YhdP, TamB, and YdbH Are Redundant but Essential for Growth and Lipid Homeostasis of the Gram-Negative Outer Membrane

Ruiz, Natividad; Davis, Rebecca; Kumar, Sujeet

doi:10.1128/mbio.02714-21

Cited by 49 publications

(108 citation statements)

References 86 publications

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“…Lastly, YhdP has been implicated in GPL transport as loss of YhdP slows IM rupture in a high flux GPL transport background [ 6 ]. Furthermore, a recent publication also reveals the essentiality and redundancy of YhdP, TamB, and YdbH [ 37 ]. The authors also demonstrate a disruption in OM lipid homeostasis in yhdP tamB mutants, but do not establish defects in GPL transport [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a recent publication also reveals the essentiality and redundancy of YhdP, TamB, and YdbH [ 37 ]. The authors also demonstrate a disruption in OM lipid homeostasis in yhdP tamB mutants, but do not establish defects in GPL transport [ 37 ]. Given the work presented here and the impressive work of our colleagues [ 6 , 37 ], it is clear that this remarkable family of proteins plays an important role in cell envelope biogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…The authors also demonstrate a disruption in OM lipid homeostasis in yhdP tamB mutants, but do not establish defects in GPL transport [ 37 ]. Given the work presented here and the impressive work of our colleagues [ 6 , 37 ], it is clear that this remarkable family of proteins plays an important role in cell envelope biogenesis. Our data reveals the accumulation of GPLs in the IM and excess LPS shuttled to the OM in the absence of these proteins, providing a model where the AsmA clan is responsible for the highly sought-after anterograde GPL transport system.…”

Section: Discussionmentioning

confidence: 99%

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Absence of YhdP, TamB, and YdbH leads to defects in glycerophospholipid transport and cell morphology in Gram-negative bacteria

2022

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The outer membrane (OM) of Gram-negative bacteria provides the cell with a formidable barrier that excludes external threats. The two major constituents of this asymmetric barrier are lipopolysaccharide (LPS) found in the outer leaflet, and glycerophospholipids (GPLs) in the inner leaflet. Maintaining the asymmetric nature and balance of LPS to GPLs in the OM is critical for bacterial viability. The biosynthetic pathways of LPS and GPLs are well characterized, but unlike LPS transport, how GPLs are translocated to the OM remains enigmatic. Understanding this aspect of cell envelope biology could provide a foundation for new antibacterial therapies. Here, we report that YhdP and its homologues, TamB and YdbH, members of the “AsmA-like” family, are critical for OM integrity and necessary for proper GPL transport to the OM. The absence of the two largest AsmA-like proteins (YhdP and TamB) leads to cell lysis and antibiotic sensitivity, phenotypes that are rescued by reducing LPS synthesis. We also find that yhdP, tamB double mutants shed excess LPS through outer membrane vesicles, presumably to maintain OM homeostasis when normal anterograde GPL transport is disrupted. Moreover, a yhdP, tamB, ydbH triple mutant is synthetically lethal, but if GPL transport is partially restored by overexpression of YhdP, the cell shape adjusts to accommodate increased membrane content as the cell accumulates GPLs in the IM. Our results therefore suggest a model in which “AsmA-like” proteins transport GPLs to the OM, and when hindered, changes in cell shape and shedding of excess LPS aids in maintaining OM asymmetry.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Absence of YhdP, TamB, and YdbH leads to defects in glycerophospholipid transport and cell morphology in Gram-negative bacteria

2022

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“…This would exactly resemble the Lpt β-jellyroll bridges that provide the route for LPS molecules to be exported to the OM [5], perhaps shedding additional insights into the true nature of the enigmatic Bayer bridges. In the case of TamB, the presence of its cognate OM partner TamA is necessary for its newly-discovered function in OM lipid homeostasis [69]; in this regard, YhdP, YdbH, and other AsmA-like homologs may also require additional OM factors. E.…”

Section: Asma-like Superfamily Proteinsmentioning

confidence: 99%

“…All these observations point towards putative function(s) in membrane biology. Very recently, YhdP, TamB, and YdbH are found to be collectively essential for growth and OM homeostasis in E. coli [69,70], making them prime candidates for the critical process of PL transport. Steady-state lipid analyses revealed that cells lacking both YhdP and TamB produce more OM vesicles, and these vesicles have reduced PL:LPS ratios [70].…”

Section: Asma-like Superfamily Proteinsmentioning

confidence: 99%

Of zones, bridges and chaperones – phospholipid transport in bacterial outer membrane assembly and homeostasis

Yeow

Chng

2022

Microbiology

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The outer membrane (OM) is a formidable permeability barrier that protects Gram-negative bacteria from detergents and antibiotics. It possesses exquisite lipid asymmetry, requiring the placement and retention of lipopolysaccharides (LPS) in the outer leaflet, and phospholipids (PLs) in the inner leaflet. To establish OM lipid asymmetry, LPS are transported from the inner membrane (IM) directly to the outer leaflet of the OM. In contrast, mechanisms for PL trafficking across the cell envelope are much less understood. In this review, we summarize and discuss recent advances in our understanding of PL transport, making parallel comparisons to well-established pathways for OM lipoprotein (Lol) and LPS (Lpt). Insights into putative PL transport systems highlight possible connections back to the ‘Bayer bridges’, adhesion zones between the IM and the OM that had been observed more than 50 years ago, and proposed as passages for export of OM components, including LPS and PLs.

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Envelope-Stress Sensing Mechanism of Rcs and Cpx Signaling Pathways in Gram-Negative Bacteria

2023

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YhdP, TamB, and YdbH Are Redundant but Essential for Growth and Lipid Homeostasis of the Gram-Negative Outer Membrane

Cited by 49 publications

References 86 publications

Absence of YhdP, TamB, and YdbH leads to defects in glycerophospholipid transport and cell morphology in Gram-negative bacteria

Absence of YhdP, TamB, and YdbH leads to defects in glycerophospholipid transport and cell morphology in Gram-negative bacteria

Of zones, bridges and chaperones – phospholipid transport in bacterial outer membrane assembly and homeostasis

Envelope-Stress Sensing Mechanism of Rcs and Cpx Signaling Pathways in Gram-Negative Bacteria

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