MyMedR

Fulltext Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution

Kumar N, Mariappan V, Baddam R, Lankapalli AK, Shaik S, Goh KL, et al.

Nucleic Acids Res, 2015 Jan;43(1):324-35.

PMID: 25452339 DOI: 10.1093/nar/gku1271

The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host-pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner.

Matched MeSH terms: Helicobacter pylori/genetics*

The use of the resonant mirror biosensor to detect point mutations, as demonstrated with synthetic oligonucleotides

Momynaliev KT, Govorun VM, Gnedenko O, Ivanov YD, Archakov AI

J. Mol. Recognit., 2003 Jan-Feb;16(1):1-8.

PMID: 12557232

The possibility of using the resonant mirror biosensor to detect point substitutions in oligonucleotides was demonstrated with a fragment of the Helicobacter pylori 23S rRNA gene, point mutations in which are responsible for clarythromycin resistance. Conditions were optimized for the interaction of a probe immobilized on the sensing surface with targets containing various nucleotide substitutions. A probe allowing reliable discrimination of mutant targets was selected. The mismatch position in the probe was shown to affect the kinetic parameters (response) of hybridization with mutant targets, reporting not only the position, but also the character (G or C) of a substitution.

Matched MeSH terms: Helicobacter pylori/genetics

Fulltext Helicobacter pylori and gastric cancer: Indian enigma

Misra V, Pandey R, Misra SP, Dwivedi M

World J Gastroenterol, 2014 Feb 14;20(6):1503-9.

PMID: 24587625 DOI: 10.3748/wjg.v20.i6.1503

Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.

Matched MeSH terms: Helicobacter pylori/genetics*

Fulltext Functional and molecular surveillance of Helicobacter pylori antibiotic resistance in Kuala Lumpur

Teh X, Khosravi Y, Lee WC, Leow AH, Loke MF, Vadivelu J, et al.

PLoS One, 2014;9(7):e101481.

PMID: 25003707 DOI: 10.1371/journal.pone.0101481

Helicobacter pylori is the etiological agent for diseases ranging from chronic gastritis and peptic ulcer disease to gastric adenocarcinoma and primary gastric B-cell lymphoma. Emergence of resistance to antibiotics possesses a challenge to the effort to eradicate H. pylori using conventional antibiotic-based therapies. The molecular mechanisms that contribute to the resistance of these strains have yet to be identified and are important for understanding the evolutional pattern and selective pressure imposed by the environment.

Matched MeSH terms: Helicobacter pylori/genetics*

Clarithromycin resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Malaysia

Ho SL, Tan EL, Sam CK, Goh KL

J Dig Dis, 2010 Apr;11(2):101-5.

PMID: 20402836 DOI: 10.1111/j.1751-2980.2010.00423.x

To determine the prevalence of primary clarithromycin resistance amongst Helicobacter pylori (H. pylori) strains in Malaysian patients with gastroduodenal diseases, by using restriction fragment length polymorphism (RFLP) in domain V of 23S rRNA.

Matched MeSH terms: Helicobacter pylori/genetics*

Role of Helicobacter pylori virulence factor and genotypes in non-ulcer dyspepsia

Tan HJ, Rizal AM, Rosmadi MY, Goh KL

J Gastroenterol Hepatol, 2006 Jan;21(1 Pt 1):110-5.

PMID: 16706821

The role of Helicobacter pylori (HP) in non-ulcer dyspepsia is debatable. Eradicating HP will help a small group of non-ulcer dyspeptic patients. However, it is unclear which subgroup of patients will benefit from eradication therapy. The aim of the present study was to compare the cagA and cagE status, as well as vacA genotypes, of HP in non-ulcer dyspeptic patients who responded successfully to eradication therapy compared with those patients who did not.

Matched MeSH terms: Helicobacter pylori/genetics*

Distribution of Helicobacter pylori cagA, cagE and vacA in different ethnic groups in Kuala Lumpur, Malaysia

Tan HJ, Rizal AM, Rosmadi MY, Goh KL

J Gastroenterol Hepatol, 2005 Apr;20(4):589-94.

PMID: 15836708

There is a geographic variation in Helicobacter pylori (HP) genotypes and virulence factors. Cytotoxin associated genes A (cagA) and E (cagE), and certain vacuolating cytotoxin (vacA) genotypes are associated with peptic ulcer disease (PUD). There is also a different prevalence of PUD among different ethnic groups in Malaysia. The present study compared the distribution of vacA alleles and cagA and cagE status in three ethnic groups residing in Kuala Lumpur, Malaysia, and their association with clinical outcome.

