Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery.

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Cho H, Uehara T, Bernhardt TG

Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery.

Cell. 2014 Dec 4;159(6):1300-11. doi: 10.1016/j.cell.2014.11.017.

PubMed ID

25480295 [ View in PubMed

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Abstract

Penicillin and related beta-lactams comprise one of our oldest and most widely used antibiotic therapies. These drugs have long been known to target enzymes called penicillin-binding proteins (PBPs) that build the bacterial cell wall. Investigating the downstream consequences of target inhibition and how they contribute to the lethal action of these important drugs, we demonstrate that beta-lactams do more than just inhibit the PBPs as is commonly believed. Rather, they induce a toxic malfunctioning of their target biosynthetic machinery involving a futile cycle of cell wall synthesis and degradation, thereby depleting cellular resources and bolstering their killing activity. Characterization of this mode of action additionally revealed a quality control function for enzymes that cleave bonds in the cell wall matrix. The results thus provide insight into the mechanism of cell wall assembly and suggest how best to interfere with the process for future antibiotic development.

DrugBank Data that Cites this Article

Drugs

Bacampicillin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bacampicillin	Penicillin-binding protein (Protein Group)	Protein group	Gram positive and gram negative bacteria	Yes	Inhibitor	Details