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Undecaprenyl phosphate translocases confer conditional microbial fitness
Division of Infectious Diseases, Brigham and Women’s Hospital, MA, Boston, United States; Department of Microbiology, Harvard Medical School, MA, Boston, United States; Department of Biology, Massachusetts Institute of Technology, MA, Cambridge, United States.
Division of Infectious Diseases, Brigham and Women’s Hospital, MA, Boston, United States; Department of Microbiology, Harvard Medical School, MA, Boston, United States; Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Division of Infectious Diseases, Brigham and Women’s Hospital, MA, Boston, United States; Department of Microbiology, Harvard Medical School, MA, Boston, United States.
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2023 (Engelska)Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 613, nr 7945, s. 721-728Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The microbial cell wall is essential for maintenance of cell shape and resistance to external stressors1. The primary structural component of the cell wall is peptidoglycan, a glycopolymer with peptide crosslinks located outside of the cell membrane1. Peptidoglycan biosynthesis and structure are responsive to shifting environmental conditions such as pH and salinity2–6, 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 phosphate7 (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.

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Springer Nature, 2023. Vol. 613, nr 7945, s. 721-728
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
URN: urn:nbn:se:umu:diva-213596DOI: 10.1038/s41586-022-05569-1ISI: 000912326300001PubMedID: 36450355Scopus ID: 2-s2.0-85145983873OAI: oai:DiVA.org:umu-213596DiVA, id: diva2:1792163
Forskningsfinansiär
NIH (National Institutes of Health)Tillgänglig från: 2023-08-28 Skapad: 2023-08-28 Senast uppdaterad: 2023-08-28Bibliografiskt granskad

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Bueno, EmilioCava, Felipe

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Molekylär Infektionsmedicin, Sverige (MIMS)Umeå Centre for Microbial Research (UCMR)Institutionen för molekylärbiologi (Medicinska fakulteten)
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Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

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