Matched MeSH terms: Helicobacter pylori/genetics*

Fulltext Understanding the dimorphic lifestyles of human gastric pathogen Helicobacter pylori using the SWATH-based proteomics approach

Loke MF, Ng CG, Vilashni Y, Lim J, Ho B

Sci Rep, 2016 05 25;6:26784.

PMID: 27222005 DOI: 10.1038/srep26784

Helicobacter pylori may reside in the human stomach as two morphological forms: the culturable spiral form and the viable but non-culturable (VBNC) coccoid form. This bacterium transforms from spiral to coccoid under in vitro suboptimal conditions. However, both spiral and coccoid have demonstrated its infectivity in laboratory animals, suggesting that coccoid may potentially be involved in the transmission of H. pylori. To determine the relevance of the coccoid form in viability and infectivity, we compared the protein profiles of H. pylori coccoids obtained from prolonged (3-month-old) culture with that of 3-day-old spirals of two H. pylori standard strains using SWATH (Sequential Window Acquisition of all Theoretical mass spectra)-based approach. The protein profiles reveal that the coccoids retained basal level of metabolic proteins and also high level of proteins that participate in DNA replication, cell division and biosynthesis demonstrating that coccoids are viable. Most interestingly, these data also indicate that the H. pylori coccoids possess higher level of proteins that are involved in virulence and carcinogenesis than their spiral counterparts. Taken together, these findings have important implications in the understanding on the pathogenesis of H. pylori-induced gastroduodenal diseases, as well as the probable transmission mode of this bacterium.

Matched MeSH terms: Helicobacter pylori/genetics

Association of Malaysian Helicobacter pylori virulence polymorphisms with severity of gastritis and patients' ethnicity

Alfizah H, Ramelah M, Rizal AM, Anwar AS, Isa MR

Helicobacter, 2012 Oct;17(5):340-9.

PMID: 22967117 DOI: 10.1111/j.1523-5378.2012.00956.x

Polymorphisms of Helicobacter pylori cagA and vacA genes do exist and may contribute to differences in H. pylori infection and gastroduodenal diseases among races in the Malaysian population. This study was conducted to characterize the polymorphisms in H. pylori cagA and vacA in Malaysian population.

Matched MeSH terms: Helicobacter pylori/genetics*

Helicobacter pylori, ethnicity, and the gastroesophageal reflux disease spectrum: a study from the East

Rajendra S, Ackroyd R, Robertson IK, Ho JJ, Karim N, Kutty KM

Helicobacter, 2007 Apr;12(2):177-83.

PMID: 17309756

Ethnic differences in gastroesophageal reflux disease (GERD) and its complications as well as racial variations in the prevalence of Helicobacter pylori infection are well documented. Nevertheless, the association between reflux disease, H. pylori, and race has not been adequately explored.

Matched MeSH terms: Helicobacter pylori/genetics

Fulltext Reductive evolution in outer membrane protein biogenesis has not compromised cell surface complexity in Helicobacter pylori

Webb CT, Chandrapala D, Oslan SN, Bamert RS, Grinter RD, Dunstan RA, et al.

Microbiologyopen, 2017 12;6(6).

PMID: 29055967 DOI: 10.1002/mbo3.513

Helicobacter pylori is a gram-negative bacterial pathogen that chronically inhabits the human stomach. To survive and maintain advantage, it has evolved unique host-pathogen interactions mediated by Helicobacter-specific proteins in the bacterial outer membrane. These outer membrane proteins (OMPs) are anchored to the cell surface via a C-terminal β-barrel domain, which requires their assembly by the β-barrel assembly machinery (BAM). Here we have assessed the complexity of the OMP C-terminal β-barrel domains employed by H. pylori, and characterized the H. pyloriBAM complex. Around 50 Helicobacter-specific OMPs were assessed with predictive structural algorithms. The data suggest that H. pylori utilizes a unique β-barrel architecture that might constitute H. pylori-specific Type V secretions system. The structural and functional diversity in these proteins is encompassed by their extramembrane domains. Bioinformatic and biochemical characterization suggests that the low β-barrel-complexity requires only minimalist assembly machinery. The H. pylori proteins BamA and BamD associate to form a BAM complex, with features of BamA enabling an oligomerization that might represent a mechanism by which a minimalist BAM complex forms a larger, sophisticated machinery capable of servicing the outer membrane proteome of H. pylori.

