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A new study published in Nature has identified a potential Achilles heel in the protective layers surrounding Gram-negative bacteria that could aid in the development of next-generation antibiotics.

Clusters of the essential protein BamA in the outer membrane of the bacterium Escherichia coli © Dr Gideon Mamou
Clusters of the essential protein BamA in the outer membrane of the bacterium Escherichia coli

The study, carried out jointly by Professor Waldemar Vollmer and Dr Federico Corona at Newcastle University, alongside Professor Colin Kleanthous and Dr Gideon Mamou in the Department of Biochemistry at the University of Oxford, shows that Gram-negative bacteria depend on the cell wall to synchronise building of the outer membrane.

The World Health Organization (WHO) has declared Antimicrobial Resistance (AMR) one of the top 10 global public health threats. Some bacteria have already become resistant to all known antibiotics. Particularly problematic are multidrug resistant Gram-negative bacteria such as Escherichia coliPseudomonas aeruginosa and Klebsiella pneumoniae that cause pneumonias and sepsis. Their outer membrane resides beyond the cell wall and excludes many classes of antibiotics that would otherwise target it.

The research reveals that the cell wall, which is composed of a tough material known as peptidoglycan, exerts surprising control over where new proteins are introduced into the outer membrane by an essential biogenesis protein known as BamA. This helps bacteria coordinate these layers, which is crucial for the way they grow.

Read the full story on the Department of Biochemistry website

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