The Unique Phospholipidome of the Enteric Pathogen Campylobacter jejuni: Lysophosholipids Are Required for Motility at Low Oxygen Availability

Cao, Xuefeng; Brouwers, Jos F.; Dijk, Linda van; Lest, Chris H.A. van de; Parker, Craig T.; Huynh, Steven; Putten, Jos P. M. van; Kelly, David J.; Wösten, Marc M. S. M.

doi:10.1016/j.jmb.2020.07.012

Cited by 17 publications

(23 citation statements)

References 46 publications

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“…Of note, lysoPE14 and lysoPE16 make up 50% of the C. jejuni lysoPE molecules. 12 Together, these results indicate that short lysoPE species disrupt the integrity of the cell membrane of horse erythrocytes.…”

Section: Resultsmentioning

confidence: 77%

“…We previously showed that the bacterial pathogen Campylobacter jejuni possesses a wide spectrum of LPLs that varies dependent on the environmental conditions. 12 C. jejuni is the leading cause of bacterial foodborne human gastroenteritis in developed countries. 13 Symptomatic infection typically involves intestinal inflammation, fever, and bloody diarrhea.…”

Section: Introductionmentioning

confidence: 99%

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Campylobacter jejuni permeabilizes the host cell membrane by short chain lysophosphatidylethanolamines

et al. 2022

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Lysophospholipids (LPLs) are crucial for regulating epithelial integrity and homeostasis in eukaryotes, however the effects of LPLs produced by bacteria on host cells is largely unknown. The membrane of the human bacterial pathogen Campylobacter jejuni is rich in LPLs. Although C. jejuni possesses several virulence factors, it lacks traditional virulence factors like type III secretion systems, present in most enteropathogens. Here, we provide evidence that membrane lipids lysophosphatidylethanolamines (lysoPEs) of C. jejuni are able to lyse erythrocytes and are toxic for HeLa and Caco-2 cells. Lactate dehydrogenase (LDH) release assays and confocal microscopy revealed that lysoPE permeabilizes the cells. LysoPE toxicity was partially rescued by oxidative stress inhibitors, indicating that intracellular reactive oxygen species may contribute to the cell damage. Our results show that especially the short-chain lysoPEs (C:14) which is abundantly present in the C. jejuni membrane may be considered as a novel virulence factor.

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Section: Resultsmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Campylobacter jejuni permeabilizes the host cell membrane by short chain lysophosphatidylethanolamines

et al. 2022

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“…The LplT/Aas system is commonly present in Gram‐negative bacteria though missing from A. tumefaciens and S. meliloti (Harvat et al ., 2005; Lin et al ., 2016). LplT homologues are also absent in C. jejuni , which is thought to be the reason for the exceptionally high levels of L‐PLs in this bacterium (Cao et al ., 2020). The E. coli Mla ABC transporter system has been shown to shuttle PE, PG and, to some extent, CL across the periplasmic lumen via the soluble periplasmic protein MlaC (Malinverni and Silhavy, 2009; Ekiert et al ., 2017).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the commonly occurring glycerophospholipids (GPLs) phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL), or various phosphorus‐free lipids, such as glycolipids or ornithine lipids (OL), they account for less than 1% of total lipids in most Gram‐positive and Gram‐negative bacteria under normal conditions (Hubac et al ., 1992; Sohlenkamp and Geiger, 2016; López‐Lara and Geiger, 2017). In some proteobacteria, however, L‐PLs are major membrane constituents, and in Campylobacter jejuni they are needed for normal motility at low oxygen conditions (Sohlenkamp and Geiger, 2016; Cao et al ., 2020). L‐PLs in bacterial membranes originate from various endogenous and exogenous sources; as metabolic intermediates in membrane adaptation, lipid homeostasis or lipoprotein maturation, or upon contact with secretory phospholipase A 2 (sPLA 2 ) (Homma et al ., 1981; Jackowski and Rock, 1986; Henriksen et al ., 2010).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the unusual lipid bis(monoacylglycero)phosphate in environmental bacteria

