The LpxL acyltransferase is required for normal growth and penta-acylation of lipid A in Burkholderia cenocepacia

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      The LpxL acyltransferase is required for normal growth and penta-acylation of lipid A in Burkholderia cenocepacia. / Mohamed, Yasmine Fathy; Hamad, Mohamad; Ortega, Ximena p.; Valvano, Miguel a.

      In: Molecular Microbiology, Vol. 104, No. 1, 04.2017, p. 144-162.

      Research output: Research - peer-reviewArticle

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      Mohamed, Yasmine Fathy ; Hamad, Mohamad ; Ortega, Ximena p. ; Valvano, Miguel a./ The LpxL acyltransferase is required for normal growth and penta-acylation of lipid A in Burkholderia cenocepacia. In: Molecular Microbiology. 2017 ; Vol. 104, No. 1. pp. 144-162

      Bibtex

      @article{163a6327ecd241e89aba2af2a43e8d5f,
      title = "The LpxL acyltransferase is required for normal growth and penta-acylation of lipid A in Burkholderia cenocepacia",
      abstract = "Lipid A anchors the lipopolysaccharide (LPS) to the outer membrane and is usually composed of a hexa-acylated diglucosamine backbone. Burkholderia cenocepacia, an opportunistic pathogen, produces a mixture of tetra- and penta-acylated lipid A. {"}Late{"} acyltransferases add secondary acyl chains to lipid A after the incorporation of four primary acyl chains to the diglucosamine backbone. Here, we report that B. cenocepacia has only one late acyltransferase, LpxL (BCAL0508), which adds a myristoyl chain to the 2' position of lipid A resulting in penta-acylated lipid A. We also identified PagL (BCAL0788), which acts as an outer membrane lipase by removing the primary β-hydroxymyristate (3-OH-C14:0) chain at the 3 position, leading to tetra-acylated lipid A. Unlike PagL, LpxL depletion caused reduced cell growth and defects in cell morphology, both of which were suppressed by overexpressing the LPS flippase MsbA (BCAL2408), suggesting that lipid A molecules lacking the fifth acyl chain contributed by LpxL are not good substrates for the flippase. We also show that intracellular B. cenocepacia within macrophages produced more penta-acylated lipid A, suggesting lipid A penta-acylation in B. cenocepacia is required not only for bacterial growth and morphology but also for adaptation to intracellular lifestyle.",
      author = "Mohamed, {Yasmine Fathy} and Mohamad Hamad and Ortega, {Ximena p.} and Valvano, {Miguel a.}",
      year = "2017",
      month = "4",
      doi = "10.1111/mmi.13618",
      volume = "104",
      pages = "144--162",
      journal = "Molecular Microbiology",
      issn = "0950-382X",
      publisher = "Wiley-Blackwell",
      number = "1",

      }

      RIS

      TY - JOUR

      T1 - The LpxL acyltransferase is required for normal growth and penta-acylation of lipid A in Burkholderia cenocepacia

      AU - Mohamed,Yasmine Fathy

      AU - Hamad,Mohamad

      AU - Ortega,Ximena p.

      AU - Valvano,Miguel a.

      PY - 2017/4

      Y1 - 2017/4

      N2 - Lipid A anchors the lipopolysaccharide (LPS) to the outer membrane and is usually composed of a hexa-acylated diglucosamine backbone. Burkholderia cenocepacia, an opportunistic pathogen, produces a mixture of tetra- and penta-acylated lipid A. "Late" acyltransferases add secondary acyl chains to lipid A after the incorporation of four primary acyl chains to the diglucosamine backbone. Here, we report that B. cenocepacia has only one late acyltransferase, LpxL (BCAL0508), which adds a myristoyl chain to the 2' position of lipid A resulting in penta-acylated lipid A. We also identified PagL (BCAL0788), which acts as an outer membrane lipase by removing the primary β-hydroxymyristate (3-OH-C14:0) chain at the 3 position, leading to tetra-acylated lipid A. Unlike PagL, LpxL depletion caused reduced cell growth and defects in cell morphology, both of which were suppressed by overexpressing the LPS flippase MsbA (BCAL2408), suggesting that lipid A molecules lacking the fifth acyl chain contributed by LpxL are not good substrates for the flippase. We also show that intracellular B. cenocepacia within macrophages produced more penta-acylated lipid A, suggesting lipid A penta-acylation in B. cenocepacia is required not only for bacterial growth and morphology but also for adaptation to intracellular lifestyle.

      AB - Lipid A anchors the lipopolysaccharide (LPS) to the outer membrane and is usually composed of a hexa-acylated diglucosamine backbone. Burkholderia cenocepacia, an opportunistic pathogen, produces a mixture of tetra- and penta-acylated lipid A. "Late" acyltransferases add secondary acyl chains to lipid A after the incorporation of four primary acyl chains to the diglucosamine backbone. Here, we report that B. cenocepacia has only one late acyltransferase, LpxL (BCAL0508), which adds a myristoyl chain to the 2' position of lipid A resulting in penta-acylated lipid A. We also identified PagL (BCAL0788), which acts as an outer membrane lipase by removing the primary β-hydroxymyristate (3-OH-C14:0) chain at the 3 position, leading to tetra-acylated lipid A. Unlike PagL, LpxL depletion caused reduced cell growth and defects in cell morphology, both of which were suppressed by overexpressing the LPS flippase MsbA (BCAL2408), suggesting that lipid A molecules lacking the fifth acyl chain contributed by LpxL are not good substrates for the flippase. We also show that intracellular B. cenocepacia within macrophages produced more penta-acylated lipid A, suggesting lipid A penta-acylation in B. cenocepacia is required not only for bacterial growth and morphology but also for adaptation to intracellular lifestyle.

      U2 - 10.1111/mmi.13618

      DO - 10.1111/mmi.13618

      M3 - Article

      VL - 104

      SP - 144

      EP - 162

      JO - Molecular Microbiology

      T2 - Molecular Microbiology

      JF - Molecular Microbiology

      SN - 0950-382X

      IS - 1

      ER -

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