title: A self-lysis pathway that enhances the virulence of a pathogenic bacterium.
abstract: In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. Although this is lethal to the individual cell in which it occurs, we find it benefits the population as a whole during infection of a mammalian host. Thus, host and pathogen each may use PCD as a survival-promoting strategy. We suggest that activation of the Alp cell lysis pathway is a disease-enhancing response to bacterial DNA damage inflicted by the host immune system.
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Kirsty A
authors.identifier: http://orcid.org/0000-0003-2150-1771
authors.initials: KA
authors.lastname: McFarland
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Hanover, NH 03755;
authors.forename: Emily L
authors.initials: EL
authors.lastname: Dolben
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195.
authors.forename: Michele
authors.initials: M
authors.lastname: LeRoux
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Tracy K
authors.initials: TK
authors.lastname: Kambara
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Ramsey
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195;
authors.forename: Robin L
authors.initials: RL
authors.lastname: Kirkpatrick
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195;
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Mougous
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Hanover, NH 03755;
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Hogan
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115; simon.dove@childrens.harvard.edu.
authors.forename: Simon L
authors.initials: SL
authors.lastname: Dove
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001433:Bacteriolysis / Q000235:genetics*; D015153:Blotting, Western; D015964:Gene Expression Regulation, Bacterial; D008297:Male; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000235:genetics; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D009876:Operon / Q000235:genetics; D011552:Pseudomonas Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics*; D059008:Time-Lapse Imaging; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors
keywords: Pseudomonas aeruginosa; cell lysis; essential regulator; lung colonization; programmed cell death