Context: Recently, Researchers have identified a new class of antibiotics called ‘Zosurabalpin’ with the potential to tackle a drug-resistant bacterium, Acinetobacter baumannii.

About Zosurabalpin

• Zosurabalpin was previously identified as capable of inhibiting the growth of A. baumannii.

• Scientists identified a tethered macrocyclic peptide (MCP) that selectively kills A. baumannii which was further optimised for efficacy and tolerability, resulting in zosurabalpin.

• It inhibits a crucial process – the transport of lipopolysaccharide (LPS) – by targeting a complex of proteins.

• This complex is vital for transporting LPS to the bacterial surface to form the outer-membrane structure of Gram-negative bacteria.

• Zosurabalpin disrupts LPS transport, leading to an abnormal accumulation of LPS in the cell, ultimately causing the death of the bacterium.

• Additionally, Zosurabalpin significantly reduced bacterial levels in mice with CRAB-induced pneumonia and prevented the death of those with CRAB-related sepsis.

• This complex was essential for transporting LPS to the bacterial surface to create the outer-membrane structure of Gram-negative bacteria. However, the blocking of the LPS transport results in an abnormal build-up of LPS in the cell which kills the bacterium.

• The antibiotic demonstrated efficacy against over 100 clinically tested samples of CRAB in the laboratory.

About CRAB

• CRAB is classified as a priority 1 critical pathogen by the World Health Organization, along with two other drug-resistant bacteria – Pseudomonas aeruginosa and Enterobacteriaceae.

• Crab is a significant cause of infection in hospitals, particularly in people who are on ventilators.

• While it is not an aggressive pathogen it is resistant to multiple different antibiotics, making it very difficult to treat.

• Development of new treatments against this bacterium has been extremely challenging because it is very adept at keeping antibiotics from getting past its outer cell layer.

Threat from Antibiotic-resistant

• Antibiotic-resistant infections, especially those caused by Gram-negative bacteria, pose an urgent threat to human health.

• These bacteria 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 the immune system.