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Antimicrobial resistance (AMR): a novel antibiotic Zosurabalpin (RG6006) shows promise in pre-clinical trials

Antibiotic resistance particularly by Gram-negative bacteria has nearly created a crisis like situation. The novel antibiotic Zosurabalpin (RG6006) shows promises. It has been found to be effective against drug-resistant, Gram-negative bacteria CRAB in pre-clinical studies.   

Antimicrobial resistance (AMR), driven mainly by the misuse and overuse of antimicrobials, is one of top public health risk.  

Infections by Gram-negative bacteria are particularly concerning. It is not easy for most of antibiotics to cross both inner and outer membranes present in this category of bacteria to enter the bacterial cells to show bactericidal actions. Also, Gram-negative bacteria have accumulated disproportionately high degree of antibiotic resistance.  

Acinetobacter baumannii is a Gram-negative bacterium. Infection by one of its strains called ‘carbapenem-resistant Acinetobacter baumannii’ (CRAB) is hard to treat using available antibiotics. There is an urgent need for an effective antibiotic against CARB as mortality rate is high (about 40%-60%) which attributed largely to lack of an effective antibiotic. A progress towards this goal has been reported.  

Scientists have identified a novel class of antibiotics namely, tethered macrocyclic peptides (MCPs) which are active against the Gram –ve bacteria A. baumannii including CARB by blocking transport of bacterial lipopolysaccharide from the inner membrane to the outer membrane.  

Zosurabalpin (RG6006) is an antibiotic candidate belonging to ‘tethered macrocyclic peptides (MCPs)’ class. In pre-clinical trials involving in vitro studies and in vivo studies on animal models, Zosurabalpin has been found to be effective against drug-resistant isolates of ‘carbapenem-resistant Acinetobacter baumannii’ (CRAB) from different regions. It successfully overcame antibiotic-resistance mechanism of CARB suggesting Zosurabalpin has potential.  

Hence, human clinical trials have been initiated to check for safety and efficacy Zosurabalpin in treating invasive infections caused by CRAB.  

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References:  

  1. Zampaloni, C., Mattei, P., Bleicher, K. et al. A novel antibiotic class targeting the lipopolysaccharide transporter. Nature (2024). https://doi.org/10.1038/s41586-023-06873-0 
  2. Hawser S., et al 2023. Activity of the Novel Antibiotic Zosurabalpin (RG6006) against Clinical Acinetobacter Isolates from China, Open Forum Infectious Diseases, Volume 10, Issue Supplement_2, December 2023, ofad500.1754, https://doi.org/10.1093/ofid/ofad500.1754  

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Umesh Prasad
Umesh Prasad
Science journalist | Founder editor, Scientific European magazine

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