A Helicobacter pylori homolog of eukaryotic flotillin is involved in cholesterol accumulation, epithelial cell responses and host colonization

Melanie L. Hutton, Kimberley D'Costa, Amanda E. Rossiter, Lin Wang, Lorinda Turner, David L. Steer, Seth L. Masters, Ben A. Croker, Maria Kaparakis-Liaskos, Richard L. Ferrero

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as "lipid rafts." Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H. pylori protein (HP0248) with homology to the flotillin proteins normally found in the cholesterol-enriched domains of eukaryotic cells. As shown for eukaryotic flotillin proteins, HP0248 was detected in detergent-resistant membrane fractions of H. pylori. Importantly, H. pylori HP0248 mutants contained lower levels of cholesterol than wild-type bacteria (P < 0.01). HP0248 mutant bacteria also exhibited defects in type IV secretion functions, as indicated by reduced IL-8 responses and CagA translocation in epithelial cells (P < 0.05), and were less able to establish a chronic infection in mice than wild-type bacteria (P < 0.05). Thus, we have identified an H. pylori flotillin protein and shown its importance for bacterial virulence. Taken together, the data demonstrate important roles for H. pylori flotillin in host-pathogen interactions. We propose that H. pylori flotillin may be required for the organization of virulence proteins into membrane raft-like structures in this pathogen.

Original languageEnglish
Article number219
Number of pages13
JournalFrontiers in Cellular and Infection Microbiology
Volume7
DOIs
Publication statusPublished - 6 Jun 2017

Keywords

  • Bacterial flotillins
  • CagA
  • Cholesterol
  • Helicobacter pylori
  • Lipid rafts
  • Membrane raft domains
  • Type IV secretion system

Cite this

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title = "A Helicobacter pylori homolog of eukaryotic flotillin is involved in cholesterol accumulation, epithelial cell responses and host colonization",
abstract = "The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as {"}lipid rafts.{"} Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H. pylori protein (HP0248) with homology to the flotillin proteins normally found in the cholesterol-enriched domains of eukaryotic cells. As shown for eukaryotic flotillin proteins, HP0248 was detected in detergent-resistant membrane fractions of H. pylori. Importantly, H. pylori HP0248 mutants contained lower levels of cholesterol than wild-type bacteria (P < 0.01). HP0248 mutant bacteria also exhibited defects in type IV secretion functions, as indicated by reduced IL-8 responses and CagA translocation in epithelial cells (P < 0.05), and were less able to establish a chronic infection in mice than wild-type bacteria (P < 0.05). Thus, we have identified an H. pylori flotillin protein and shown its importance for bacterial virulence. Taken together, the data demonstrate important roles for H. pylori flotillin in host-pathogen interactions. We propose that H. pylori flotillin may be required for the organization of virulence proteins into membrane raft-like structures in this pathogen.",
keywords = "Bacterial flotillins, CagA, Cholesterol, Helicobacter pylori, Lipid rafts, Membrane raft domains, Type IV secretion system",
author = "Hutton, {Melanie L.} and Kimberley D'Costa and Rossiter, {Amanda E.} and Lin Wang and Lorinda Turner and Steer, {David L.} and Masters, {Seth L.} and Croker, {Ben A.} and Maria Kaparakis-Liaskos and Ferrero, {Richard L.}",
year = "2017",
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A Helicobacter pylori homolog of eukaryotic flotillin is involved in cholesterol accumulation, epithelial cell responses and host colonization. / Hutton, Melanie L.; D'Costa, Kimberley; Rossiter, Amanda E.; Wang, Lin; Turner, Lorinda; Steer, David L.; Masters, Seth L.; Croker, Ben A.; Kaparakis-Liaskos, Maria; Ferrero, Richard L.

In: Frontiers in Cellular and Infection Microbiology, Vol. 7, 219, 06.06.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A Helicobacter pylori homolog of eukaryotic flotillin is involved in cholesterol accumulation, epithelial cell responses and host colonization

AU - Hutton, Melanie L.

AU - D'Costa, Kimberley

AU - Rossiter, Amanda E.

AU - Wang, Lin

AU - Turner, Lorinda

AU - Steer, David L.

AU - Masters, Seth L.

AU - Croker, Ben A.

AU - Kaparakis-Liaskos, Maria

AU - Ferrero, Richard L.

PY - 2017/6/6

Y1 - 2017/6/6

N2 - The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as "lipid rafts." Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H. pylori protein (HP0248) with homology to the flotillin proteins normally found in the cholesterol-enriched domains of eukaryotic cells. As shown for eukaryotic flotillin proteins, HP0248 was detected in detergent-resistant membrane fractions of H. pylori. Importantly, H. pylori HP0248 mutants contained lower levels of cholesterol than wild-type bacteria (P < 0.01). HP0248 mutant bacteria also exhibited defects in type IV secretion functions, as indicated by reduced IL-8 responses and CagA translocation in epithelial cells (P < 0.05), and were less able to establish a chronic infection in mice than wild-type bacteria (P < 0.05). Thus, we have identified an H. pylori flotillin protein and shown its importance for bacterial virulence. Taken together, the data demonstrate important roles for H. pylori flotillin in host-pathogen interactions. We propose that H. pylori flotillin may be required for the organization of virulence proteins into membrane raft-like structures in this pathogen.

AB - The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as "lipid rafts." Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H. pylori protein (HP0248) with homology to the flotillin proteins normally found in the cholesterol-enriched domains of eukaryotic cells. As shown for eukaryotic flotillin proteins, HP0248 was detected in detergent-resistant membrane fractions of H. pylori. Importantly, H. pylori HP0248 mutants contained lower levels of cholesterol than wild-type bacteria (P < 0.01). HP0248 mutant bacteria also exhibited defects in type IV secretion functions, as indicated by reduced IL-8 responses and CagA translocation in epithelial cells (P < 0.05), and were less able to establish a chronic infection in mice than wild-type bacteria (P < 0.05). Thus, we have identified an H. pylori flotillin protein and shown its importance for bacterial virulence. Taken together, the data demonstrate important roles for H. pylori flotillin in host-pathogen interactions. We propose that H. pylori flotillin may be required for the organization of virulence proteins into membrane raft-like structures in this pathogen.

KW - Bacterial flotillins

KW - CagA

KW - Cholesterol

KW - Helicobacter pylori

KW - Lipid rafts

KW - Membrane raft domains

KW - Type IV secretion system

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U2 - 10.3389/fcimb.2017.00219

DO - 10.3389/fcimb.2017.00219

M3 - Article

VL - 7

JO - Frontiers in Cellular and Infection Microbiology

JF - Frontiers in Cellular and Infection Microbiology

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ER -