Displaying publications 101 - 120 of 120 in total

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  1. Fulltext Graphene Oxide-Gold Nanosheets Containing Chitosan Scaffold Improves Ventricular Contractility and Function After Implantation into Infarcted Heart
    Saravanan S, Sareen N, Abu-El-Rub E, Ashour H, Sequiera GL, Ammar HI, et al.
    Sci Rep, 2018 10 10;8(1):15069.
    PMID: 30305684 DOI: 10.1038/s41598-018-33144-0
    Abnormal conduction and improper electrical impulse propagation are common in heart after myocardial infarction (MI). The scar tissue is non-conductive therefore the electrical communication between adjacent cardiomyocytes is disrupted. In the current study, we synthesized and characterized a conductive biodegradable scaffold by incorporating graphene oxide gold nanosheets (GO-Au) into a clinically approved natural polymer chitosan (CS). Inclusion of GO-Au nanosheets in CS scaffold displayed two fold increase in electrical conductivity. The scaffold exhibited excellent porous architecture with desired swelling and controlled degradation properties. It also supported cell attachment and growth with no signs of discrete cytotoxicity. In a rat model of MI, in vivo as well as in isolated heart, the scaffold after 5 weeks of implantation showed a significant improvement in QRS interval which was associated with enhanced conduction velocity and contractility in the infarct zone by increasing connexin 43 levels. These results corroborate that implantation of novel conductive polymeric scaffold in the infarcted heart improved the cardiac contractility and restored ventricular function. Therefore, our approach may be useful in planning future strategies to construct clinically relevant conductive polymer patches for cardiac patients with conduction defects.
  2. Polymorphisms in the host CYP2C19 gene and antibiotic-resistance attributes of Helicobacter pylori isolates influence the outcome of triple therapy
    Ram M R, Teh X, Rajakumar T, Goh KL, Leow AHR, Poh BH, et al.
    J Antimicrob Chemother, 2019 01 01;74(1):11-16.
    PMID: 30403784 DOI: 10.1093/jac/dky401
    Objectives: Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors.

    Methods: Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection).

    Results: Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C19*2 and CYP2C19*3 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C19*2, CYP2C19*3 and CYP2C19*17 loci. The participants heterozygous for both ABCB1 and CYP2C19*2 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects.

    Conclusions: Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.

  3. Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori
    Chua EG, Debowski AW, Webberley KM, Peters F, Lamichhane B, Loke MF, et al.
    Gastroenterol Rep (Oxf), 2019 Feb;7(1):42-49.
    PMID: 30792865 DOI: 10.1093/gastro/goy048
    Background: Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection. Hence, the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals. Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H. pylori. However, metronidazole resistance can also arise in H. pylori strains expressing functional RdxA protein, suggesting that there are other mechanisms that may confer resistance to this drug.

    Methods: We performed whole-genome sequencing on 121 H. pylori clinical strains, among which 73 were metronidazole-resistant. Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed. Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H. pylori.

    Results: Resistance due to RdxA truncation was identified in 34% of metronidazole-resistant strains. Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance. These sites included R16H/C in RdxA, D85N in the inner-membrane protein RclC (HP0565), V265I in a biotin carboxylase protein (HP0370) and A51V/T in a putative threonylcarbamoyl-AMP synthase (HP0918).

    Conclusions: Our approach identified new potential mechanisms for metronidazole resistance in H. pylori that merit further investigation.

