Lipoprotein Transport: Greasing the Machines of Outer Membrane Biogenesis

Grabowicz, Marcin

doi:10.1002/bies.201700187

Cited by 32 publications

(30 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Why lipoprotein N-acylation is advantageous in bacterial membranes is an outstanding question. The widespread occurrence of N-terminal modification, though, does suggest a more universal selective pressure in nature beyond Gram-negative-specific transport (14,47). The genetic coregulation between lit2 and copper tolerance determinants in Firmicutes reported here, in tandem with the peculiar distribution of N-terminal modification machinery, may provide a clue.…”

Section: Discussionmentioning

confidence: 75%

Copper-Induced Expression of a Transmissible Lipoprotein Intramolecular Transacylase Alters Lipoprotein Acylation and the Toll-Like Receptor 2 Response to Listeria monocytogenes

2019

View full text Add to dashboard Cite

Bacterial lipoproteins are globular proteins anchored to the extracytoplasmic surfaces of cell membranes through lipidation at a conserved N-terminal cysteine. Lipoproteins contribute to an array of important cellular functions for bacteria, as well as being a focal point for innate immune system recognition through binding to Toll-like receptor 2 (TLR2) heterodimer complexes. Although lipoproteins are conserved among nearly all classes of bacteria, the presence and type of α-amino-linked acyl chain are highly variable and even strain specific within a given bacterial species. The reason for lyso-lipoprotein formation and N-acylation variability in general is presently not fully understood. In Enterococcus faecalis, lipoproteins are anchored by an N-acyl-S-monoacyl-glyceryl cysteine (lyso form) moiety installed by a chromosomally encoded lipoprotein intramolecular transacylase (Lit). Here, we describe a mobile genetic element common to environmental isolates of Listeria monocytogenes and Enterococcus spp. encoding a functional Lit ortholog (Lit2) that is cotranscribed with several well-established copper resistance determinants. Expression of Lit2 is tightly regulated, and induction by copper converts lipoproteins from the diacylglycerol-modified form characteristic of L. monocytogenes type strains to the α-amino-modified lyso form observed in E. faecalis. Conversion to the lyso form through either copper addition to media or constitutive expression of lit2 decreases TLR2 recognition when using an activated NF-κB secreted embryonic alkaline phosphatase reporter assay. While lyso formation significantly diminishes TLR2 recognition, lyso-modified lipoprotein is still predominantly recognized by the TLR2/TLR6 heterodimer. IMPORTANCE The induction of lipoprotein N-terminal remodeling in response to environmental copper in Gram-positive bacteria suggests a more general role in bacterial cell envelope physiology. N-terminal modification by lyso formation, in particular, simultaneously modulates the TLR2 response in direct comparison to their diacylglycerol-modified precursors. Thus, use of copper as a frontline antimicrobial control agent and ensuing selection raises the potential of diminished innate immune sensing and enhanced bacterial virulence.

show abstract

Section: Discussionmentioning

confidence: 75%

Copper-Induced Expression of a Transmissible Lipoprotein Intramolecular Transacylase Alters Lipoprotein Acylation and the Toll-Like Receptor 2 Response to Listeria monocytogenes

2019

View full text Add to dashboard Cite

show abstract

“…The first step in lipoprotein maturation after translocation into the periplasm involves the transfer of a diacyl moiety from PG ( 121 ), and its absence presumably stalls maturation at this point. However, the OM lipoproteins LptE and BamD are essential in E. coli , so the viability of these lpp mutant strains suggests that alternate maturation pathways or sources of diacylglycerol must exist ( 122 , 123 ). As BamA and LptD are essential OMPs, the fact that bacteria can still grow and divide in these strains (albeit poorly) suggests that other lipids can moonlight for the loss of PE, PG, or CL or that there is no absolute need for a particular phospholipid type as a minimum requirement for OMP biogenesis in E. coli .…”

Section: Another Brick In the Wall: Building The Ommentioning

confidence: 99%

Role of the lipid bilayer in outer membrane protein folding in Gram-negative bacteria

