Stress‐induced host membrane remodeling protects from infection by non‐motile bacterial pathogens

Tawk, Caroline; Nigro, Giulia; Lopes, Ines Rodrigues; Aguilar, Carmen; Lisowski, Clivia; Mano, Miguel; Sansonetti, Philippe J.; Vogel, Jörg; Eulálio, Ana

doi:10.15252/embj.201798529

Cited by 17 publications

(11 citation statements)

References 77 publications

(104 reference statements)

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“…Recently, bacterial flagellar motility was described to help bacteria to reach preferred sites in host plasma membrane containing sphingolipid-rich domains (56). Our findings show that not only motility but also bacterial flagella per se, acting as an adhesin on lipids, help bacteria to reach their host cell targets.…”

Section: Discussionsupporting

confidence: 50%

The impact of plasma membrane lipid composition on flagella-mediated adhesion of enterohemorrhagicEscherichia coli

Cazzola

Lemaire

Acket

et al. 2020

Preprint

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AbstractEnterohemorrhagic Escherichia coli (EHEC) O157:H7 is a major cause of foodborne gastrointestinal illness. The adhesion of EHEC on host tissues is the first step enabling bacterial colonization. Adhesins like fimbriae and flagella mediate this mechanism. Here, we studied the interaction of the bacterial flagellum with the host cell’s plasma membrane using Giant Unilamellar Vesicles (GUVs) as a biologically relevant model. Cultured cell lines contain many different molecular components including proteins and glycoproteins. In contrast, with GUVs we can characterize the bacterial mode of interaction solely with a defined lipid part of the cell membrane. Bacterial adhesion on GUVs was dependent on the presence of the flagellar filament and its motility. By testing different phospholipid head groups, the nature of the fatty acid chains or the liposome curvature, we found that lipid packing is a key parameter to enable bacterial adhesion. Using HT-29 cells grown in the presence of polyunsaturated fatty acid (α-linolenic acid) or saturated fatty acid (palmitic acid), we found that α-linolenic acid reduced adhesion of wild type EHEC but not of a non-flagellated mutant. Finally, our results reveal that the presence of flagella is advantageous for the bacteria to bind to lipid rafts. We speculate that polyunsaturated fatty acids prevent flagellar adhesion on membrane bilayers and play a clear role for optimal host colonization. Flagella-mediated adhesion to plasma membranes has broad implications to host-pathogen interactions.ImportanceBacterial adhesion is a crucial step to allow bacteria to colonize their hosts, invade tissues and form biofilm. Enterohemorrhagic E. coli O157:H7 is a human pathogen and the causative agent of diarrhea and hemorrhagic colitis. Here, we use biomimetic membrane models and cell lines to decipher the impact of lipid content of the plasma membrane on enterohemorrhagic E. coli flagella-mediated adhesion. Our findings provide evidence that polyunsaturated fatty acid (α-linolenic acid) inhibits E. coli flagella adhesion to the plasma membrane in a mechanism separate from its antimicrobial and anti-inflammatory functions. In addition, we confirm that cholesterol-enriched lipid microdomains, often called lipid rafts are important in bacterial adhesion. These findings significantly strengthen plasma membrane adhesion via bacterial flagella in an important human pathogen. This mechanism represents a promising target for the development of novel anti-adhesion therapies.

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Section: Discussionsupporting

confidence: 50%

The impact of plasma membrane lipid composition on flagella-mediated adhesion of enterohemorrhagicEscherichia coli

Cazzola

Lemaire

Acket

et al. 2020

Preprint

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“…Moreover, ASM is involved in most effective host membrane remodeling during enteropathogenic infection with Shigella spp. resulting in decreased binding of pathogens to epithelial cells and therefore, impeding abovementioned or other pathogens from reinfection, which was proposed as a novel stress-responsive cell-autonomous defense mechanism ( 76 ).…”

Section: Asm Is Our Buddymentioning

confidence: 99%

Keep Your Friends Close, but Your Enemies Closer: Role of Acid Sphingomyelinase During Infection and Host Response

Chung

Claus

2021

Front. Med.

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Breakdown of the inert and constitutive membrane building block sphingomyelin to the highly active lipid mediator ceramide by extracellularly active acid sphingomyelinase is tightly regulated during stress response and opens the gate for invading pathogens, triggering the immune response, development of remote organ failure, and tissue repair following severe infection. How do one enzyme and one mediator manage all of these affairs? Under physiological conditions, the enzyme is located in the lysosomes and takes part in the noiseless metabolism of sphingolipids, but following stress the protein is secreted into circulation. When secreted, acid sphingomyelinase (ASM) is able to hydrolyze sphingomyelin present at the outer leaflet of membranes to ceramide. Its generation troubles the biophysical context of cellular membranes resulting in functional assembly and reorganization of proteins and receptors, also embedded in highly conserved response mechanisms. As a consequence of cellular signaling, not only induction of cell death but also proliferation, differentiation, and fibrogenesis are affected. Here, we discuss the current state of the art on both the impact and function of the enzyme during host response and damage control. Also, the potential role of lysosomotropic agents as functional inhibitors of this upstream alarming cascade is highlighted.

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“…The eukaryotic plasma membrane plays an important role in the interaction of flagellated bacteria with host cells during the early stages of infection 6 . The flagella of Salmonella Typhimurium, Escherichia coli and Pseudomonas aeruginosa can function as adhesion molecules [7][8][9] mediating the contact to various lipidic plasma membrane components, including cholesterol, phospholipids, sulfolipids and the gangliosides GM1 and aGM1 [10][11][12][13] .…”

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confidence: 99%

Methylation of Salmonella Typhimurium flagella promotes bacterial adhesion and host cell invasion

et al. 2020

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The long external filament of bacterial flagella is composed of several thousand copies of a single protein, flagellin. Here, we explore the role played by lysine methylation of flagellin in Salmonella, which requires the methylase FliB. We show that both flagellins of Salmonella enterica serovar Typhimurium, FliC and FljB, are methylated at surface-exposed lysine residues by FliB. A Salmonella Typhimurium mutant deficient in flagellin methylation is outcompeted for gut colonization in a gastroenteritis mouse model, and methylation of flagellin promotes bacterial invasion of epithelial cells in vitro. Lysine methylation increases the surface hydrophobicity of flagellin, and enhances flagella-dependent adhesion of Salmonella to phosphatidylcholine vesicles and epithelial cells. Therefore, posttranslational methylation of flagellin facilitates adhesion of Salmonella Typhimurium to hydrophobic host cell surfaces, and contributes to efficient gut colonization and host infection.

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Stress‐induced host membrane remodeling protects from infection by non‐motile bacterial pathogens

Cited by 17 publications

References 77 publications

The impact of plasma membrane lipid composition on flagella-mediated adhesion of enterohemorrhagicEscherichia coli

The impact of plasma membrane lipid composition on flagella-mediated adhesion of enterohemorrhagicEscherichia coli

Keep Your Friends Close, but Your Enemies Closer: Role of Acid Sphingomyelinase During Infection and Host Response

Methylation of Salmonella Typhimurium flagella promotes bacterial adhesion and host cell invasion

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