Antibiotics & AMR Part 2: Cell-Wall Synthesis & Beta-Lactams

This flashcard set covers the classification of antibiotics, the structure and synthesis of bacterial peptidoglycan, and the specific mechanisms by which beta-lactams and other wall-active drugs inhibit bacterial growth.

Selective toxicity

The ability of a drug to attack specific bacterial processes (the target site) that human cells largely do not have.

Spectrum of activity

The range of bacteria a drug works against; a narrow-spectrum drug hits few groups, while a broad-spectrum drug hits many.

Bactericidal

A descriptor for drugs that kill bacteria outright, such as beta-lactams.

Bacteriostatic

A descriptor for drugs that stop bacteria from multiplying without directly killing them, allowing the immune system to finish the job.

Peptidoglycan

A mesh of sugar chains tied together by short peptides that forms the bacterial cell wall, providing shape and preventing bursting.

NAG and NAM

The two alternating sugars, $N\text{-acetylglucosamine}$ ($NAG$) and $N\text{-acetylmuramic acid}$ ($NAM$), that form the glycan backbone of peptidoglycan.

Transglycosylase

The enzyme activity that joins peptidoglycan monomers sugar-to-sugar into long glycan chains.

Transpeptidase

The enzyme activity that cross-links the peptide side-chains of neighboring glycan chains to provide wall strength; the primary target of beta-lactams.

Osmotic lysis

The bursting of a bacterium due to water rushing in when the cell wall is damaged or insufficiently cross-linked.

mDAP

$\text{meso-diaminopimelic acid}$, which occupies position 3 of the pentapeptide in Gram-negative bacteria and Bacillus, allowing for direct cross-linking.

MurA

A cytoplasmic enzyme inhibited by fosfomycin that is involved in the first step of peptidoglycan synthesis by helping build the $NAM\text{-pentapeptide}$ precursor.

Fosfomycin

A natural broad-spectrum antibiotic that acts as a phosphoenolpyruvate ($PEP$) analogue and inhibits MurA in the cytoplasm.

Cycloserine

An antibiotic that blocks the cytoplasmic formation of the terminal $D\text{-Ala-}D\text{-Ala}$ residues of the pentapeptide.

Undecaprenyl phosphate ($C_{55}$)

The hydrophobic membrane lipid carrier that ferries the hydrophilic $NAM\text{-}NAG\text{-pentapeptide}$ building blocks across the cell membrane.

Bacitracin

An antibiotic that interferes with cell-wall synthesis by blocking the recycling of the $C_{55}$ lipid carrier.

Vancomycin

An antibiotic that binds tightly to the terminal $D\text{-Ala-}D\text{-Ala}$ of the pentapeptide, physically capping it to prevent its addition to the wall or cross-linking.

PBPs (penicillin-binding proteins)

Membrane enzymes, including transpeptidases and carboxypeptidases, that catalyze the final steps of cell-wall assembly and are inhibited by beta-lactams.

Beta-lactam ring

The four-membered ring structure central to penicillins and relatives that mimics the structure of $D\text{-Ala-}D\text{-Ala}$ to irreversibly jam PBPs.

Natural penicillins

Drugs like penicillin G and penicillin V that are primarily effective against Gram-positives and are the choice for streptococcal pharyngitis and syphilis.

Penicillinase

A type of beta-lactamase, often plasmid-borne in $S.\text{ aureus}$, that breaks the beta-lactam ring; produced by over $90\%$ of $S.\text{ aureus}$ strains.

Penicillinase-resistant penicillins

Modified beta-lactams such as methicillin, oxacillin, cloxacillin, and flucloxacillin that withstand breakdown by staphylococcal enzymes.

MRSA (methicillin-resistant Staphylococcus aureus)

Strains that resist nearly all beta-lactams by carrying the $mecA$ gene, which produces a substitute enzyme ($PBP2a$) with very low drug affinity.

PBP2a

An extra penicillin-binding protein with low affinity for beta-lactams that continues building the cell wall in MRSA even when other PBPs are blocked.

Beta-lactamase inhibitors

Molecules like sulbactam and clavulanate that are combined with antibiotics to disable resistance enzymes and protect the partner drug from destruction.