Czolkoss

Borgert

Poppenga

et al. 2021

Environmental Microbiology

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Summary The bacterial membrane is constantly remodelled in response to environmental conditions and the external supply of precursor molecules. Some bacteria are able to acquire exogenous lyso‐phospholipids and convert them to the corresponding phospholipids. Here, we report that some soil‐dwelling bacteria have alternative options to metabolize lyso‐phosphatidylglycerol (L‐PG). We find that the plant‐pathogen Agrobacterium tumefaciens takes up this mono‐acylated phospholipid and converts it to two distinct isoforms of the non‐canonical lipid bis(monoacylglycero)phosphate (BMP). Chromatographic separation and quadrupole‐time‐of‐flight MS/MS analysis revealed the presence of two possible BMP stereo configurations acylated at either of the free hydroxyl groups of the glycerol head group. BMP accumulated in the inner membrane and did not visibly alter cell morphology and growth behaviour. The plant‐associated bacterium Sinorhizobium meliloti was also able to convert externally provided L‐PG to BMP. Other bacteria like Pseudomonas fluorescens and Escherichia coli metabolized L‐PG after cell disruption, suggesting that BMP production in the natural habitat relies both on dedicated uptake systems and on head‐group acylation enzymes. Overall, our study adds two previously overlooked phospholipids to the repertoire of bacterial membrane lipids and provides evidence for the remarkable condition‐responsive adaptation of bacterial membranes.

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“…Only recently, it was recognized that the membrane composition of many bacteria is much more diverse than originally anticipated (Sohlenkamp and Geiger 2016 ). The human pathogen Campylobacter jejuni for example accumulates unusually large amounts of the lysophospholipids lyso-PE (LPE) and lyso-PG (LPG) (Cao et al 2020 ). Other bacteria, like Flavobacterium ummariense or Bdellovibrio bacteriovorus , accumulate significant amounts of PS, which is usually directly converted to PE (Lata et al 2012 ; Nguyen et al 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Recombinant and endogenous ways to produce methylated phospholipids in Escherichia coli

Kleetz

Vasilopoulos

Czolkoss

et al. 2021

Appl Microbiol Biotechnol

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Escherichia coli is the daily workhorse in molecular biology research labs and an important platform microorganism in white biotechnology. Its cytoplasmic membrane is primarily composed of the phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL). As in most other bacteria, the typical eukaryotic phosphatidylcholine (PC) is not a regular component of the E. coli membrane. PC is known to act as a substrate in various metabolic or catabolic reactions, to affect protein folding and membrane insertion, and to activate proteins that originate from eukaryotic environments. Options to manipulate the E. coli membrane to include non-native lipids such as PC might make it an even more powerful and versatile tool for biotechnology and protein biochemistry. This article outlines different strategies how E. coli can be engineered to produce PC and other methylated PE derivatives. Several of these approaches rely on the ectopic expression of genes from natural PC-producing organisms. These include PC synthases, lysolipid acyltransferases, and several phospholipid N-methyltransferases with diverse substrate and product preferences. In addition, we show that E. coli has the capacity to produce PC by its own enzyme repertoire provided that appropriate precursors are supplied. Screening of the E. coli Keio knockout collection revealed the lysophospholipid transporter LplT to be responsible for the uptake of lyso-PC, which is then further acylated to PC by the acyltransferase-acyl carrier protein synthetase Aas. Overall, our study shows that the membrane composition of the most routinely used model bacterium can readily be tailored on demand.Key points• Escherichia coli can be engineered to produce non-native methylated PE derivatives.• These lipids can be produced by foreign and endogenous proteins.• Modification of E. coli membrane offers potential for biotechnology and research. Graphical abstract

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The Unique Phospholipidome of the Enteric Pathogen Campylobacter jejuni: Lysophosholipids Are Required for Motility at Low Oxygen Availability

Cited by 17 publications

References 46 publications

Campylobacter jejuni permeabilizes the host cell membrane by short chain lysophosphatidylethanolamines

Campylobacter jejuni permeabilizes the host cell membrane by short chain lysophosphatidylethanolamines

Synthesis of the unusual lipid bis(monoacylglycero)phosphate in environmental bacteria

Recombinant and endogenous ways to produce methylated phospholipids in Escherichia coli

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