A new antibiotic identified to target a drug-resistant bacterium

News Excerpt:

Researchers have identified a new class of antibiotics, Zosurabalpin, with the potential to tackle a drug-resistant bacterium, Acinetobacter baumannii.

About the bacteria ‘Acinetobacter baumannii’:

  • Antibiotic-resistant infections pose an urgent threat to human health particularly those caused by a large group of bacteria known as Gram-negative bacteria, which are protected by an outer shell containing a substance called lipopolysaccharide (LPS).
    • LPS allows bacteria to live in harsh environments, and it also allows them to evade attack by our immune system.
  • Acinetobacter baumannii is a Gram-negative bacteria, meaning it is protected by inner and outer membranes, making it difficult to treat. 
  • It can cause serious infections in the lungs, urinary tract and blood, according to the US Centers for Disease Control and Prevention. 
  • It’s resistant to a class of broad-spectrum antibiotics called carbapenems.
  • Carbapenem-resistant Acinetobacter baumannii, also known as CRAB, was at the top of the World Health Organization’s list of antibiotic-resistant “priority pathogens” in 2017.
  • CRAB is classified as a priority 1 critical pathogen by the World Health Organization, alongside two other drug-resistant forms of bacteria: Pseudomonas aeruginosa and Enterobacteriaceae.
  • CRAB accounts for about 2% of infections found in US hospitals. 
    • It’s more common in Asia and the Middle East and causes up to 20% of infections in intensive care units worldwide.

About Research on Antibiotic Zosurabalpin:

  • The goal of the research was to identify and fine-tune a molecule that could cross the double membranes under LPS and kill the bacteria ‘CRAB’.
  • The researchers began developing zosurabalpin by examining about 45,000 small antibiotic molecules called tethered macrocyclic peptides and identifying those that could inhibit the growth of different types of bacteria. 
  • After years of improving the potency and safety of fewer compounds, the researchers landed on one modified molecule.

Results during research: 

  • Zosurabalpin inhibits the growth of Acinetobacter baumannii by preventing the movement of large molecules called lipopolysaccharides to the outer membrane, where they’re needed to maintain the membrane’s integrity
    • This causes the molecules to accumulate inside the bacterial cell. 
    • Levels inside the cell become so toxic that the cell itself dies.
  • Zosurabalpin considerably reduced levels of bacteria in mice with Crab-induced pneumonia and prevented the death of those with Crab-related sepsis.
  • Drug discovery that targets harmful Gram-negative bacteria is a long-standing challenge owing to difficulties in getting molecules to cross the bacterial membranes to reach targets in the cytoplasm.
  • Gram-positive bacteria is typically less harmful and less resistant to antibiotics than Gram-negative bacteria.

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