NOVEMBER 7TH, 2023POSTED BY SARAH AVERY-DUKE

This transport mechanism gets internalized in the bacterium and brings in a molecule that causes what we’ve described as a berserker reaction—a programmed death response,” says Timothy Haystead. “It wipes out the bacteria—sterilizes the culture with a single dose of light.” (Credit: Getty Images)

Using a technique that has shown promise in targeting cancer tumors, researchers have found a way to deploy a molecular “warhead” that can annihilate the bacterium that causes Lyme disease.

Tested in cell cultures using the Borrelia burgdoferi bacterium, the approach holds the potential to target not only bacteria, but also fungi such as yeast and viruses.

The findings appear in the journal Cell Chemical Biology.

“This transport mechanism gets internalized in the bacterium and brings in a molecule that causes what we’ve described as a berserker reaction—a programmed death response,” says Timothy Haystead, professor in the pharmacology and cancer biology department at Duke University. “It wipes out the bacteria—sterilizes the culture with a single dose of light. And then when you look at what occurs with electron microscopy, you see the collapse of the chromosome.”

Haystead and colleagues used a molecular facilitator called high-temperature protein G (HtpG), which is involved in protecting cells that are undergoing heat stress. This family of proteins has been the focus of drug development programs for possible cancer therapies.

Studies of this protein as an antimicrobial have also been encouraging, but the researchers’ work appears to be the first to tether an HtpG inhibitor to a drug that enhances sensitivity to light.

The researchers found that the HtpG inhibitor, armed with the photosensitive drug, was rapidly absorbed into the cells of the Lyme bacteria. When hit with light, the bacteria’s cells went into disarray and ultimately collapsed, killing them.

“Our findings point to a new, alternate antibiotic development strategy, whereby one can exploit a potentially vast number of previously unexplored druggable areas within bacteria to deliver cellular toxins,” Haystead says.

The Steven and Alexander Cohen Foundation and Bay Area Lyme Foundation funded the work.

Source: Duke University

Original Study DOI: 10.1016/j.chembiol.2023.10.004