BackgroundThe human gastric pathogen Helicobacter pylori is co-evolved with its host and therefore, origins and expansion of multiple populations and sub populations of H. pylori mirror ancient human migrations. Ancestral origins of H. pylori in the vast Indian subcontinent are debatable. It is not clear how different waves of human migrations in South Asia shaped the population structure of H. pylori. We tried to address these issues through mapping genetic origins of present day H. pylori in India and their genomic comparison with hundreds of isolates from different geographic regions.ResultsWe attempted to dissect genetic identity of strains by multilocus sequence typing (MLST) of the 7 housekeeping genes (atpA, efp, ureI, ppa, mutY, trpC, yphC) and phylogeographic analysis of haplotypes using MEGA and NETWORK software while incorporating DNA sequences and genotyping data of whole cag pathogenicity-islands (cagPAI). The distribution of cagPAI genes within these strains was analyzed by using PCR and the geographic type of cagA phosphorylation motif EPIYA was determined by gene sequencing. All the isolates analyzed revealed European ancestry and belonged to H. pylori sub-population, hpEurope. The cagPAI harbored by Indian strains revealed European features upon PCR based analysis and whole PAI sequencing.ConclusionThese observations suggest that H. pylori strains in India share ancestral origins with their European counterparts. Further, non-existence of other sub-populations such as hpAfrica and hpEastAsia, at least in our collection of isolates, suggest that the hpEurope strains enjoyed a special fitness advantage in Indian stomachs to out-compete any endogenous strains. These results also might support hypotheses related to gene flow in India through Indo-Aryans and arrival of Neolithic practices and languages from the Fertile Crescent.

The plasticity region of the Helicobacter pylori genome comprises strain-specific gene loci. We performed genotyping and functional biology analysis of one such locus (jhp940) that was previously found to be functionally unknown but present in gastric cancer-associated strains from many different countries. We found its geographic prevalence to be independent of cagA presence and disease status. Cloning, expression, and purification of JHP940 revealed a novel, ϳ36-kDa protein in a biologically active form which elicited strong and significant levels of tumor necrosis factor alpha and interleukin-8 in human macrophages. Also, JHP940 was able to induce enhanced translocation of the transcription factor NF-B complex in cultured macrophages. The induction of the proinflammatory cytokines by JHP940, therefore, points to its putative role in chronic gastric inflammation and, possibly, the various other outcomes of H. pylori infection, including gastric cancer.

Helicobacter pylori induces cytokine mediated changes in gastroduodenal pathophysiology, wherein, the activated macrophages at the sub-mucosal space play a central role in mounting innate immune response against the antigens. The bacterium gains niche through persistent inflammation and local immune-suppression causing peptic ulcer disease or chronic gastritis; the latter being a significant risk factor for the development of gastric adenocarcinoma. What favors persistence of H. pylori in the gastric niches is not clearly understood. We report detailed characterization of a functionally unknown gene (HP986), which was detected in patient isolates associated with peptic ulcer and gastric carcinoma. Expression and purification of recombinant HP986 (rHP986) revealed a novel, ∼29 kDa protein in biologically active form which associates with significant levels of humoral immune responses in diseased individuals (p<0.001). Also, it induced significant levels of TNF-α and Interleukin-8 in cultured human macrophages concurrent to the translocation of nuclear transcription factor-κB (NF-κB). Further, the rHP986 induced apoptosis of cultured macrophages through a Fas mediated pathway. Dissection of the underlying signaling mechanism revealed that rHP986 induces both TNFR1 and Fas expression to lead to apoptosis. We further demonstrated interaction of HP986 with TNFR1 through computational and experimental approaches. Independent proinflammatory and apoptotic responses triggered by rHP986 as shown in this study point to its role, possibly as a survival strategy to gain niche through inflammation and to counter the activated macrophages to avoid clearance.

Background. Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite of worldwide distribution. There is limited information about the seroprevalence of toxoplasmosis in the southern area of Saudi Arabia. The current study was carried out to determine the prevalence of T. gondii in pregnant women in Jazan province. Materials and Methods. The study was conducted between January and June 2013 and included 195 pregnant women, data on sociodemographic and predisposing factors were collected from each participant. Venous blood samples were collected following standard operating procedures. Serological analysis for latent toxoplasmosis (levels of IgG) and active toxoplasmosis (IgM) was done using Enzyme Linked Immunosorbent Assay (ELISA). Results. The overall seroprevalence of T. gondii in the study area was 24.1%. The seroprevalence of anti-Toxoplasma IgG was 20% (39 out of 195), whereas IgM seropositivity was 6.2% (12 out of 195). Only 4 pregnant women tested positive for both IgG and IgM. The highest IgG and IgM seroprevalence was among the study participants aged 35 to 39 years (13.5% and 35.1%, resp.). The seropositivity rate of T. gondii-specific antibodies was higher among pregnant women from the urban areas than those from rural communities (7.4% versus 0% and 21% versus 15.4% for IgM and IgG, resp.). Conclusions. The seroprevalence of T. gondii was high in pregnant woman in Jazan. The prevalence of toxoplasmosis increases with increase of age. Awareness health education program in Jazan needs to be maintained and developed to targeted pregnant women.

Helicobacter pylori cagA and vacA genotypes have been used for almost a decade as stable entities to link the severity of gastritis and ulcer disease. We describe here microevolution of the two genomic islands, cag pathogenicity island (cagPAI; 40 kb) and tfs3 (16 kb) from isolates obtained at inclusion (one subclone) and after a 10-year period (two subclones) from a duodenal ulcer patient. Our results indicate microevolution in cagA, cagE, and cag7 genes of the cagPAI and open reading frames G, P, and L in tfs3, which possibly leads to inactivation or pseudogenization of these genes. Interestingly, no significant reduction in the severity of gastroduodenal pathology was found. These results point to an obvious difficulty in correlating the continuously evolving virulence factors such as the cagPAI genes with disease characteristics that appear to remain stable.

Background: Helicobacter pylori is presumed to be co-evolved with its human host and is a highly diverse gastric pathogen at genetic levels. Ancient origins of H. pylori in the New World are still debatable. It is not clear how different waves of human migrations in South America contributed to the evolution of strain diversity of H. pylori. The objective of our 'phylogeographic' study was to gain fresh insights into these issues through mapping genetic origins of H. pylori of native Peruvians (of Amerindian ancestry) and their genomic comparison with isolates from Spain, and Japan.

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