Vitamin B 6 is required for full motility and virulence in Helicobacter pylori

Alexandra Grubman, Alexandra Phillips, Marie Thibonnier, Maria Kaparakis-Liaskos, Chad Johnson, Jean -Michael Thiberge, Fiona J Radcliffe, Chantal Ecobichon, Agnes Labigne, Hilde de Reuse, George L Mendz, Richard L Ferrero

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Despite recent advances in our understanding of how Helicobacter pylori causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in H. pylori, we generated low-infectivity variants of a mouse-colonizing H. pylori strain using the classical technique of in vitro attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the Escherichia coli vitamin B(6) biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with E. coli confirmed H. pylori PdxA and PdxJ to be bona fide homologs of vitamin B(6) biosynthesis enzymes. Importantly, H. pylori PdxA was required for optimal growth in vitro and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B(6) is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in H. pylori. Thus, for the first time, we identify vitamin B(6) biosynthesis enzymes as novel virulence factors in bacteria. Interestingly, pdxA and pdxJ orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.
Original languageEnglish
Article numbere00112-10
Number of pages9
JournalmBio
Volume1
Issue number3
DOIs
Publication statusPublished - 2010

Cite this

Grubman, Alexandra ; Phillips, Alexandra ; Thibonnier, Marie ; Kaparakis-Liaskos, Maria ; Johnson, Chad ; Thiberge, Jean -Michael ; Radcliffe, Fiona J ; Ecobichon, Chantal ; Labigne, Agnes ; de Reuse, Hilde ; Mendz, George L ; Ferrero, Richard L. / Vitamin B 6 is required for full motility and virulence in Helicobacter pylori. In: mBio. 2010 ; Vol. 1, No. 3.
@article{98932912e0294adb826082851da70444,
title = "Vitamin B 6 is required for full motility and virulence in Helicobacter pylori",
abstract = "Despite recent advances in our understanding of how Helicobacter pylori causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in H. pylori, we generated low-infectivity variants of a mouse-colonizing H. pylori strain using the classical technique of in vitro attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the Escherichia coli vitamin B(6) biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with E. coli confirmed H. pylori PdxA and PdxJ to be bona fide homologs of vitamin B(6) biosynthesis enzymes. Importantly, H. pylori PdxA was required for optimal growth in vitro and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B(6) is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in H. pylori. Thus, for the first time, we identify vitamin B(6) biosynthesis enzymes as novel virulence factors in bacteria. Interestingly, pdxA and pdxJ orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.",
author = "Alexandra Grubman and Alexandra Phillips and Marie Thibonnier and Maria Kaparakis-Liaskos and Chad Johnson and Thiberge, {Jean -Michael} and Radcliffe, {Fiona J} and Chantal Ecobichon and Agnes Labigne and {de Reuse}, Hilde and Mendz, {George L} and Ferrero, {Richard L}",
year = "2010",
doi = "10.1128/mBio.00112-10",
language = "English",
volume = "1",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "3",

}

Grubman, A, Phillips, A, Thibonnier, M, Kaparakis-Liaskos, M, Johnson, C, Thiberge, J-M, Radcliffe, FJ, Ecobichon, C, Labigne, A, de Reuse, H, Mendz, GL & Ferrero, RL 2010, 'Vitamin B 6 is required for full motility and virulence in Helicobacter pylori' mBio, vol. 1, no. 3, e00112-10. https://doi.org/10.1128/mBio.00112-10

Vitamin B 6 is required for full motility and virulence in Helicobacter pylori. / Grubman, Alexandra; Phillips, Alexandra; Thibonnier, Marie; Kaparakis-Liaskos, Maria; Johnson, Chad; Thiberge, Jean -Michael; Radcliffe, Fiona J; Ecobichon, Chantal; Labigne, Agnes; de Reuse, Hilde; Mendz, George L; Ferrero, Richard L.

In: mBio, Vol. 1, No. 3, e00112-10, 2010.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Vitamin B 6 is required for full motility and virulence in Helicobacter pylori

AU - Grubman, Alexandra

AU - Phillips, Alexandra

AU - Thibonnier, Marie

AU - Kaparakis-Liaskos, Maria

AU - Johnson, Chad

AU - Thiberge, Jean -Michael

AU - Radcliffe, Fiona J

AU - Ecobichon, Chantal

AU - Labigne, Agnes

AU - de Reuse, Hilde

AU - Mendz, George L

AU - Ferrero, Richard L

PY - 2010

Y1 - 2010

N2 - Despite recent advances in our understanding of how Helicobacter pylori causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in H. pylori, we generated low-infectivity variants of a mouse-colonizing H. pylori strain using the classical technique of in vitro attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the Escherichia coli vitamin B(6) biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with E. coli confirmed H. pylori PdxA and PdxJ to be bona fide homologs of vitamin B(6) biosynthesis enzymes. Importantly, H. pylori PdxA was required for optimal growth in vitro and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B(6) is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in H. pylori. Thus, for the first time, we identify vitamin B(6) biosynthesis enzymes as novel virulence factors in bacteria. Interestingly, pdxA and pdxJ orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.

AB - Despite recent advances in our understanding of how Helicobacter pylori causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in H. pylori, we generated low-infectivity variants of a mouse-colonizing H. pylori strain using the classical technique of in vitro attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the Escherichia coli vitamin B(6) biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with E. coli confirmed H. pylori PdxA and PdxJ to be bona fide homologs of vitamin B(6) biosynthesis enzymes. Importantly, H. pylori PdxA was required for optimal growth in vitro and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B(6) is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in H. pylori. Thus, for the first time, we identify vitamin B(6) biosynthesis enzymes as novel virulence factors in bacteria. Interestingly, pdxA and pdxJ orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000542/pdf/mBio00112-10.pdf

U2 - 10.1128/mBio.00112-10

DO - 10.1128/mBio.00112-10

M3 - Article

VL - 1

JO - mBio

JF - mBio

SN - 2161-2129

IS - 3

M1 - e00112-10

ER -