  4. Fulltext Podoplanin Drives Motility of Active Macrophage via Regulating Filamin C During Helicobacter pylori Infection
    Cheok YY, Tan GMY, Fernandez KC, Chan YT, Lee CYQ, Cheong HC, et al.
    Front Immunol, 2021;12:702156.
    PMID: 34707599 DOI: 10.3389/fimmu.2021.702156
    Podoplanin (Pdpn) is a mucin-type transmembrane protein that has been implicated in multiple physiological settings including lymphangiogenesis, platelet aggregation, and cancer metastasis. Here, we reported an absence of Pdpn transcript expression in the resting mouse monocytic macrophages, RAW264.7 cells; intriguingly, a substantial upregulation of Pdpn was observed in activated macrophages following Helicobacter pylori or lipopolysaccharide stimulation. Pdpn-knockout macrophages demonstrated intact phagocytic and intracellular bactericidal activities comparable to wild type but exhibited impaired migration due to attenuated filopodia formation. In contrast, an ectopic expression of Pdpn augmented filopodia protrusion in activated macrophages. NanoString analysis uncovered a close dependency of Filamin C gene on the presence of Pdpn, highlighting an involvement of Filamin C in modulation of actin polymerization activity, which controls cell filopodia formation and migration. In addition, interleukin-1β production was significantly declined in the absence of Pdpn, suggesting a role of Pdpn in orchestrating inflammation during H. pylori infection besides cellular migration. Together, our findings unravel the Pdpn network that modulates movement of active macrophages.
  5. Fulltext Genomic comparison and phenotypic profiling of small colony variants of Burkholderia pseudomallei
    Zulkefli NJ, Teh CSJ, Mariappan V, Ngoi ST, Vadivelu J, Ponnampalavanar S, et al.
    PLoS One, 2021;16(12):e0261382.
    PMID: 34910764 DOI: 10.1371/journal.pone.0261382
    Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form small colony variants (SCVs) as part of the adaptive features in response to environmental stress. In this study, we characterize the genomic characteristics, antimicrobial resistance (AMR), and metabolic phenotypes of B. pseudomallei SCV and wild type (WT) strains. Whole-genome sequence analysis was performed to characterize the genomic features of two SCVs (CS and OS) and their respective parental WT strains (CB and OB). Phylogenetic relationship between the four draft genomes in this study and 19 publicly available genomes from various countries was determined. The four draft genomes showed a close phylogenetic relationship with other genomes from Southeast Asia. Broth microdilution and phenotype microarray were conducted to determine the AMR profiles and metabolic features (carbon utilization, osmolytes sensitivity, and pH conditions) of all strains. The SCV strains exhibited identical AMR phenotype with their parental WT strains. A limited number of AMR-conferring genes were identified in the B. pseudomallei genomes. The SCVs and their respective parental WT strains generally shared similar carbon-utilization profiles, except for D,L-carnitine (CS), g-hydroxybutyric acid (OS), and succinamic acid (OS) which were utilized by the SCVs only. No difference was observed in the osmolytes sensitivity of all strains. In comparison, WT strains were more resistant to alkaline condition, while SCVs showed variable growth responses at higher acidity. Overall, the genomes of the colony morphology variants of B. pseudomallei were largely identical, and the phenotypic variations observed among the different morphotypes were strain-specific.
  6. Helicobacter pylori outer inflammatory protein A (OipA) suppresses apoptosis of AGS gastric cells in vitro
    Al-Maleki AR, Loke MF, Lui SY, Ramli NSK, Khosravi Y, Ng CG, et al.
    Cell. Microbiol., 2017 12;19(12).
    PMID: 28776327 DOI: 10.1111/cmi.12771
    Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA "on" and "off" motifs. Proteomics analysis was performed on AGS cell pre-infection and postinfection with H. pylori oipA "on" and "off" strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down-regulated postinfection with oipA "off" strains comparing to oipA "on" strains. Furthermore, oipA "off" and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell-cycle arrest than oipA "on" strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of H. pylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA "on" strains predominates.