Horne

Brockwell

Radford

2020

Journal of Biological Chemistry

101

View full text Add to dashboard Cite

β-barrel outer membrane proteins (OMPs) represent the major proteinaceous component of the outer membrane (OM) of Gram-negative bacteria. These proteins perform key roles in cell structure and morphology, nutrient acquisition, colonisation and invasion, and protection against external toxic threats such as antibiotics. To become functional, OMPs must fold and insert into a crowded and asymmetric OM that lacks much freely accessible lipid. This feat is accomplished in the absence of an external energy source and is thought to be driven by the high thermodynamic stability of folded OMPs in the OM. With such a stable fold, the challenge that bacteria face in assembling OMPs into the OM is how to overcome the initial energy barrier of membrane insertion. In this review, we highlight the roles of the lipid environment and the OM in modulating the OMP folding landscape and discuss the factors that guide folding in vitro and in vivo. We particularly focus on the composition, architecture and physical properties of the OM and how an understanding of the folding properties of OMPs in vitro can help explain the challenges they encounter during folding in vivo. Current models of OMP biogenesis in the cellular environment are still in flux, but the stakes for improving the accuracy of these models are high. Since OMP folding is an essential process in all Gram-negative bacteria, and considering the looming crisis of widespread microbial drug resistance, to bring down the powerful, OMP-supported barrier against antibiotics, we must first understand how bacterial cells build it.

show abstract

“…These results indicate the importance of the IM localization for the full activity of MepM. Similarly, we constructed three chimeric proteins as follows: MepS-Flag with the Flag-tag at the C-terminus, DsbA(ss)-MepS-Flag with the signal sequence of DsbA at the N-terminus instead of its own signal sequence and the palmitoylation residue to target it to the periplasm, and MepS(S28D&R29D)-Flag whose OM-targeted signal (Ser 2+ -Arg 3+ ) is substituted to the IM retention signal (Asp 2+ -Asp 3+ ) (Grabowicz, 2018). Like MepM, mislocalized MepS proteins also have the partial activity, but they could not sufficiently restore the growth of the mepS mutant under EDTA stress at low arabinose concentrations ( Figure 3B).…”

Section: The Importance Of the Localization Of Mepm And Meps For Theimentioning

confidence: 99%

Genetic Evidence for Distinct Functions of Peptidoglycan Endopeptidases in Escherichia coli

et al. 2020

View full text Add to dashboard Cite

Peptidoglycan (PG) is an essential component of the bacterial exoskeleton that plays a pivotal role in the maintenance of cell shape and resistance to cell lysis under high turgor pressures. The synthesis and degradation of PG must be tightly regulated during bacterial cell elongation and division. Unlike enzymes involved in PG synthesis, PG hydrolases show high redundancy in many bacteria including Escherichia coli. In this study, we showed that PG endopeptidases have distinct roles in cell growth and division. Phenotypic analysis of mutants lacking one of seven PG endopeptidases identified a MepM-specific phenotype, salt sensitivity, and a MepS-specific phenotype, EDTA sensitivity. Complementation test in each phenotype showed that the phenotype of the mepM mutant was restored only by MepM, whereas the phenotype of the mepS mutant was restored by MepS or by overexpression of MepH, PbpG, or MepM. These distinct phenotypes depend on both the specific localizations and specific domains of MepM and MepS. Finally, using the identified phenotypes, we revealed that MepM and MepH were genetically associated with both penicillin-binding protein 1a (PBP1a) and PBP1b, whereas MepS and PbpG were genetically associated with only PBP1b. Notably, a defect in PBP1a or PBP1b phenocopied the mepM mutant, suggesting the importance of MepM on PG synthesis. Therefore, our results indicate that each PG endopeptidase plays a distinct role in cell growth and division, depending on its distinct domains and cellular localizations.

show abstract

Lipoprotein Transport: Greasing the Machines of Outer Membrane Biogenesis

Cited by 32 publications

References 111 publications

Copper-Induced Expression of a Transmissible Lipoprotein Intramolecular Transacylase Alters Lipoprotein Acylation and the Toll-Like Receptor 2 Response to Listeria monocytogenes

Copper-Induced Expression of a Transmissible Lipoprotein Intramolecular Transacylase Alters Lipoprotein Acylation and the Toll-Like Receptor 2 Response to Listeria monocytogenes

Role of the lipid bilayer in outer membrane protein folding in Gram-negative bacteria

Genetic Evidence for Distinct Functions of Peptidoglycan Endopeptidases in Escherichia coli

Contact Info

Product

Resources

About