New class of antibiotics tackles ‘untreatable’ bacteria with virtually no resistance

A team of scientists at the University of California, Santa Barbara, have developed a new class of antibiotics to treat mice infected with a bacterium classified as virtually untreatable, and have detected no resistance to treatment, they say. Discovery paves the way to begin tackling growing challenges. antimicrobial resistance (AMR) is a growing public health threat that disproportionately affects the health of people in low- and middle-income countries.

the study, published on wednesday in the journal eBio Medicinestated that the drug compound COE2-2hexyl works through the simultaneous disruption of many bacterial functions. It explains why.

Douglas Heithoff, senior scientist at the University of California, Santa Barbara Collaborative Biotechnology Institute and lead author of the study, said: “Most drugs fail at this stage of development and never make it to the clinic.”

The discovery of this compound came from an unlikely and unrelated project. The project is a U.S. Army-funded project led by Guillermo his Bazan of the University of California, Santa Barbara, to develop new ways to charge mobile phones in the field. Bazan’s group designed a compound that harnesses the energy of bacteria to create a “microbial” battery. After development, the team realized that perhaps the compound they created could be tested as a potential antibiotic.

New antibiotics have unique mechanisms of action. Unlike other drugs used to treat bacterial infections that target specific reproductive functions, COE2-2hexyl targets many functions simultaneously. “This drug appears to affect bacterial membranes, which disrupts the functions of multiple bacteria,” said co-project leader and professor of molecular, cellular, and developmental biology at the University of California, Santa Barbara. One David Low said: “This may explain the broad-spectrum antibacterial activity and low level of bacterial resistance.”

Some of the membrane-associated functions that the new antibiotics have impacted include septation, motility, ATP synthesis, respiration, and membrane permeability to small molecules, which may influence the evolution of bacterial cell viability and drug resistance. “Disruption of these bacterial properties can occur through alterations of key protein-protein or protein-lipid membrane interfaces, which destabilize membranes and induce bacterial cell lysis.” “It is a different mechanism of action than other membrane-disrupting antibacterial agents or surfactants,” the researchers wrote. This is a different mechanism of action than many membrane-disrupting antimicrobials or surfactants, which destabilize membranes in order to induce bacterial cell lysis.”

To settle on tested compounds, the team synthesized 15 chemical variants of conjugated oligoelectrolytes (COEs). COE2-2hexyl was identified as the most promising as it exhibits broad-spectrum antibacterial activity.

Two aspects that make this compound very promising as an antibacterial agent are that bacteria do not appear to be resistant to treatment and that it is easy to synthesize.

“The ease of molecular design, synthesis, and modular nature of COEs offer many advantages over conventional antimicrobial agents, making synthesis simple, scalable, and affordable,” the research team concluded. I was. “These COE capabilities will enable the construction of a wide variety of compounds that have the potential to be developed as novel, versatile treatments for the impending global health crisis.”

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