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Ulcerogenic Helicobacter pylori strains isolated from children: a contribution to get insight into the virulence of the bacteria.

Vitoriano I, Saraiva-Pava KD, Rocha-Gonçalves A, Santos A, Lopes AI, Oleastro M, Roxo-Rosa M - PLoS ONE (2011)

Bottom Line: Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins.To uncover virulence features, we compared the proteome of these two groups of H. pylori strains.In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors.

View Article: PubMed Central - PubMed

Affiliation: Faculdade de Engenharia, Universidade Católica Portuguesa, Rio de Mouro, Portugal.

ABSTRACT
Infection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD). In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA "on" status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility-associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors.

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Schematic diagram of the DU development in children upon H. pylori infection.The virulence of the pediatric PUD-associated H. pylori strains results from a synergy between their natural ability to better adapt to the hostile human stomach and their virulence factors. Adaptation is ensured by: higher motility (↑ FlaA, ↑ FlgE, ↓ HELP_0944, ↑ HPAG1_1081, and ↑ HPG27_1480), higher ability to survive under low pH conditions (↑ UreA and B and ↑ putative aldo-keto reductase), better antioxidant defenses against inflammation (↑ Pfr, ↑ NapA and ↓ KatA), modified metabolism (↓ HyuA, ↓ AspA, ↑ Pgk, ↓ ScoA and B, ↑AroQ, ↓ Porγ, ↑ FldA, ↓ RpsA and ↓ CysS), adhesion (indicated by a anchor) mediated by “on” OipA and HomB. Virulence factors (indicated by a bomb): cagA and VacAs1. 1 – Infection; 2 – Host response (acid hypersecretion and inflammation); 3 – duodenal acid injury (Duodenal Ulcer, indicated by an explosion symbol). Dotted arrow - Time line.
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pone-0026265-g005: Schematic diagram of the DU development in children upon H. pylori infection.The virulence of the pediatric PUD-associated H. pylori strains results from a synergy between their natural ability to better adapt to the hostile human stomach and their virulence factors. Adaptation is ensured by: higher motility (↑ FlaA, ↑ FlgE, ↓ HELP_0944, ↑ HPAG1_1081, and ↑ HPG27_1480), higher ability to survive under low pH conditions (↑ UreA and B and ↑ putative aldo-keto reductase), better antioxidant defenses against inflammation (↑ Pfr, ↑ NapA and ↓ KatA), modified metabolism (↓ HyuA, ↓ AspA, ↑ Pgk, ↓ ScoA and B, ↑AroQ, ↓ Porγ, ↑ FldA, ↓ RpsA and ↓ CysS), adhesion (indicated by a anchor) mediated by “on” OipA and HomB. Virulence factors (indicated by a bomb): cagA and VacAs1. 1 – Infection; 2 – Host response (acid hypersecretion and inflammation); 3 – duodenal acid injury (Duodenal Ulcer, indicated by an explosion symbol). Dotted arrow - Time line.

Mentions: Taking advantage of our pediatric strains, we decided to evaluate the proteome of each of the 10 Portuguese H. pylori strains. Their proteome profiles were consistent (Figure 3) and comparable with proteome profiles in databases [14]. Moreover, 27 proteins were found to be differentially expressed between PUD and NUD strains (Table 2). It should be stressed that these differences in protein expression profile are intrinsic to the bacteria and were not induced by the environment. In fact, despite having experienced completely different environmental conditions in vivo, in this study they were grown under the same controlled conditions which did not fully resemble their natural niche. An important observation was noted for the group of PUD-associated strains: the strain 499/02 presented unique features which required special attention given that it was isolated from a child with GU and the other four were associated with DU. Although these diseases share important molecular mechanisms in their pathogenesis, they are characterized by different patterns of colonization, gastritis and gastric acid secretion [2]. Our results suggest that the ability to induce one of these situations is reflected in the proteome of the implicated H. pylori strains and should be investigated further. Thus, the strain 499/02 was considered separately in the subsequent analysis. Figure 5 resumes the following discussion of the differentially expressed proteins grouped according to their known function. We were not able to identify spot 7 but its role should be important role as it was absent from the proteome of all PUD strains.


