DRAM1 confers resistance to Salmonella infection.
| Title: | DRAM1 confers resistance to Salmonella infection. |
|---|---|
| Authors: | Masud S; Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; Xie J; Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; Grijmans BJM; Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; van der Kooij S; Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; Zhang R; Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; Prajsnar TK; Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.; Department of Evolutionary Immunology, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-382 Krakow, Poland.; Meijer AH; Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. |
| Source: | Autophagy reports [Autophagy Rep] 2023 Aug 24; Vol. 2 (1), pp. 2242715. Date of Electronic Publication: 2023 Aug 24 (Print Publication: 2023). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Taylor and Francis Country of Publication: United States NLM ID: 9918383885906676 Publication Model: eCollection Cited Medium: Internet ISSN: 2769-4127 (Electronic) Linking ISSN: 27694127 NLM ISO Abbreviation: Autophagy Rep Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [Philadelphia, Pennsylvania] : Taylor and Francis, [2022]- |
| Abstract: | DRAM1 is an infection inducible autophagy modulator, previously shown to promote autophagic and lysosomal defense responses against the intracellular pathogen Mycobacterium marinum. However, its possible role in other anti-bacterial autophagic mechanisms remains unknown. Recently, LC3-associated phagocytosis (LAP) has emerged as autophagy-related mechanism that targets bacteria directly in phagosomes. Our previous work established LAP as the main autophagic mechanism by which macrophages restrict growth of Salmonella Typhimurium in a systemically infected zebrafish host. We therefore employed this infection model to investigate the possible role of Dram1 in LAP. Morpholino knockdown or CRISPR/Cas9-mediated mutation of Dram1 led to reduced host survival and increased bacterial burden during S. Typhimurium infection. In contrast, overexpression of dram1 by mRNA injection curtailed Salmonella replication and reduced mortality of the infected host. During the early response to infection, GFP-Lc3-Salmonella associations were reduced in dram1 knockdown or mutant embryos, and increased by dram1 overexpression. Since LAP is known to require the activity of the phagosomal NADPH oxidase, we used a Salmonella biosensor strain to detect bacterial exposure to reactive oxygen species (ROS) and found that the ROS response was largely abolished with deficiency of dram1, while it was increased with dram1 overexpression. Corroborating these results in a mammalian model, the LC3 and ROS responses to Salmonella were similarly reduced or increased by knockdown or overexpression of Dram1, respectively, in murine RAW264.7 macrophages. Together, these results demonstrate the host protective role of Dram1/DRAM1 during S. Typhimurium infection and suggest a functional link between Dram1/DRAM1 and the induction of LAP. Abbreviations: ATG8: Autophagy related protein 8; ATG16: Autophagy related protein 16; CFU: colony-forming unit; DRAM1: DNA damage regulated autophagy modulator gene 1; dpf: days post fertilization; GFP: green fluorescent protein; hpi: hours post infection; LAP: LC3 associated phagocytosis; LC3, microtubule-associated protein 1 light chain 3; NADPH: Nicotinamide dinucleotide phosphate; p53: Tumor suppressor protein 53: ROS; reactive oxygen species; S. Typhimurium: Salmonella enterica serovar Typhimurium; TIPTP: 2(tetrahydroindazolyl) phenoxy-N-(thiadiazolyl)propenamide 2; UVRAG: UV radiation resistance associated protein.; (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.) |
