Comparative genomics of <it>Helicobacter pylori </it>isolates recovered from ulcer disease patients in England

<p>Abstract</p> <p>Background</p> <p>Genomic diversity of <it>H. pylori </it>from many different human populations is largely unknown. We compared genomes of 65 <it>H. pylori </it>strains from Nottingham, England. Molecular analysis was carried out to identify rearrangements within and outside the <it>cag</it>-pathogenicity-island (<it>cag </it>PAI) and DNA sequence divergence in candidate genes. Phylogenetic analysis was carried out based on various high-resolution genotyping techniques.</p> <p>Results</p> <p>Analyses of virulence genes (<it>cag</it>T, <it>cag</it>E, <it>cag</it>A, <it>vac</it>A, <it>ice</it>A, <it>oip</it>A and <it>bab</it>B) revealed that <it>H. pylori </it>strains from England are genetically distinct from strains obtained from other countries. The toxigenic <it>vac</it>A s1m1 genotype was found to be less common and the plasticity region cluster was found to be disrupted in all the isolates. English isolates showed a predominance of <it>ice</it>A1 alleles and a functional proinflammatory <it>oip</it>A gene. The English <it>H. pylori </it>gene pool revealed several Asian/oriental features. This included the predominance of <it>cag</it>A – <it>glr </it>(<it>cag</it>A right junction) motif types III and II (up to 42%), presence of <it>vac</it>A m1c alleles and phylogenetic affinity towards East Asian / Amerindian gene pools based on fluorescent amplified fragment length polymorphism (FAFLP) analysis and <it>glm</it>M sequence analysis.</p> <p>Conclusion</p> <p>Overall, our results demonstrated genetic affinities of <it>H. pylori </it>in England with both European and the Asian gene pools and some distinctive genetic features of virulence genes that may have evolved in this important European population.</p

<i>AmpliBASE</i> MT^TM: a <i>Mycobacterium tuberculosis</i> diversity knowledgebase

AmpliBASE MTTM is an online databank of high-resolution DNA fingerprints representing fluorescent amplified fragment length polymorphism (FAFLP) profiles or amplitypes developed for the Mycobacterium tuberculosis complex strains from 48 different countries. AmpliBASE MTTM is based on a relational database management system that is hyperlinked to visualize genotyping results in the form of DNA fingerprint images for individual strains. A flexible search system based on systematic comparisons of fragment sizes in base pairs allows inter-laboratory comparison of FAFLP profiles. Besides this, the database also displays previously published data on IS6110 profiles, spoligotypes, MIRU-VNTRs and large sequence polymorphisms along with the FAFLP records that will give the overall comparisons. Being the first of its kind, AmpliBASE MTTM is expected to be a very helpful tool in strengthening the concept of ‘geographic genomics’ and will be very helpful to molecular epidemiologists and those interested in diagnostic development for tuberculosis

The cag Pathogenicity Island of Helicobacter pylori Is Disrupted in the Majority of Patient Isolates from Different Human Populations

The cag pathogenicity island (cag-PAI) is one of the major virulence determinants of Helicobacter pylori. The chromosomal integrity of this island or the lack thereof is speculated to play an important role in the progress of the gastroduodenal pathology caused by H. pylori. We determined the integrity of the cag-PAI by using specific flanking and internally anchored PCR primers to know the biogeographical distribution of strains carrying fully integral cag-PAI with proinflammatory behavior in vivo. Genotypes based on eight selected loci were studied in 335 isolates obtained from eight different geographic regions. The cag-PAI appeared to be disrupted in the majority of patient isolates throughout the world. Conservation of cag-PAI was highest in Japanese isolates (57.1%). However, only 18.6% of the Peruvian and 12% of the Indian isolates carried an intact cag-PAI. The integrity of cag-PAI in European and African strains was minimal. All 10 strains from Costa Rica had rearrangements. Overall, a majority of the strains of East Asian ancestry were found to have intact cag-PAI compared to strains of other descent. We also found that the cagE and cagT genes were less often rearranged (18%) than the cagA gene (27%). We attempted to relate cag-PAI rearrangement patterns to disease outcome. Deletion frequencies of cagA, cagE, and cagT genes were higher in benign cases than in isolates from severe ulcers and gastric cancer. Conversely, the cagA promoter and the left end of the cag-PAI were frequently rearranged or deleted in isolates linked to severe pathology. Analysis of the cag-PAI genotypes with a different biogeoclimatic history will contribute to our understanding of the pathogen-host interaction in health and disease

The <i>cag</i> pathogenicity island of <i>Helicobacter pylori</i> is disrupted in the majority of patient isolates from different human populations

The cag pathogenicity island (cag-PAI) is one of the major virulence determinants of Helicobacter pylori. The chromosomal integrity of this island or the lack thereof is speculated to play an important role in the progress of the gastroduodenal pathology caused by H. pylori. We determined the integrity of the cag-PAI by using specific flanking and internally anchored PCR primers to know the biogeographical distribution of strains carrying fully integral cag-PAI with proinflammatory behavior in vivo. Genotypes based on eight selected loci were studied in 335 isolates obtained from eight different geographic regions. The cag-PAI appeared to be disrupted in the majority of patient isolates throughout the world. Conservation of cag-PAI was highest in Japanese isolates (57.1%). However, only 18.6% of the Peruvian and 12% of the Indian isolates carried an intact cag-PAI. The integrity of cag-PAI in European and African strains was minimal. All 10 strains from Costa Rica had rearrangements. Overall, a majority of the strains of East Asian ancestry were found to have intact cag-PAI compared to strains of other descent. We also found that the cagE and cagT genes were less often rearranged (18%) than the cagA gene (27%). We attempted to relate cag-PAI rearrangement patterns to disease outcome. Deletion frequencies of cagA, cagE, and cagT genes were higher in benign cases than in isolates from severe ulcers and gastric cancer. Conversely, the cagA promoter and the left end of the cag-PAI were frequently rearranged or deleted in isolates linked to severe pathology. Analysis of the cag-PAI genotypes with a different biogeoclimatic history will contribute to our understanding of the pathogen-host interaction in health and disease

Molecular Genotyping of a Large, Multicentric Collection of Tubercle Bacilli Indicates Geographical Partitioning of Strain Variation and Has Implications for Global Epidemiology of Mycobacterium tuberculosis

Tuberculosis continues to be a major killer disease, despite an all-out effort launched against it in the postgenomic era. We describe here the population structure of Mycobacterium tuberculosis strains, as revealed by a chromosome-wide scan of fluorescent amplified fragment length polymorphisms (FAFLPs), for more than 1,100 independent isolates from 11 different countries. The bacterial strains were genotyped based on a total of 136 ± 1 different FAFLP markers at the genome sequence interface, with details on IS6110 profiles, drug resistance status, clinicopathological observations, and host status integrated into the analysis process. The strains were found to cluster with possible geographic affinities, including the parameters of host species type, IS6110 profile, and drug susceptibility status. Of the five most commonly amplified fragment sets (or amplitypes), type A predominated in strains of mixed origin, deposited in The Netherlands; type B was exclusively observed for Indian isolates; type C was found mainly in strains from Peru and Australia; and types D and E predominated in European strains from France and Italy. The amplitypes were independent of certain large sequence polymorphisms representing two important deletions, TbD1 and Rd9. It appears that M. tuberculosis has a high genomic diversity with a possible geographic evolution. This may have occurred due to specific genomic deletions and synonymous substitutions selected rigorously against host defenses and environmental stresses on an evolutionary timescale. The genotypic data reported here are additionally significant for genotype-phenotype correlations and for determining whether pathogen diversity is a reflection f the host population diversity