Undecaprenyl phosphate translocases confer conditional microbial fitness.

Autor: Sit B; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.; Department of Microbiology, Harvard Medical School, Boston, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Srisuknimit V; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.; Department of Microbiology, Harvard Medical School, Boston, MA, USA.; Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand., Bueno E; Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden., Zingl FG; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.; Department of Microbiology, Harvard Medical School, Boston, MA, USA., Hullahalli K; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.; Department of Microbiology, Harvard Medical School, Boston, MA, USA., Cava F; Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden. felipe.cava@umu.se., Waldor MK; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA. mwaldor@research.bwh.harvard.edu.; Department of Microbiology, Harvard Medical School, Boston, MA, USA. mwaldor@research.bwh.harvard.edu.; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. mwaldor@research.bwh.harvard.edu.; Howard Hughes Medical Institute, Bethesda, MD, USA. mwaldor@research.bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Jan; Vol. 613 (7945), pp. 721-728. Date of Electronic Publication: 2022 Nov 30.
DOI: 10.1038/s41586-022-05569-1
Abstrakt: The microbial cell wall is essential for maintenance of cell shape and resistance to external stressors 1 . The primary structural component of the cell wall is peptidoglycan, a glycopolymer with peptide crosslinks located outside of the cell membrane 1 . Peptidoglycan biosynthesis and structure are responsive to shifting environmental conditions such as pH and salinity 2-6 , but the mechanisms underlying such adaptations are incompletely understood. Precursors of peptidoglycan and other cell surface glycopolymers are synthesized in the cytoplasm and then delivered across the cell membrane bound to the recyclable lipid carrier undecaprenyl phosphate 7 (C55-P, also known as UndP). Here we identify the DUF368-containing and DedA transmembrane protein families as candidate C55-P translocases, filling a critical gap in knowledge of the proteins required for the biogenesis of microbial cell surface polymers. Gram-negative and Gram-positive bacteria lacking their cognate DUF368-containing protein exhibited alkaline-dependent cell wall and viability defects, along with increased cell surface C55-P levels. pH-dependent synthetic genetic interactions between DUF368-containing proteins and DedA family members suggest that C55-P transporter usage is dynamic and modulated by environmental inputs. C55-P transporter activity was required by the cholera pathogen for growth and cell shape maintenance in the intestine. We propose that conditional transporter reliance provides resilience in lipid carrier recycling, bolstering microbial fitness both inside and outside the host.
(© 2022. The Author(s).)
Databáze: MEDLINE
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