How Do Antibiotics Work?

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How do antibiotics work?Drew Smith:

Antibiotics have been around for a long time now, and we know which bacterial proteins they attack. ß-lactams like amoxicillin inhibit the enzyme that crosslinks peptidoglycans in bacterial cell walls. Fluoroquinolones like ciprofloxacin bind DNA topoisomerases and prevent them from coiling and uncoiling bacterial chromosomes. But so what? How does blocking these processes actually kill bacterial cells?

It turns out that we really don’t know a lot about how antibiotics actually kill bacteria, although we are beginning to get some clues.

One of these clues is that some antibiotics require bacterial protein synthesis in order to be effective: inhibition of protein synthesis reduces the lethality of ß-lactams, for instance. Simply blocking cell wall synthesis does not lead to rapid and complete killing of bacteria—something more is required.

Further research shows that antibiotics induce bacterial stress responses, and it is these responses, rather than the immediate activity of the antibiotics, which lead to cell death. In fact, a unified theory of antibiotic-induced cell death is beginning to emerge in which several classes of antibiotics work through a common mechanism.

Essentially, the stress response of cells to antibiotics causes disregulation of the carefully controlled membrane electrical potential. All cells generate chemical energy by pumping positively charged protons out of the cell, leaving an excess of negatively charged electrons within. The electrical potential created by this mechanism is enormous, as Nick Lane has pointed out; at the cellular scale, it is equivalent to a bolt of lightning.

Normally this power is used to turn a turbine-like molecular assembly (ATP synthase) that converts electrical energy into chemical energy. But when the flow of power is disrupted, a storm of highly reactive electrons is let loose in the cell, where they destroy everything—proteins, DNA, RNA.


We don’t yet understand all the steps that make this happen. That blue box in the figure which says “Metabolic Feedback” is really a black box. But this research should surely lead to new strategies for designing antibiotics and suppressing the evolution of antibiotic resistance.

This post originally appeared on Quora. Click here to view.