Human variation impacting MCOLN2 restricts Salmonella Typhi replication by magnesium deprivation.

Autor:	Gibbs KD; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710, USA., Wang L; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710, USA., Yang Z; Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany., Anderson CE; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710, USA., Bourgeois JS; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710, USA.; University Program in Genetics and Genomics, Duke University, Durham, NC 27710, USA., Cao Y; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710, USA., Gaggioli MR; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710, USA., Biel M; Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany., Puertollano R; Cell and Developmental Biology Center, National Heart, Lung, & Blood Institute, NIH, Bethesda, MD 20892, USA., Chen CC; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan., Ko DC; Department of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, NC 27710, USA.; University Program in Genetics and Genomics, Duke University, Durham, NC 27710, USA.; Division of Infectious Diseases, Department of Medicine, School of Medicine, Duke University, Durham, NC 27710, USA.
Jazyk:	angličtina
Zdroj:	Cell genomics [Cell Genom] 2023 Apr 04; Vol. 3 (5), pp. 100290. Date of Electronic Publication: 2023 Apr 04 (Print Publication: 2023).
DOI:	10.1016/j.xgen.2023.100290
Abstrakt:	Human genetic diversity can reveal critical factors in host-pathogen interactions. This is especially useful for human-restricted pathogens like Salmonella enterica serovar Typhi ( S. Typhi), the cause of typhoid fever. One key defense during bacterial infection is nutritional immunity: host cells attempt to restrict bacterial replication by denying bacteria access to key nutrients or supplying toxic metabolites. Here, a cellular genome-wide association study of intracellular replication by S . Typhi in nearly a thousand cell lines from around the world-and extensive follow-up using intracellular S. Typhi transcriptomics and manipulation of magnesium availability-demonstrates that the divalent cation channel mucolipin-2 (MCOLN2 or TRPML2) restricts S. Typhi intracellular replication through magnesium deprivation. Mg 2+ currents, conducted through MCOLN2 and out of endolysosomes, were measured directly using patch-clamping of the endolysosomal membrane. Our results reveal Mg 2+ limitation as a key component of nutritional immunity against S. Typhi and as a source of variable host resistance. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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