Beta-lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam ring in their molecular structures.
A common example is penicillins
Penicillins have a core structure of 6-aminopenicillanic acid
, but can differ in their R group, which determines the stability and antimicrobial spectrum of the penicillin.
Naturally occurs as Benzylpenicillin
– is not effective orally) and Phenoxymethylpenicillin
– is effective orally) – both are sensitive to breakdown by enzymes called β-lactamases and both are poorly active against Gram negative bacteria.
In 1959 chemists at Beechams isolated 6-aminopenicillanic acid (6-APA) i.e. the β-lactam structure minus the R sidechain
(The sidechain can also be cleaved by an enzyme called penicillin amidase)
6-APA is used as the building block for numerous ‘semisynthetic’ penicillin analogues that differ only in their sidechain – this imparts various properties:
- e.g. Methicillin – is relatively resistant to β-lactamases
- Ampicillin & Amoxycillin – are more active against Gram negatives (except Pseudomonas spp.)
- Carbenicillin – is active against Gram negatives incl. Pseudomonas
All β-lactam antibiotics inhibit the final stage of peptidoglycan synthesis in the bacterial cell wall, thereby causing them to burst.
- In a newly formed peptidoglycan sugar chain, the amino acid chain on the N-acetylmuramic acid has two D-Alanines at the end (dipeptide), one of which is cleaved allowing linking (transpeptidation). This is facilitated by transpeptidase.
- β-lactam antibiotics are structurally similar to D-Ala-D-Ala dipeptides, and so react with traspeptidases to block activity (Penicillin binds transpeptidase and occupies the active site, preventing its function).
By doing this, β-lactams therefore interfere with cell wall synthesis in growing cells.
Cells which are not fast growing, or have already grown will therefore be resistant to β-lactams since they only prevent growth, and do not degrade already formed peptidoglycan.
Some bacteria become resistant because they produce β-lactamase.
- Beta-lactamases are enzymes produced by some bacteria that provide resistance to β-Lactam antibiotics like penicillins, cephamycins, and carbapenems
- Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure.
- These antibiotics all have a common element in their molecular structure: a four-atom ring known as a β-Lactam.
- Through hydrolysis, the lactamase enzyme breaks the β-Lactam ring open, deactivating the molecule's antibacterial properties.