Antimicrobial Agents & Resistance

Natural Biosensor Can Detect Antibiotics Produced by Microbes

 

Researchers at North Carolina State University led by Gavin Williams have drafted the protein MphR to act as a biosensor and help them finds new antibiotics called macrolides, small molecules that can have antibiotic, antifungal, or anticancer effects.  Because macrolides are only produced in small amounts, the team is also trying to find a way to engineer microbes to produce macrolides in large numbers.

“Our ultimate goal is to engineer microbes to make new versions of these antibiotics for our use, which will drastically reduce the amount of time and money necessary for new drug testing and development,” said Williams.  “In order to do that, we first need to be able to detect…antibiotic molecules of interest.”

MphR is a naturally occurring molecular switch in microbes that turns on a resistance mechanism when it senses antibiotics produced by neighboring, predatory microbes.  The researchers created a large library of MphR protein variants and screened them for the ability to switch on a green fluorescent protein when they were in the presence of a macrolide.  They tested the variants using erythromycin, a macrolide found in soil bacteria and which MphR already recognizes. Some of the MphR variants could detect macrolides ten times better than others, even macrolides like tylosin that are not closely related to erythromycin.

Molecular Model of Erythromycin.

“Essentially, we have co-opted and evolved the MphR sensor system, increasing its sensitivity [so we can] recognize the molecules that we’re interested in,” Williams said.  “We know that we can tailor this biosensor [so it can] enable us to screen millions of different strains quickly.  This is the first step toward the high-throughput engineering of antibiotics, where we create vast libraries of genetically modified strains and variants of microbes in order to find the few strains and variants that produce the desired molecule in the desired yield.”

For more information, go to ACS Synthetic Biology; DOI 10.1021/acssynbio.7b00287.

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