| References: | Front Immunol. 2019 Apr 17;10:832. (PMID: 31110502); Oncol Lett. 2018 Feb;15(2):1435-1440. (PMID: 29399189); Sci Rep. 2020 Mar 12;10(1):4570. (PMID: 32165681); Cell. 2019 Jul 25;178(3):552-566.e20. (PMID: 31327526); Oncol Lett. 2018 Aug;16(2):2427-2433. (PMID: 30013633); Cell Death Dis. 2020 Apr 24;11(4):277. (PMID: 32332700); Mol Cell. 2019 Oct 3;76(1):163-176.e8. (PMID: 31492633); Front Cell Infect Microbiol. 2019 Aug 02;9:279. (PMID: 31428591); Immunity. 2010 Mar 26;32(3):329-41. (PMID: 20206555); Curr Opin Microbiol. 2013 Jun;16(3):339-48. (PMID: 23623150); Cell. 2006 Jul 14;126(1):121-34. (PMID: 16839881); Autophagy. 2019 May;15(5):796-812. (PMID: 30676840); Autophagy. 2021 Apr;17(4):888-902. (PMID: 32174246); PLoS One. 2011 Mar 11;6(3):e17852. (PMID: 21412437); Curr Opin Immunol. 2018 Dec;55:54-61. (PMID: 30286399); Cell Death Dis. 2015 Jan 29;6:e1624. (PMID: 25633293); PLoS One. 2013 May 17;8(5):e63245. (PMID: 23696801); Nat Cell Biol. 2011 Feb;13(2):132-41. (PMID: 21258367); Front Cell Infect Microbiol. 2022 Jan 03;11:809121. (PMID: 35047422); Nat Cell Biol. 2015 Jul;17(7):893-906. (PMID: 26098576); Cell Microbiol. 2003 Sep;5(9):601-11. (PMID: 12925130); Front Immunol. 2021 May 11;12:618569. (PMID: 34046029); Autophagy. 2012 Jan;8(1):18-28. (PMID: 22082963); J Exp Med. 2003 Nov 3;198(9):1361-8. (PMID: 14597736); Dev Cell. 2004 Apr;6(4):463-77. (PMID: 15068787); Mol Immunol. 2010 Nov-Dec;48(1-3):179-90. (PMID: 20851470); Cells. 2023 Mar 07;12(6):. (PMID: 36980169); PLoS Pathog. 2013;9(5):e1003328. (PMID: 23658518); Cell Host Microbe. 2014 Jan 15;15(1):72-83. (PMID: 24439899); Genes Dev. 2007 Nov 15;21(22):2861-73. (PMID: 18006683); Cell Microbiol. 2006 May;8(5):719-27. (PMID: 16611222); Mol Cell. 2021 May 6;81(9):2031-2040.e8. (PMID: 33909989); Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6226-31. (PMID: 19339495); Autophagy. 2014;10(12):2389-91. (PMID: 25484076); Nat Rev Immunol. 2013 Oct;13(10):722-37. (PMID: 24064518); Nature. 2007 Dec 20;450(7173):1253-7. (PMID: 18097414); Nat Commun. 2021 Mar 8;12(1):1508. (PMID: 33686057); Autophagy. 2017 Feb;13(2):423-441. (PMID: 27764573); Cell Death Dis. 2020 Sep 17;11(9):768. (PMID: 32943616); Autophagy. 2022 Oct;18(10):2267-2269. (PMID: 35811564); Oncogene. 2013 Feb 7;32(6):699-712. (PMID: 22525272); Cell Host Microbe. 2014 Jun 11;15(6):753-67. (PMID: 24922577); Cell Microbiol. 2013 Mar;15(3):395-402. (PMID: 23121192); Autophagy. 2021 Sep;17(9):2642-2644. (PMID: 34251968); Mol Biol Cell. 2004 Mar;15(3):1101-11. (PMID: 14699058); Nat Rev Microbiol. 2014 Feb;12(2):101-14. (PMID: 24384599); Curr Opin Immunol. 2019 Oct;60:81-90. (PMID: 31247378); Sci Rep. 2017 Mar 20;7:44795. (PMID: 28317932); Antioxidants (Basel). 2021 Feb 19;10(2):. (PMID: 33669824); Dev Comp Immunol. 2014 Dec;47(2):223-33. (PMID: 25086293); J Cell Biol. 2022 Jun 6;221(6):. (PMID: 35511089) |
| Contributed Indexing: | Keywords: DRAM1; LC3-associated phagocytosis; ROS; Salmonella; innate immunity; macrophages |
| Entry Date(s): | Date Created: 20250915 Date Completed: 20250915 Latest Revision: 20250917 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12427088 |
| DOI: | 10.1080/27694127.2023.2242715 |
| PMID: | 40950712 |
| Database: | MEDLINE |
Journal Article