OSU Biochemistry and Molecular Biology

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ANTIBIOTICS, RESISTANCE, AND THE TRANSLATIONAL MACHINERY IN BACTERIA        null

Antibiotics are some of our most powerful and valued drugs, virtually eradicating previously dreaded diseases such as scarlet fever, tuberculosis, and bubonic plague. Ironically, only a few new antibiotics have been introduced since the 1960s. A crisis looms on the horizon with old antibiotics losing their effectiveness due to the rise of multidrug-resistant bacteria, chronic infections, and immune-compromised patients. Resistance arises from two primary sources: from bacteria harboring mobile resistance genes that can be spread to other cells; and from ‘persister cells’, which are dormant variants of regular bacteria that are highly tolerant to antibiotics. The rise in resistance is exacerbated by our ubiquitous use of antibiotics in everything from medicine to agriculture. Furthermore, antibiotics indiscriminately attack harmful and helpful bacteria in our gastrointestinal tracts and societies.  

Antibiotics from natural sources (plants, fungi, and other bacteria) commonly target bacterial ribosomes, which translate mRNAs into proteins. This translational machinery is also a source for acquiring resistance to antibiotics. The highly conserved nature of this machinery facilitates our broad use of antibiotics, yet it also promotes resistance in bacterial populations. Translation and antibiotics are inextricably connected to bacterial physiology, growth and multiplication. Yet there is a significant lack of information about how ribosome-targeting antibiotics alter bacterial physiology.

To begin to fill this void, my lab is investigating how antibiotics perturb the translational machinery in bacterial cells. Using novel methodology, we are purifying the full translational machinery from both harmful and helpful bacteria. We are quantitatively assessing the components of this machinery and other putative factors connecting it to bacterial physiology. We are comparing the effects of antibiotics on the composition and dynamics of the translational machinery. These studies will reveal how antibiotics that target the ribosome dismantle bacterial physiology, leading to bacterial death. These insights will be a critical prerequisite for the development of new more effective and specific antibiotics. And they prepare us for the new more deadly drug-resistant bacteria that will most assuredly arise in the future.
 

Superbugs.jpg

Overuse of antibiotics has spawned resistant bacteria (“superbugs”).
Credit: Artwork by Cassio Lynm

 

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