Salmonella Tol-Pal Reduces Outer Membrane Glycerophospholipid Levels for Envelope Homeostasis and Survival during Bacteremia

Masilamani, Revathi; Cian, Melina B.; Dalebroux, Zachary D.

doi:10.1128/iai.00173-18

Cited by 42 publications

(56 citation statements)

References 66 publications

(112 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TolB is a soluble periplasmic protein in the Tol-Pal complex, the conserved complex of cell envelopes in Gram-negative bacteria (Lazzaroni et al, 2002). The mutant genotypes of the Tol-Pal proteins vary in length and exhibit some chain reaction compared with the WT in Salmonella typhimurium (Masilamani et al, 2018). In K. pneumoniae, the lengths of each tolB or rcsF overexpression strains were longer than those of the crp strain, indicating that the alteration of cell length in crp was through regulating multiple genes, not just one gene, to adapt to the environment.…”

Section: Discussionmentioning

confidence: 99%

Cyclic AMP-CRP Modulates the Cell Morphology of Klebsiella pneumoniae in High-Glucose Environment

Liu

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

Bacteria can modify their morphology in response to environmental stimuli for survival or host defense evasion. The rich glucose in vivo or in the Luria-Bertani (LB) medium shortened the cell length of Klebsiella pneumoniae. The environmental glucose decreased the levels of cyclic AMP (cAMP) and the transcription of crp, which declined the cAMP-cAMP receptor protein (cAMP-CRP) activity. The cell length of crp deletion mutant was significantly shorter than that of the wild type (0.981 ± 0.057 µm vs. 2.415 ± 0.075 µm, P < 0.001). These results indicated that the high environmental glucose alters the bacterial morphology to a round form through regulating the activity of cAMP-CRP complex. Comparative proteomics analysis showed increased expression of 10 proteins involved in cell division or cell wall biosynthesis in the crp deletion strain. Five of them (ompA, tolB, ybgC, ftsI, and rcsF) were selected to verify their expression in the high-glucose environment, and overexpression of tolB or rcsF shortened the bacterial length similar to that of the crp deletion strain. Electrophoretic mobility shift assay indicated that CRP directly negatively regulates the transcription of tolB and rcsF by binding to the promoter regions. This study first proved the role and partial regulation mechanism of CRP in altering cell morphology during infection and provided a theoretical basis for elucidating the mechanism in diabetes mellitus susceptible to K. pneumoniae.

show abstract

Section: Discussionmentioning

confidence: 99%

Cyclic AMP-CRP Modulates the Cell Morphology of Klebsiella pneumoniae in High-Glucose Environment

Liu

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Using steadystate radioactive labeling of cellular lipids, it was demonstrated that cells lacking the Tol-Pal complex maintain WT levels of LPS but accumulate excess PLs in the OM. This molecular defect, which is also observed in S. Typhimurium (79), likely destabilizes the OM and can potentially account for the OM phenotypes described above. It was further established that PL buildup in the OM in tol-pal mutants is due to defects in retrograde PL transport.…”

Section: The Tol-pal Complexmentioning

confidence: 75%

Lipid trafficking across the Gram-negative cell envelope

Shrivastava

Chng

2019

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Karen G. Fleming The outer membrane (OM) of Gram-negative bacteria exhibits unique lipid asymmetry, with lipopolysaccharides (LPS) residing in the outer leaflet and phospholipids (PLs) in the inner leaflet. This asymmetric bilayer protects the bacterium against intrusion of many toxic substances, including antibiotics and detergents, yet allows acquisition of nutrients necessary for growth. To build the OM and ensure its proper function, the cell produces OM constituents in the cytoplasm or inner membrane and transports these components across the aqueous periplasmic space separating the two membranes. Of note, the processes by which the most basic membrane building blocks, i.e. PLs, are shuttled across the cell envelope remain elusive. This review highlights our current understanding (or lack thereof) of bacterial PL trafficking, with a focus on recent developments in the field. We adopt a mechanistic approach and draw parallels and comparisons with well-characterized systems, particularly OM lipoprotein and LPS transport, to illustrate key challenges in intermembrane lipid trafficking. Pathways that transport PLs across the bacterial cell envelope are fundamental to OM biogenesis and homeostasis and are potential molecular targets that could be exploited for antibiotic development.

