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Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death

ABSTRACT: Discovering new bacterial signaling pathways offers unique antibiotic strategies. Here, through an unbiased resistance screen of 3,884 gene knockout strains, we uncovered a previously unknown non-lytic bactericidal mechanism that sequentially couples three transporters and downstream transcription to lethally suppress respiration of the highly virulent P. aeruginosa strain PA14 - one of three species on the WHO's 'Priority 1: Critical' list. By targeting outer membrane YaiW, cationic lacritin peptide 'N-104' translocates into the periplasm where it ligates outer loops 4 and 2 respectively of the inner membrane transporters FeoB and PotH to respectively suppress both ferrous iron and polyamine uptake. This broadly shuts down transcription of many biofilm-associated genes, including ferrous iron-dependent TauD and ExB1. The mechanism is innate to the surface of the eye enhanced by synergistic coupling with thrombin peptide GKY20. This is the first example of an inhibitor of multiple bacterial transporters.

ORGANISM(S): Pseudomonas aeruginosa PA14

PROVIDER: GSE253123 | GEO | 2024/01/16

REPOSITORIES: GEO

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