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Dead Bacteria

There are a goodly number of medicinal agents that remain useful for treating bacterial infections, even despite the specter of antibiotic resistance. One of the reasons such drugs still do their job is that they collectively target a variety of vulnerable functions of a creature’s biochemistry, and thereby make it more difficult to develop a resistance mechanism to every possible toxin we might toss at the bugs.

The three broadest drug classes are inhibitors of protein synthesis, cell wall synthesis, and DNA synthesis. Disruption of any of these vital functions is bound to make the bacterium in question very unhappy. And if bacteria are unhappy enough, they simply give up and die. Voila, no more infection.

The paradigm of multiple targets for drug action recently became more complex. A Boston-based research collaboration showed that although common antibiotics have established cellular targets, inhibition of those targets is not the proximal cause of cell expiration. Instead, virtually all classes of antibiotics initiate a sequence of events that starts with target inhibition (of cell wall synthesis, for example), followed by elevation of reactive oxygen (especially the hydroxyl radical), which oxides the DNA base guanine, which leads to double stranded breaks in the DNA, which results in death of the cell.

Why should we care how complex the events are that lead a bacterium to its grave? At one level, as long as our infection is gone we aren’t all that worried about why it happened, just relieved to feel better. But two powerful trends are disquieting: new drug discovery has dramatically slowed in recent decades, and emergent drug resistance continues its relentless pace. Happily, and perhaps just in the nick of time, these new results have the potential to enhance the effectiveness of current therapies, conceivably by potentiating reactive oxygen production, or by inhibiting cellular DNA repair.

Even better would be avoiding promiscuous use of antibiotics in animals and humans, but solutions to those problems lie more in the political realm than the scientific.

Related:
Book Review: Examining a Panacea [Chemical Heritage]
Bacteriamageddon [Periodic Tabloid]
Drug Resistant Bacteria Found in 4-Million-Year-Old Cave [National Geographic]

Posted In: History

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