ICB Team Identifies Broad Spectrum Antimicrobial that Bacterial Pathogens Can’t Resist
Photo Credit: Ryan Allen and Peter Allen, Second Bay Studios
Antimicrobial resistance (AMR) is one of the most serious global public health threats in this century, according to the World Health Organization, attributing to 1.27 million deaths annually with the highest burden in low- and middle-income countries.
Of particular concern are CDC urgent/WHO critical priority pathogens that are resistant to all—or nearly all—available antibiotics. Despite the imminent public health threat, few promising drug candidates are currently in the clinical pipeline due to the high costs of drug development and the risk that a new antibiotic becomes ineffective due to bacterial resistance.
Two ICB researchers, Professors Michael Mahan and David Low with Professor Chuck Samuel, all of the Molecular, Cellular and Developmental Biology (MCDB) department at UCSB and their team have identified a compound, COE2-2hexyl, that displayed broad-spectrum antibacterial activity and did not evoke bacterial resistance. This compound cured mice infected with clinical bacterial isolates derived from patients with refractory bacteremia. The drug works by disrupting many bacterial functions simultaneously—which may explain how it killed every pathogen tested and why a low level of bacterial resistance was observed after prolonged drug exposure.
The study was just published in the Lancet’s eBioMedicine, A Broad-spectrum Synthetic Antibiotic that does not Evoke Bacterial Resistance, which was the result of an ICB Advanced Scientific Research project.
The team had discovered and developed a novel class of synthetic compounds—conjugated oligoelectrolytes (COEs)—which are highly efficacious against diverse multidrug-resistant (MDR) pathogens, including infections that are virtually untreatable with current antimicrobials. COEs have no structural relationship to any known antibiotic, and bacterial resistance to COEs ranks among the lowest level of any compound tested.
The ease of molecular design, synthesis and modular nature of COEs offer many advantages over conventional antimicrobials, making synthesis simple, scalable and affordable. These COE features enable the construction of a spectrum of compounds with the potential for development as a new versatile therapy for an imminent global health crisis.
Additional drug safety and efficacy studies will need to be conducted to fully understand the clinical benefits and risks before the drug can be used in clinical practice.