show abstract

“…In this study, we have identified suppressor mutations that can rescue OM permeability defects in cells lacking the Tol-Pal complex, which are known to contain excess PLs in their OM (Shrivastava et al, 2017;Masilamani et al, 2018). Mutations in ECA biosynthesis restore OM barrier function, thus blocking entry of large antibiotics and reducing periplasmic leakiness, in tolpal mutant strains (Figs.…”

Section: Discussionmentioning

confidence: 99%

Mutations in enterobacterial common antigen biosynthesis restore outer membrane barrier function inEscherichia coli tol-palmutants

Jiang

Tan

Shrivastava

et al. 2018

Preprint

View full text Add to dashboard Cite

23The outer membrane (OM) is an essential component of the Gram-negative bacterial cell 24 envelope that protects cells against external threats such as antibiotics. To maintain a stable and 25 functional OM barrier, cells require distinct mechanisms to ensure a balance of proteins and 26 lipids in the membrane. Crucial to this is the proper transport and assembly of various OM 27 components, of which the process of phospholipid (PL) transport is least understood. How OM 28 assembly pathways are coordinated to achieve homeostasis is also unclear. In this study, we set 29 out to identify potential mechanism(s) that can alleviate OM lipid dyshomeostasis in Escherichia 30 coli. Cells lacking the Tol-Pal complex accumulate excess PLs in the OM due to defective 31 retrograde PL transport. Here, we isolated mutations in enterobacterial common antigen (ECA) 32 biosynthesis that restore OM barrier function in these strains; build-up of biosynthetic 33 intermediates along the ECA pathway is key to this rescue. Interestingly, these ECA mutations 34 re-establish OM lipid homeostasis in cells lacking the Tol-Pal complex yet do not act by 35 restoring retrograde PL transport. Furthermore, a novel diacylglycerol pyrophosphoryl-linked 36 ECA species structurally similar to PLs can be detected in the inner membrane of ECA mutants. 37 We therefore propose a model where these unique species may modulate anterograde PL 38 transport to overcome OM lipid dyshomeostasis. Our work provides insights into bacterial lipid 39 transport across the cell envelope and highlights previously unappreciated effects of ECA 40 intermediates in OM biology. 41 42 3 Author Summary 43 44Biological membranes define cellular boundaries, allow compartmentalization, and represent a 45 prerequisite for life; yet, our understanding of membrane biogenesis and stability remain 46 rudimentary. In Gram-negative bacteria, the outer membrane prevents entry of toxic substances, 47 conferring intrinsic resistance against many antibiotics. How the outer membrane is assembled, 48 specifically lipid trafficking processes are not well understood. How this membrane is stably 49 maintained is also unclear. In this study, we discovered that intermediates along the biosynthetic 50 pathway of an exopolysaccharide exhibit stabilizing effects on outer membranes with lipid 51 imbalance in Escherichia coli. Our work suggests that these intermediates modulate phospholipid 52 trafficking within the double-membrane cell envelope to achieve outer membrane lipid 53 homeostasis. Furthermore, it provides a starting point to begin identifying hitherto unknown 54 phospholipid transport systems in Gram-negative bacteria, which are potential targets for the 55 development of future antibiotics. 56 57 58 Gram-negative bacteria are surrounded by a multilayered cell envelope consisting of the 59 inner membrane (IM), the peptidoglycan layer, and the outer membrane (OM). This envelope 60 structure, in particular the OM, plays an essential role in preventing toxic molecules from 61 en...

show abstract

Salmonella Tol-Pal Reduces Outer Membrane Glycerophospholipid Levels for Envelope Homeostasis and Survival during Bacteremia

Cited by 42 publications

References 66 publications

Cyclic AMP-CRP Modulates the Cell Morphology of Klebsiella pneumoniae in High-Glucose Environment

Cyclic AMP-CRP Modulates the Cell Morphology of Klebsiella pneumoniae in High-Glucose Environment

Lipid trafficking across the Gram-negative cell envelope

Mutations in enterobacterial common antigen biosynthesis restore outer membrane barrier function inEscherichia coli tol-palmutants

Contact Info

Product

Resources

About