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
FEB 17, 2020
Immunology
FEB 17, 2020
Another HIV vaccine attempt fizzles out
Years of work and over $100 million in study costs have been abandoned after an HIV-vaccine tested in South Africa failed to protect treated individuals ag...
FEB 16, 2020
Microbiology
FEB 16, 2020
Images of Coronavirus Are Released as First Death Outside China is Reported
Previously known as 2019-nCoV, the virus has a new name: SARS-CoV-2, which is the cause of what's being called COVID-19 disease....
FEB 18, 2020
Microbiology
FEB 18, 2020
Newly Found Glycopeptide Antibiotics Kill Bacteria in a New Way
The overuse and misuse of antibiotics and the adaptability of microbes has created a problem that people must solve....
FEB 23, 2020
Cell & Molecular Biology
FEB 23, 2020
A New Class of Bacterial Enzymes is Discovered
Bacterial enzymes can serve many processes, from breaking down pollutants and digesting foods to metabolizing drugs....
MAR 02, 2020
Drug Discovery & Development
MAR 02, 2020
DIY Fecal Transplants Improve Symptoms in 82% of People
Fecal transplants (FMT), the process of putting a healthy person’s fecal matter into another person’s colon, has been approved as a procedure t...
MAR 15, 2020
Microbiology
MAR 15, 2020
A Second Person Has Been Cured of HIV
New research has suggested that after long-term follow-up, HIV is no longer detectable in a patient that was previously HIV-positive....
Loading Comments...