Roche Study Finds Novel Antibiotic Targets Drug-Resistant Bacteria

Researchers have made a significant breakthrough in the fight against antibiotic-resistant bacteria, with a particular focus on Acinetobacter baumannii, a bacterium causing severe and often fatal infections resistant to numerous existing antibiotics. This pathogen is known for its impact on the lungs, urinary tract, and blood, showing resilience against carbapenems, a broad-spectrum class of antibiotics.

Thriving in medical environments like hospitals and nursing homes, CRAB poses an increased risk to individuals with catheters, those on ventilators, or those recovering from surgery with open wounds. Due to its robust resistance, the US Food and Drug Administration has refrained from approving a new antibiotic class for CRAB for over half a century.

While CRAB represents only 2% of hospital infections in the US, it is more prevalent in the Middle East as well as Asia, contributing to infections in intensive care units globally by close to 20%.

In a collaborative effort involving Harvard University and Hoffmann-La Roche, scientists have developed a promising antibiotic named zosurabalpin. This unique compound, belonging to its own chemical class, utilizes an innovative mechanism to effectively eliminate Acinetobacter baumannii. Dr. Kenneth Bradley, a key researcher, emphasizes the inventive approach of both the compound and its bacteria-killing mechanism.

The challenge lies in treating Acinetobacter baumannii, a Gram-negative bacterium protected by inner and outer membranes, making antibiotic penetration challenging. The researchers aimed to identify and refine a molecule capable of traversing these dual membranes to target and eliminate the bacteria.

Zosurabalpin, derived from screening 45,000 small antibiotic molecules, inhibits Acinetobacter baumannii growth by disrupting the movement of lipopolysaccharides, causing their accumulation within bacterial cells and eventual cell demise. 

Demonstrating efficacy against over 100 CRAB clinical samples, zosurabalpin exhibited noteworthy reductions in bacterial levels in rodents with CRAB-induced pneumonia. 

Currently undergoing phase 1 clinical trials to evaluate safety, tolerability, and pharmacology in humans, zosurabalpin holds promise in addressing antibiotic-resistant infections. Despite this progress, the persistent global threat of antimicrobial resistance remains due to a lack of effective treatments, as cautioned by Dr. Michael Lobritz, emphasizing the imperative need for ongoing research.

In 2019, approximately 1.3 million people worldwide succumbed directly to antimicrobial resistance, surpassing deaths from other serious illnesses such as malaria. In the US alone, over 2.8 million antimicrobial-resistant infections are reported annually, which lead to more than 30,00 deaths. 

While the clinical application of zosurabalpin is years away, its development is hailed as a promising breakthrough by Dr. César de la Fuente from the University of Pennsylvania. 

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