis.

When bacteria are competing for resources and space, some will send out molecules that will help by eliminating the competition.

F) Nitroimidazoles (metronidazole)

Nitroimidazoles are derivatives of the common organic molecule imidazole that contain a nitro group (NO2). These drugs are bactericidal and thought to work again by destroying bacterial DNA preventing replication.

G) Macrolides (azithromycin)

Macrolides are huge biomolecules that are typically a 8+ membered lactone ring fused to two other molecules, typically sugars

Below are the naming conventions and the common structures.

These molecules were originally found in Actinomycetales

Here again we have an agent produced by bacteria to kill other competing bacteria

Survival of the fittest extends to the microscopic scale

H) Sulfonamides (sulfamethoxazole)

Sulfonamides combine two classic organic chemistry motifs

The sulfone (sulfur double bonded to two separate oxygens)

The amine (NH2)

They also are not limited to being antibiotics as you can see in the cartoon below

Sulfonamides work by inhibiting folic acid synthesis through direct competition with PABA, para-amino benzoic acid.

The only difference is the sulfonamide (left) replaces the carboxylic acid. (Right)

Man that took a lot longer than I thought 😂😂

These are your common antibiotics, what they look like, and how they work. Next time we’ll look at how scientists are trying to replace these drugs and curb drug resistance. If you enjoyed this thread, Rt the 1st tweet 🙏🏾

https://twitter.com/Dr_TJRicks/status/1552712706297315328

And if you wanna know why this topic is important, go here 👇🏾

https://twitter.com/dr_tjricks/status/1552434121141526530