{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Sharifian Gh M"],"funding":["NEI NIH HHS","NCI NIH HHS"],"pubmed_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 <i>P. aeruginosa</i> 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 of the inner membrane transporters FeoB and PotH, respectively, to suppress both ferrous iron and polyamine uptake. This broadly shuts down transcription of many biofilm-associated genes, including ferrous iron-dependent TauD and ExbB1. The mechanism is innate to the surface of the eye and is enhanced by synergistic coupling with thrombin peptide GKY20. This is the first example of an inhibitor of multiple bacterial transporters."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.03.01.582947"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10925246"],"repository":["biostudies-literature"],"pubmed_title":["Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death."],"pmcid":["PMC10925246"],"funding_grant_id":["R01 EY032956","R01 EY026171","P30 CA044579"],"pubmed_authors":["Gahlmann A","Pires MM","Sharifian Gh M","Ongwae GM","Ryan M","Achimovich A","Belfort G","Venter H","Sorci M","Liang B","Zaid TS","Harris TE","Pier GB","Laurie GW","Norouzi F","Lemke M","Gadjeva M"],"additional_accession":[]},"is_claimable":false,"name":"Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.","description":"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 <i>P. aeruginosa</i> 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 of the inner membrane transporters FeoB and PotH, respectively, to suppress both ferrous iron and polyamine uptake. This broadly shuts down transcription of many biofilm-associated genes, including ferrous iron-dependent TauD and ExbB1. The mechanism is innate to the surface of the eye and is enhanced by synergistic coupling with thrombin peptide GKY20. This is the first example of an inhibitor of multiple bacterial transporters.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-04-08T16:08:29.337Z","creation":"2025-04-06T17:28:22.48Z"},"accession":"S-EPMC10925246","cross_references":{"pubmed":["38464199"],"doi":["10.1101/2024.03.01.582947"]}}