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Promising Antibiotics Target Drug-Resistant Bacteria

— June 25, 2024

New antibiotics, lolamicin and zosurabalpin, show promise against antibiotic-resistant gram-negative bacteria.

The escalating threat of drug-resistant bacteria is not just a health crisis, but a pressing global health emergency. As existing antibiotics lose their effectiveness, medical professionals are left grappling with limited options to combat life-threatening infections. However, a ray of hope emerges from recent research unveiling two potential antibiotic candidates: lolamicin and zosurabalpin.

Lolalicin, developed by researchers at the University of Illinois Urbana-Champaign, targets gram-negative bacteria, a particularly troublesome class due to their double cell wall and the limited options for effective antibiotics. This new drug works by inhibiting the Lol system, a protein transport system that is essential for the survival of gram-negative bacteria but absent in beneficial gut microbes. The Lol system is responsible for transporting lipoproteins, which are crucial for the bacteria’s outer membrane, from the inner to the outer membrane.

In cell culture experiments, lolamicin effectively targeted several drug-resistant strains of E. coli, Klebsiella pneumoniae, and Enterobacter cloacae, with minimal impact on gram-positive bacteria.  Even more promising, lolamicin successfully treated mice with drug-resistant septicemia and pneumonia, with a 100% survival rate in septicemia cases. Importantly, lolamicin treatment avoided gut dysbiosis, a gut microbiome disruption commonly caused by broad-spectrum antibiotics.

Professor Paul Hergenrother, who led the lolamicin research, emphasizes this is a “proof-of-concept” study. Lolalicin, or similar compounds, requires further testing against a wider range of bacteria and detailed toxicity studies. The thoroughness of this process ensures the scientific validity of the findings. Despite these hurdles, lolamicin represents a significant step forward in the fight against gram-negative infections.

Promising Antibiotics Target Drug-Resistant Bacteria
Photo by Polina Tankilevitch from Pexels

Another promising discovery comes from Hoffman-La Roche Pharma. Their research team identified zosurabalpin, a new class of antibiotic targeting carbapenem-resistant Acinetobacter baumannii (CRAB). This drug-resistant bacteria causes serious infections like sepsis and pneumonia with a high mortality rate. The World Health Organization classifies CRAB as a critical threat due to the urgent need for new treatments.

According to the Ineos Oxford Institute for Antimicrobial Research, Zosurabalpin operates by obstructing lipopolysaccharide (LPS) transport across the bacterial cell wall, a novel mechanism that existing antibiotics do not target. This unique approach suggests that zosurabalpin may be unaffected by current resistance mechanisms, potentially making it a potent weapon against CRAB infections. By targeting a different aspect of the bacteria’s structure and function, zosurabalpin could potentially overcome the resistance challenges posed by CRAB.

The research on zosurabalpin is also in its early stages. Further studies are needed to confirm its effectiveness and safety in humans, as well as to understand its potential side effects and interactions with other medications. However, the unique mechanism of action offers significant promise for tackling this highly resistant pathogen. It’s important to note that, like any other new drug, zosurabalpin may have limitations, and its full potential will be determined through rigorous scientific investigation.

These breakthroughs herald a much-needed advancement in the battle against antibiotic resistance. Lolalicin and zosurabalpin introduce novel classes of antibiotics that could potentially surmount the resistance challenges posed by some of the most alarming bacterial strains. Their potential to save lives is a glimmer of hope for the future of effective antibiotic therapy.


New antibiotic lolamicin shows promise in fighting drug-resistant infections

New antibiotic class shows promise against drug-resistant bacteria

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