Ulcerogenic Helicobacter pylori strains isolated from children: a contribution to get insight into the virulence of the bacteria.

Vitoriano I, Saraiva-Pava KD, Rocha-Gonçalves A, Santos A, Lopes AI, Oleastro M, Roxo-Rosa M - PLoS ONE (2011)

Schematic diagram of the DU development in children upon H. pylori infection.The virulence of the pediatric PUD-associated H. pylori strains results from a synergy between their natural ability to better adapt to the hostile human stomach and their virulence factors. Adaptation is ensured by: higher motility (↑ FlaA, ↑ FlgE, ↓ HELP_0944, ↑ HPAG1_1081, and ↑ HPG27_1480), higher ability to survive under low pH conditions (↑ UreA and B and ↑ putative aldo-keto reductase), better antioxidant defenses against inflammation (↑ Pfr, ↑ NapA and ↓ KatA), modified metabolism (↓ HyuA, ↓ AspA, ↑ Pgk, ↓ ScoA and B, ↑AroQ, ↓ Porγ, ↑ FldA, ↓ RpsA and ↓ CysS), adhesion (indicated by a anchor) mediated by “on” OipA and HomB. Virulence factors (indicated by a bomb): cagA and VacAs1. 1 – Infection; 2 – Host response (acid hypersecretion and inflammation); 3 – duodenal acid injury (Duodenal Ulcer, indicated by an explosion symbol). Dotted arrow - Time line.
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Related In: Results  -  Collection

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pone-0026265-g005: Schematic diagram of the DU development in children upon H. pylori infection.The virulence of the pediatric PUD-associated H. pylori strains results from a synergy between their natural ability to better adapt to the hostile human stomach and their virulence factors. Adaptation is ensured by: higher motility (↑ FlaA, ↑ FlgE, ↓ HELP_0944, ↑ HPAG1_1081, and ↑ HPG27_1480), higher ability to survive under low pH conditions (↑ UreA and B and ↑ putative aldo-keto reductase), better antioxidant defenses against inflammation (↑ Pfr, ↑ NapA and ↓ KatA), modified metabolism (↓ HyuA, ↓ AspA, ↑ Pgk, ↓ ScoA and B, ↑AroQ, ↓ Porγ, ↑ FldA, ↓ RpsA and ↓ CysS), adhesion (indicated by a anchor) mediated by “on” OipA and HomB. Virulence factors (indicated by a bomb): cagA and VacAs1. 1 – Infection; 2 – Host response (acid hypersecretion and inflammation); 3 – duodenal acid injury (Duodenal Ulcer, indicated by an explosion symbol). Dotted arrow - Time line.
Mentions: Taking advantage of our pediatric strains, we decided to evaluate the proteome of each of the 10 Portuguese H. pylori strains. Their proteome profiles were consistent (Figure 3) and comparable with proteome profiles in databases [14]. Moreover, 27 proteins were found to be differentially expressed between PUD and NUD strains (Table 2). It should be stressed that these differences in protein expression profile are intrinsic to the bacteria and were not induced by the environment. In fact, despite having experienced completely different environmental conditions in vivo, in this study they were grown under the same controlled conditions which did not fully resemble their natural niche. An important observation was noted for the group of PUD-associated strains: the strain 499/02 presented unique features which required special attention given that it was isolated from a child with GU and the other four were associated with DU. Although these diseases share important molecular mechanisms in their pathogenesis, they are characterized by different patterns of colonization, gastritis and gastric acid secretion [2]. Our results suggest that the ability to induce one of these situations is reflected in the proteome of the implicated H. pylori strains and should be investigated further. Thus, the strain 499/02 was considered separately in the subsequent analysis. Figure 5 resumes the following discussion of the differentially expressed proteins grouped according to their known function. We were not able to identify spot 7 but its role should be important role as it was absent from the proteome of all PUD strains.

Bottom Line: Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins.To uncover virulence features, we compared the proteome of these two groups of H. pylori strains.In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors.

View Article: PubMed Central - PubMed

Affiliation: Faculdade de Engenharia, Universidade Católica Portuguesa, Rio de Mouro, Portugal.

ABSTRACT
Infection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD). In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA "on" status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility-associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors.

Show MeSH
Related in: MedlinePlus