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.