Cell wall Inhibitor


Most penicillins (e.g., penicillin G or benzylpenicillin) are derivatives of 6-aminopenicillanic acid and differ from one another with respect to the side chain attached to the amino group. The most crucial feature of the molecule is the B-lactam ring, which is essential for bioactivity.

Many penicillin resistant bacteria produce penicillinases (also called beta-lactamases), enzymes that inactivate the antibiotic by hydrolyzing a bond in the beta-lactam ring.

The structure of the penicillins resembles the terminal D-alanyl-D-alanine found on the peptide side chain of the peptidoglycan subunit. It is thought that this structural similarity blocks the enzyme catalyzing the transpeptidation reaction that forms the peptidoglycan cross-links. Thus formation of a complete cell wall is blocked, leading to osmotic lysis. This mechanism is consistent with the observation that penicillins act only on growing bacteria that are synthesizing new peptidoglycan.
However, the mechanism of penicillin action is actually more complex.
Penicillins also bind to several periplasmic proteins (penicillin-binding proteins, or PBPs) and may also destroy bacteria by activating their own autolytic enzymes. Penicillin may also stimulate proteins called bacterial holins to form holes or lesions in the plasma membrane, leading directly to membrane leakage and cell death. Penicillins differ from each other in several ways.

The two naturally occurring penicillins, penicillin G and penicillin V, are narrow-spectrum drugs. Penicillin G is effective against bacteria that cause gonorrhea and some cases of meningitis (the Gram-negative Neisseria gonorrhea and N. meningitis, respectively), as well as Gram-positive pathogens such as streptococci and staphylococci.

Penicillin G must be administered by injection (parenterally) because it is destroyed by stomach acid. Penicillin V is similar to penicillin G in spectrum of activity but can be given orally because it is more resistant to stomach acid. The semisynthetic penicillins have a broader spectrum of activity. Ampicillin can be administered orally and is effective against Gram-negative bacteria such as Haemophilus (middle-ear infections), Salmonella (gastroenteritis), and Shigella (dysentery). Carbenicillin and ticarcillin are potent against Pseudomonas and Proteus (wound and respiratory infections). An increasing number of bacteria have become resistant to natural penicillins and many of the semisynthetic analogues.

Physicians sometimes prescribe specific semisynthetic penicillins that are not destroyed by beta-lactamases to combat antibiotic-resistant pathogens. These include methicillin, nafcillin, and oxacillin. However, this practice has been confounded by the emergence of methicillin-resistant bacteria.

Although penicillins are the least toxic of the antibiotics, about 1 to 5% of the adults in the United States develop allergies to them. Occasionally, a person will die of a violent allergic reactions.


Cephalosporins are a family of antibiotics originally isolated in 1948 from the fungus Cephalosporium. They contain a beta-lactam structure that is very similar to that of the penicillins. As might be expected from their structural similarities to penicillins, cephalosporins also inhibit the transpeptidation reaction during peptidoglycan synthesis. They are broad-spectrum drugs frequently given to patients with penicillin allergies; however, about 10% of patients allergic to penicillin are also allergic to cephalosporins.

Vancomycin and Teicoplanin

Vancomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces orientalis. It is a cup-shaped molecule composed of a peptide linked to a disaccharide. The peptide portion blocks the transpeptidation reaction by binding specifically to the D-alanyl-D-alanine terminal sequence on the pentapeptide portion of peptidoglycan.

The antibiotic is bactericidal for the Gram-positive bacteria Staphylococcus and some members of the genera Clostridium (gangrene), Bacillus (food poisoning), Streptococcus (“strep” throat), and Enterococcus (urinary tract infections). It is given both orally and intravenously, and has been particularly important in the treatment of antibiotic-resistant staphylococcal and enterococcal infections.

However, vancomycin-resistant strains of Enterococcus have become widespread, and cases of resistant Staphylococcus aureus have appeared. In these microbes, resistance is conferred when bacteria change the terminal D-alanine to either D-lactate or a D-serine residue, thus altering the target of the antibiotic. Vancomycin resistance poses a serious public health threat: vancomycin has been considered the “drug of last resort” in cases of antibiotic-resistant S. aureus.

Teicoplanin, another glycopeptide antibiotic, is produced by Actinoplanes teichomyceticus. It is similar in structure and mechanism of action to vancomycin but has fewer side effects. It is active against staphylococci, enterococci, streptococci, clostridia, Listeria, and many Gram-positive pathogens.


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