Acid‐induced expression of an LPS‐associated gene in <i>Helicobacter pylori</i>

McGowan, Catherine C.; Necheva, Antoaneta; Thompson, Stuart A.; Cover, Timothy L.; Blaser, Martin J.

doi:10.1046/j.1365-2958.1998.t01-1-01079.x

Cited by 90 publications

(72 citation statements)

References 59 publications

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“…5), which strengthens the notion that a minimum LOS structure is required for acid resistance and/or adaptation. In H. pylori, acid shock caused the up-regulation of a lipopolysaccharide gene (wbcJ) encoding a product that is required for O antigen synthesis and Lewis X and/or Y expression (54). In the absence of external urea, a wbcJ mutant was more sensitive to acid killing (54), supporting the idea that lipopolysaccharide is protective against acid.…”

Section: Discussionmentioning

confidence: 99%

Identification of Campylobacter jejuni Genes Contributing to Acid Adaptation by Transcriptional Profiling and Genome-Wide Mutagenesis

Reid

Pandey

Palyada

et al. 2008

Appl Environ Microbiol

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In order to cause disease, the food-and waterborne pathogen Campylobacter jejuni must face the extreme acidity of the host stomach as well as cope with pH fluctuations in the intestine. In the present study, C. jejuni NCTC 11168 was grown under mildly acidic conditions mimicking those encountered in the intestine. The resulting transcriptional profiles revealed how this bacterium fine-tunes gene expression in response to acid stress. This adaptation involves the differential expression of respiratory pathways, the induction of genes for phosphate transport, and the repression of energy generation and intermediary metabolism genes. We also generated and screened a transposon-based mutant library to identify genes required for wild-type levels of growth under mildly acidic conditions. This screen highlighted the important role played by cell surface components (flagella, the outer membrane, capsular polysaccharides, and lipooligosaccharides) in the acid stress response of C. jejuni. Our data also revealed that a limited correlation exists between genes required for growth under acidic conditions and genes differentially expressed in response to acid. To gain a comprehensive picture of the acid stress response of C. jejuni, we merged transcriptional profiles obtained from acid-adapted cells and cells subjected to acid shock. Genes encoding the transcriptional regulator PerR and putative oxidoreductase subunits Cj0414 and Cj0415 were among the few up-regulated under both acid stress conditions. As a Cj0415 mutant was acid sensitive, it is likely that these genes are crucial to the acid stress response of C. jejuni and consequently are important for host colonization.

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Section: Discussionmentioning

confidence: 99%

Identification of Campylobacter jejuni Genes Contributing to Acid Adaptation by Transcriptional Profiling and Genome-Wide Mutagenesis

Reid

Pandey

Palyada

et al. 2008

Appl Environ Microbiol

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“…Previously, genes encoding the heat shock protein Hsp70 and cell wall composition, as well as cagA (23,25,31), have been observed to be up-regulated in acid, and random mutagenesis showed that at least 10 genes were essential for growth at pH 4.8 (6). Gamma-glutamyl transpeptidase has been shown to be essential for colonization (13).…”

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confidence: 99%

Acid-Adaptive Genes of Helicobacter pylori

Wen

Marcus

Matrubutham³

et al. 2003

Infect Immun

193

278

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Helicobacter pylori is the only neutralophile that has been able to colonize the human stomach by using a variety of acid-adaptive mechanisms. One of the adaptive mechanisms is increased buffering due to expression of an acid-activated inner membrane urea channel, UreI, and a neutral pH-optimum intrabacterial urease. To delineate other possible adaptive mechanisms, changes in gene expression in response to acid exposure were examined using genomic microarrays of H. pylori exposed to different levels of external pH (7.4, 6.2, 5.5, and 4.5) for 30 min in the absence and presence of 5 mM urea. Gene expression was correlated with intrabacterial pH measured using 2,7-bis-(2-carboxyethyl)-5-carboxyfluorescein and compared to that observed with exposure to 42°C for 30 min. Microarrays containing the 1,534 open reading frames of H. pylori strain 26695 were hybridized with cDNAs from control (pH 7.4; labeled with Cy3) and acidic (labeled with Cy5) conditions. The intrabacterial pH was 8.1 at pH 7.4, fell to 5.3 at pH 4.5, and rose to 6.2 with urea. About 200 genes were up-regulated and ϳ100 genes were down-regulated at pH 4.5 in the absence of urea, and about half that number changed in the presence of urea. These genes included pH-homeostatic, transcriptional regulatory, motility, cell envelope, and pathogenicity genes. The up-regulation of some pH-homeostatic genes was confirmed by real-time PCR. There was little overlap with the genes induced by temperature stress. These results suggest that H. pylori has evolved multifaceted acid-adaptive mechanisms enabling it to colonize the stomach that may be novel targets for eliminating infection.