Matched MeSH terms: Helicobacter pylori/genetics

Fulltext Population structure of Helicobacter pylori among ethnic groups in Malaysia: recent acquisition of the bacterium by the Malay population

Tay CY, Mitchell H, Dong Q, Goh KL, Dawes IW, Lan R

BMC Microbiol, 2009;9:126.

PMID: 19538757 DOI: 10.1186/1471-2180-9-126

Helicobacter pylori is a major gastric bacterial pathogen. This pathogen has been shown to follow the routes of human migration by their geographical origin and currently the global H. pylori population has been divided into six ancestral populations, three from Africa, two from Asia and one from Europe. Malaysia is made up of three major ethnic populations, Malay, Chinese and Indian, providing a good population for studying recent H. pylori migration and admixture.

Matched MeSH terms: Helicobacter pylori/genetics

Fulltext Helicobacter pylori vacA as marker for gastric cancer and gastroduodenal diseases: one but not the only factor

Abadi AT, Lee YY

J Clin Microbiol, 2014 Dec;52(12):4451.

PMID: 25399000 DOI: 10.1128/JCM.02640-14

Matched MeSH terms: Helicobacter pylori/genetics*

Fulltext Evolutionary history of Helicobacter pylori sequences reflect past human migrations in Southeast Asia

Breurec S, Guillard B, Hem S, Brisse S, Dieye FB, Huerre M, et al.

PLoS One, 2011;6(7):e22058.

PMID: 21818291 DOI: 10.1371/journal.pone.0022058

The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia.

Matched MeSH terms: Helicobacter pylori/genetics*

Fulltext Comparative Genomics Revealed Multiple Helicobacter pylori Genes Associated with Biofilm Formation In Vitro

Wong EH, Ng CG, Chua EG, Tay AC, Peters F, Marshall BJ, et al.

PLoS One, 2016;11(11):e0166835.

PMID: 27870886 DOI: 10.1371/journal.pone.0166835

BACKGROUND: Biofilm formation by Helicobacter pylori may be one of the factors influencing eradication outcome. However, genetic differences between good and poor biofilm forming strains have not been studied.

MATERIALS AND METHODS: Biofilm yield of 32 Helicobacter pylori strains (standard strain and 31 clinical strains) were determined by crystal-violet assay and grouped into poor, moderate and good biofilm forming groups. Whole genome sequencing of these 32 clinical strains was performed on the Illumina MiSeq platform. Annotation and comparison of the differences between the genomic sequences were carried out using RAST (Rapid Annotation using Subsystem Technology) and SEED viewer. Genes identified were confirmed using PCR.

RESULTS: Genes identified to be associated with biofilm formation in H. pylori includes alpha (1,3)-fucosyltransferase, flagellar protein, 3 hypothetical proteins, outer membrane protein and a cag pathogenicity island protein. These genes play a role in bacterial motility, lipopolysaccharide (LPS) synthesis, Lewis antigen synthesis, adhesion and/or the type-IV secretion system (T4SS). Deletion of cagA and cagPAI confirmed that CagA and T4SS were involved in H. pylori biofilm formation.

CONCLUSIONS: Results from this study suggest that biofilm formation in H. pylori might be genetically determined and might be influenced by multiple genes. Good, moderate and poor biofilm forming strain might differ during the initiation of biofilm formation.

Matched MeSH terms: Helicobacter pylori/genetics

cagA gene variants in Malaysian Helicobacter pylori strains isolated from patients of different ethnic groups

Ramelah M, Aminuddin A, Alfizah H, Isa MR, Jasmi AY, Tan HJ, et al.

FEMS Immunol. Med. Microbiol., 2005 May 1;44(2):239-42.

PMID: 15866222

Helicobacter pylori infection of a distinct subtype of cagA may lead to different pathological manifestation. The aim of this study is to determine the presence of cagA gene and its variants in H. pylori infection among different ethnic groups and its effect on gastroduodenal diseases. Overall detection of cagA among the 205 clinical isolates of H. pylori was 94%. Variations in size of the 3' region of cagA gene were examined among 192 Malaysian H. pylori cagA-positive strains. Results showed that three cagA variants differing in fragment length of PCR products were detected and designated as type A (621-651bp), type B (732-735bp) and type C (525 bp). Although there was no association between any of the cagA subtypes with peptic ulcer disease (p>0.05), an association between cagA subtypes with a specific ethnic group was observed. Specific-cagA subtype A strains were predominantly isolated from Chinese compared to Malays and Indians (p<0.0005), and cagA subtype B strains were predominantly isolated from Malays and Indians compared to Chinese (p<0.05). The cagA type A strains of H. pylori is commonly found in the Chinese patients who have a higher risk of peptic ulcer disease, thus indicating that it could be used as an important clinical biomarker for a more severe infection.

