OCT 02, 2015 7:08 PM PDT

New Antibiotic Targets Riboswitch

WRITTEN BY: Kerry Evans
A research team at Merck (accidentally) uncovered a new antibacterial target - a riboswitch important for riboflavin (vitamin B2) biosynthesis.  The team screened nearly 60,000 small molecules for antibacterial activity and found one that suppressed bacterial growth by binding directly to the riboswitch.
  
Structure of a typical riboswitch
A riboswitch is a segment of messenger RNA (mRNA) that typically interacts with an effector molecule to regulate translation of the mRNA.  Riboswitches contain two functional parts, the aptamer, which interacts with the effector molecule, and the expression platform, which directly regulates gene expression.  Many riboswitches regulate the production of metabolites such as riboflavin, glutamine, glycine, and lysine.  The riboflavin riboswitch binds flavin mononucleotide, which is synthesized from riboflavin, to downregulate the riboflavin synthesis pathway.  

The Merck team, led by John Howe, set out to find a drug that would kill bacteria by blocking riboflavin synthesis.  This pathway is unique to bacteria, so there would be no off-target effects on humans.  To find their drug, they screened nearly 60,000 small molecules for the ability to kill E. coli in the absence of riboflavin.  According to Howe, “if the effect of that antibacterial was suppressed by riboflavin … then we had a good chance that the small molecule … was targeting the riboflavin pathway”.

The group confirmed that ribocil effectively killed E. coli cells in culture, then tested its activity in a mouse model.  After altering its structure to increase its activity, they showed that ribocil decreased the bacterial load in mice.  

One (relatively significant) shortcoming is that ribocil was only effective at killing a weakened strain of E. coli.  Wild type cells were able to expel the drug, making them resistant.  Despite this drawback, however, the Merck team has shown that riboswitches are viable antibiotic targets.

Sources: Nature, The Scientist, Wikipedia
 
About the Author
  • Kerry received a doctorate in microbiology from the University of Arkansas for Medical Sciences.
You May Also Like
AUG 18, 2020
Microbiology
The Science of Pesto
AUG 18, 2020
The Science of Pesto
  The word pesto comes from the Genovese word pestâ (pestare in Italian) which means “to pound” o ...
AUG 28, 2020
Microbiology
As Buildings Reopen After Lockdowns, They Find Legionella
AUG 28, 2020
As Buildings Reopen After Lockdowns, They Find Legionella
Several schools and even buildings at the Centers for Disease Control and Prevention (CDC) have identified Legionella ba ...
OCT 12, 2020
Microbiology
Researchers May Have Found a Way to Cure Rotavirus Infections
OCT 12, 2020
Researchers May Have Found a Way to Cure Rotavirus Infections
Rotaviruses are very contagious. They are the most common cause of diarrhea in children and are estimated to cause about ...
OCT 29, 2020
Cell & Molecular Biology
How Does the Immune System Handle the Microbiome?
OCT 29, 2020
How Does the Immune System Handle the Microbiome?
The human body plays host to trillions of microbes, and many of them live in our gastrointestinal tract; these microorga ...
NOV 22, 2020
Microbiology
The Mechanisms Underlying Rotavirus Infections are Revealed
NOV 22, 2020
The Mechanisms Underlying Rotavirus Infections are Revealed
Rotaviruses are the biggest reason why young children get diarrhea. It's estimated that 215,000 kids die every year from ...
NOV 23, 2020
Microbiology
Drug Resistance in Tuberculosis Involves a Unique Mechanism
NOV 23, 2020
Drug Resistance in Tuberculosis Involves a Unique Mechanism
The pathogenic bacterium that causes tuberculosis, Mycobacterium tuberculosis, does not multiply quickly, so researchers ...
Loading Comments...