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“…Interestingly, neither the 4-keto intermediate nor its reduced derivative are present in the LPS of H. pylori (4,5,46). In addition, all genes involved in the biosynthesis of the precursors necessary for LPS assembly have been identified (30,36,44) and are distinct from flaA1 and wbpB. Consequently, although it is expected that flaA1 and wbpB might affect LPS synthesis based on sequence homologies, such an effect is not anticipated to occur directly via production of LPS sugar precursors.…”

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TheHelicobacter pylori flaA1andwbpBGenes Control Lipopolysaccharide and Flagellum Synthesis and Function

et al. 2004

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flaA1 and wbpB are conserved genes with unknown biological function in Helicobacter pylori. Since both genes are predicted to be involved in lipopolysaccharide (LPS) biosynthesis, flagellum assembly, or protein glycosylation, they could play an important role in the pathogenesis of H. pylori. To determine their biological role, both genes were disrupted in strain NCTC 11637. Both mutants exhibited altered LPS, with loss of most O-antigen and core modification, and increased sensitivity to sodium dodecyl sulfate compared to wild-type bacteria. These defects could be complemented in a gene-specific manner. Also, flaA1 could complement these defects in the wbpB mutant, suggesting a potential redundancy of the reductase activity encoded by both genes. Both mutants were nonmotile, although the wbpB mutant still produced flagella. The defect in the flagellum functionality of this mutant was not due to a defect in flagellin glycosylation since flagellins from wild-type strain NCTC 11637 were shown not to be glycosylated. The flaA1 mutant produced flagellins but no flagellum. Overall, the similar phenotypes observed for both mutants and the complementation of the wbpB mutant by flaA1 suggest that both genes belong to the same biosynthesis pathway. The data also suggest that flaA1 and wbpB are at the interface between several pathways that govern the expression of different virulence factors. We propose that FlaA1 and WbpB synthesize sugar derivatives dedicated to the glycosylation of proteins which are involved in LPS and flagellum production and that glycosylation regulates the activity of these proteins.Helicobacter pylori is a spiral-shaped gram-negative microaerophilic bacterium that was first isolated from the human stomach in 1984 (42). It is estimated that 70% of the worldwide population is infected by this bacterium. Most infections are asymptomatic, but they can also lead to gastric ulcers and cancers (26,51,66,69). The relationship between colonization by H. pylori and the onset of the disease is not fully understood. Hence, it is important to identify essential bacterial virulence factors and elucidate their contribution to disease development.Several virulence factors contribute to the stringent host and tissue specificities exhibited by H. pylori (37). Among them, urease helps neutralize the acidic pH surrounding the bacteria and allows their survival in the gastric environment (21, 45). In addition, the spiral shape and unipolar flagella of H. pylori confer on the bacterium a corkscrew motion that enhances motility in the viscous gastric mucus (32, 33, 63) and is essential for host colonization (22,23,35). Lipopolysaccharide (LPS) is also important for the virulence of H. pylori since strains lacking the O antigen are significantly impaired in their capacity to colonize the murine stomach (40). The H. pylori O antigen is composed of N-acetyl-D-glucosamine, L-fucose, and D-galactose (4, 5, 46), which form structural motifs that are identical to human blood group antigens Lewis X, Y, and b (4,5,[46][47][48]....

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Acid‐induced expression of an LPS‐associated gene in Helicobacter pylori

Cited by 90 publications

References 59 publications

Identification of Campylobacter jejuni Genes Contributing to Acid Adaptation by Transcriptional Profiling and Genome-Wide Mutagenesis

Identification of Campylobacter jejuni Genes Contributing to Acid Adaptation by Transcriptional Profiling and Genome-Wide Mutagenesis

Acid-Adaptive Genes of Helicobacter pylori

TheHelicobacter pylori flaA1andwbpBGenes Control Lipopolysaccharide and Flagellum Synthesis and Function

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