Matched MeSH terms: Helicobacter pylori/genetics

Molecular Detection of Helicobacter pylori and its Antimicrobial Resistance in Brazzaville, Congo

Ontsira Ngoyi EN, Atipo Ibara BI, Moyen R, Ahoui Apendi PC, Ibara JR, Obengui O, et al.

Helicobacter, 2015 Aug;20(4):316-20.

PMID: 25585658 DOI: 10.1111/hel.12204

Helicobacter pylori infection is involved in several gastroduodenal diseases which can be cured by antimicrobial treatment. The aim of this study was to determine the prevalence of H. pylori infection and its bacterial resistance to clarithromycin, fluoroquinolones, and tetracycline in Brazzaville, Congo, by using molecular methods.

Matched MeSH terms: Helicobacter pylori/genetics

Distinct cagA EPIYA motifs are associated with ethnic diversity in Malaysia and Singapore

Schmidt HM, Goh KL, Fock KM, Hilmi I, Dhamodaran S, Forman D, et al.

Helicobacter, 2009 Aug;14(4):256-63.

PMID: 19674129 DOI: 10.1111/j.1523-5378.2009.00684.x

In vitro studies have shown that the biologic activity of CagA is influenced by the number and class of EPIYA motifs present in its variable region as these motifs correspond to the CagA phosphorylation sites. It has been hypothesized that strains possessing specific combinations of these motifs may be responsible for gastric cancer development. This study investigated the prevalence of cagA and the EPIYA motifs with regard to number, class, and patterns in strains from the three major ethnic groups within the Malaysian and Singaporean populations in relation to disease development.

Matched MeSH terms: Helicobacter pylori/genetics*

The cag PAI is intact and functional but HP0521 varies significantly in Helicobacter pylori isolates from Malaysia and Singapore

Schmidt HM, Andres S, Nilsson C, Kovach Z, Kaakoush NO, Engstrand L, et al.

Eur J Clin Microbiol Infect Dis, 2010 Apr;29(4):439-51.

PMID: 20157752 DOI: 10.1007/s10096-010-0881-7

Helicobacter pylori-related disease is at least partially attributable to the genotype of the infecting strain, particularly the presence of specific virulence factors. We investigated the prevalence of a novel combination of H. pylori virulence factors, including the cag pathogenicity island (PAI), and their association with severe disease in isolates from the three major ethnicities in Malaysia and Singapore, and evaluated whether the cag PAI was intact and functional in vitro. Polymerase chain reaction (PCR) was used to detect dupA, cagA, cagE, cagT, cagL and babA, and to type vacA, the EPIYA motifs, HP0521 alleles and oipA ON status in 159 H. pylori clinical isolates. Twenty-two strains were investigated for IL-8 induction and CagA translocation in vitro. The prevalence of cagA, cagE, cagL, cagT, babA, oipA ON and vacA s1 and i1 was >85%, irrespective of the disease state or ethnicity. The prevalence of dupA and the predominant HP0521 allele and EPIYA motif varied significantly with ethnicity (p < 0.05). A high prevalence of an intact cag PAI was found in all ethnic groups; however, no association was observed between any virulence factor and disease state. The novel association between the HP0521 alleles, EPIYA motifs and host ethnicity indicates that further studies to determine the function of this gene are important.

Matched MeSH terms: Helicobacter pylori/genetics*

Fulltext Helicobacter pylori recombinant UreG protein: cloning, expression, and assessment of its seroreactivity

Khalilpour A, Osman S, Yunus MH, Santhanam A, Vellasamy N, Noordin R

BMC Res Notes, 2014;7:809.

PMID: 25406411 DOI: 10.1186/1756-0500-7-809

Helicobacter pylori is a human pathogen and during the process of infection, antigens from the bacterium elicit strong host humoral immune responses. In our previous report, native H. pylori UreG protein showed good reactivity with sera from H. pylori patients. This study was aimed at producing the recombinant form of the protein (rUreG) and determining its seroreactivities.

Matched MeSH terms: Helicobacter pylori/genetics*

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