PediatricHelicobacter pyloriIsolates Display Distinct Gene Coding Capacities and Virulence Gene Marker Profiles

Abstract

Helicobacter pylori strains display remarkable genetic diversity, and the presence of strains bearing the toxigenic vacA s1 allele, a complete cag pathogenicity island (PAI), cagA alleles containing multiple EPIYA phosphorylation sites, and expressing the BabA adhesin correlates with development of gastroduodenal disease in adults. To better understand the genetic variability present among pediatric strains and its relationship to disease, we characterized H. pylori strains infecting 47 pediatric North American patients. Prevalence of mixed infection was assessed by random amplified polymorphic DNA analysis of multiple H. pylori clones from each patient. Microarray-based comparative genomic hybridization was used to examine the genomic content of the pediatric strains. The cagA and vacA alleles were further characterized by allele-specific PCR. A range of EPIYA motif configurations were observed for the cagA gene, which was present in strains from 22 patients (47%), but only 19 (41%) patients contained a complete cag PAI. Thirty patients (64%) were infected with a strain having the vacA s1 allele, and 28 patients (60%) had the babA gene. The presence of a functional cag PAI was correlated with ulcer disease (P ‫؍‬ 0.0095). In spite of declining rates of H. pylori infection in North America, at least 11% of patients had mixed infection. Pediatric strains differ in their spectrum of strainvariable genes and percentage of absent genes in comparison to adult strains. Most children were infected with H. pylori strains lacking the cag PAI, but the presence of a complete cag PAI, in contrast to other virulence markers, was associated with more severe gastroduodenal disease.

Clinical Relevance and Diversity of Two Homologous Genes Encoding Glycosyltransferases in Helicobacter pylori

“…It is important to emphasize that the clinical strains used in the present study were isolated from children, thus leading to a more reliable model of the early natural conditions of the infection and one that is less influenced by environmental determinants. Several studies report that pediatric H. pylori strains display more distinct virulence profiles than those isolated from adults (13,18,25,34). Accordingly, the severity of H. pylori-associated disease in younger subjects may be closely related to the virulence of the strain, independently of the host factors, which may not be the case among adults.…”

Benefits of Helicobacter pylori cagE genotyping in addition to cagA genotyping: a Bulgarian study

“…Likewise, fewer (41%) North American children were found to possess cagPAI ? strains compared with adults (62%) (Talarico et al 2009). Conversely, the prevalence of duodenal ulcer promoting (dupA) genepositive strains in Brazil was higher in strains from children than in those from adults (Gomes et al 2008).…”

Prevalence of Infection With Caga-Positive Helicobacter Pylori Strains Among Children and Adolescents in Southern Brazil

“…Previous studies with adults from southern Brazil, including from southern Brazil, including from Porto Alegre, found prevalence rates of cagA-positive infection ranging from 65% to 71% (24,26) , as well as an association between presence of this gene and duodenal ulcer (26) and gastric cancer (19) . The difference between adults and children from the same population may denote a different behavior of the infection in children (18,20,31) .…”

“…Although infection rates are decreasing in pediatric populations from different regions, with prevalence ranging from less than 10% to 28% (16,17,18,21,27) , H. pylori still plays an important role in the pathogenesis of peptic ulcer disease, gastric adenocarcinoma and gastric mucosaassociated lymphoid tissue lymphoma (2) -diseases that carry high morbidity and mortality rates. H. pylori infection is acquired predominantly in childhood (18,31) . Once the gastric mucosa is colonized, the bacterium is likely to remain there for decades, if not throughout the life of the host (34) .…”

“…Helicobacter pylori (H. pylori) is one of the commonest pathogens in humans, affecting more than 50% of the world's population (31) . Although infection rates are decreasing in pediatric populations from different regions, with prevalence ranging from less than 10% to 28% (16,17,18,21,27) , H. pylori still plays an important role in the pathogenesis of peptic ulcer disease, gastric adenocarcinoma and gastric mucosaassociated lymphoid tissue lymphoma (2) -diseases that carry high morbidity and mortality rates.…”