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The discovery pipeline for novel antibiotics runs dry, while antimicrobial resistances increase, causing 1.3 million deaths per year globally. Even in the European Economic Area with generally intact health care, more than 35,000 people die per year with numbers expected to rise. Especially certain pathogenic Gram-negative bacteria are to blame. Optimized versions of the innovative natural product class of darobactins acting selectively at a novel target on the bacterial outer membrane may provide novel treatment options. [ABSTRACT FROM AUTHOR]

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β-barrel transmembrane proteins are present in outer membranes of bacteria and organelles of eukaryotic cells like mitochondria and chloroplasts. After their synthesis in the cytosol, bacterial outer membrane proteins are translocated in unfolded form across the cytoplasmic membrane into the periplasm. Chaperones assist their transport to the β-barrel assembly machinery BAM of the outer membrane. Biophysical studies on outer membrane protein A indicated a concerted folding and insertion mechanism into lipid bilayers for which the activation energy is lowered by the BAM-complex. [ABSTRACT FROM AUTHOR]