Discovery of coordinately regulated pathways that provide innate protection against interbacterial antagonism

Author:

Ting See-Yeun1,LaCourse Kaitlyn D1,Ledvina Hannah E1,Zhang Rutan2,Radey Matthew C1,Kulasekara Hemantha D1,Somavanshi Rahul1,Bertolli Savannah K1,Gallagher Larry A1,Kim Jennifer1,Penewit Kelsi M3,Salipante Stephen J3,Xu Libin2ORCID,Peterson S Brook1ORCID,Mougous Joseph D145ORCID

Affiliation:

1. Department of Microbiology, University of Washington School of Medicine

2. Department of Medicinal Chemistry, University of Washington School of Pharmacy

3. Department of Laboratory Medicine and Pathology, University of Washington School of Medicine

4. Department of Biochemistry, University of Washington School of Medicine

5. Howard Hughes Medical Institute, University of Washington

Abstract

Bacterial survival is fraught with antagonism, including that deriving from viruses and competing bacterial cells. It is now appreciated that bacteria mount complex antiviral responses; however, whether a coordinated defense against bacterial threats is undertaken is not well understood. Previously, we showed that Pseudomonas aeruginosa possess a danger-sensing pathway that is a critical fitness determinant during competition against other bacteria. Here, we conducted genome-wide screens in P. aeruginosa that reveal three conserved and widespread interbacterial antagonism resistance clusters (arc1-3). We find that although arc1-3 are coordinately activated by the Gac/Rsm danger-sensing system, they function independently and provide idiosyncratic defense capabilities, distinguishing them from general stress response pathways. Our findings demonstrate that Arc3 family proteins provide specific protection against phospholipase toxins by preventing the accumulation of lysophospholipids in a manner distinct from previously characterized membrane repair systems. These findings liken the response of P. aeruginosa to bacterial threats to that of eukaryotic innate immunity, wherein threat detection leads to the activation of specialized defense systems.

Funder

National Institutes of Health

Cystic Fibrosis Foundation

Howard Hughes Medical Institute

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference58 articles.

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