  7. Increased frequency of late-senescent T cells lacking CD127 in chronic hepatitis C disease
    Barathan M, Mohamed R, Saeidi A, Vadivelu J, Chang LY, Gopal K, et al.
    Eur J Clin Invest, 2015 May;45(5):466-74.
    PMID: 25721991 DOI: 10.1111/eci.12429
    Hepatitis C virus (HCV) causes persistent disease in ~85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses.
  8. Fulltext Knowledge, attitude and practice on dengue prevention and dengue seroprevalence in a dengue hotspot in Malaysia: A cross-sectional study
    Selvarajoo S, Liew JWK, Tan W, Lim XY, Refai WF, Zaki RA, et al.
    Sci Rep, 2020 Jun 12;10(1):9534.
    PMID: 32533017 DOI: 10.1038/s41598-020-66212-5
    Dengue has become a global public health problem. Despite reactive efforts by the government in Malaysia, the dengue cases are on the increase. Adequate knowledge, positive attitude and correct practice for dengue control are essential to stamp out the disease. Hence, this study aims to assess the factors associated with dengue knowledge, attitude and practice (KAP), as well as the association with dengue IgM and IgG seropositivity. A community-based cross-sectional study was conducted in a closed, dengue endemic area with multi-storey dwellings . Five hundred individuals (aged 18 years and above) were approached for pre-tested KAP and seroprevalences assessment. The study showed only half of the total participants have good knowledge (50.7%) but they had insufficient knowledge about dengue during pregnancy. 53.2% of people had poor attitude and 50.2% reported poor practice for dengue control. Out of 85 respondents who agreed to participate in the dengue seroprevalence study, 74.1% (n = 63) were positive for dengue IgG and 7.1% (n = 6) were positive for dengue IgM. Among all sociodemographic variable, race is the only independent predicator for all KAP levels (P 
  9. Fulltext The complete methylome of Helicobacter pylori UM032
    Lee WC, Anton BP, Wang S, Baybayan P, Singh S, Ashby M, et al.
    BMC Genomics, 2015;16:424.
    PMID: 26031894 DOI: 10.1186/s12864-015-1585-2
    The genome of the human gastric pathogen Helicobacter pylori encodes a large number of DNA methyltransferases (MTases), some of which are shared among many strains, and others of which are unique to a given strain. The MTases have potential roles in the survival of the bacterium. In this study, we sequenced a Malaysian H. pylori clinical strain, designated UM032, by using a combination of PacBio Single Molecule, Real-Time (SMRT) and Illumina MiSeq next generation sequencing platforms, and used the SMRT data to characterize the set of methylated bases (the methylome).
  10. Retraction Note: Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity
    Sidahmed HMA, Azizan AHS, Mohan S, Abdulla MA, Abdelwahab SI, Taha MME, et al.
    BMC Complement Med Ther, 2024 Apr 19;24(1):166.
    PMID: 38641576 DOI: 10.1186/s12906-024-04475-5
  11. Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes
    Barathan M, Gopal K, Mohamed R, Ellegård R, Saeidi A, Vadivelu J, et al.
    Apoptosis, 2015 Apr;20(4):466-80.
    PMID: 25577277 DOI: 10.1007/s10495-014-1084-y
    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.
  12. 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.
  13. Fulltext Erratum: Author Correction: High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia
    Drewes JL, White JR, Dejea CM, Fathi P, Iyadorai T, Vadivelu J, et al.
    NPJ Biofilms Microbiomes, 2019 01 09;5(1):2.
    PMID: 30652010 DOI: 10.1038/s41522-018-0078-x
    [This corrects the article DOI: 10.1038/s41522-017-0040-3.].
  14. Fulltext Comparing the genomes of Helicobacter pylori clinical strain UM032 and Mice-adapted derivatives
    Khosravi Y, Rehvathy V, Wee WY, Wang S, Baybayan P, Singh S, et al.
    Gut Pathog, 2013;5:25.
    PMID: 23957912 DOI: 10.1186/1757-4749-5-25
    Helicobacter pylori is a Gram-negative bacterium that persistently infects the human stomach inducing chronic inflammation. The exact mechanisms of pathogenesis are still not completely understood. Although not a natural host for H. pylori, mouse infection models play an important role in establishing the immunology and pathogenicity of H. pylori. In this study, for the first time, the genome sequences of clinical H. pylori strain UM032 and mice-adapted derivatives, 298 and 299, were sequenced using the PacBio Single Molecule, Real-Time (SMRT) technology.
  15. Fulltext Assessment of Risk and Sero-Prevalence of Helicobacter pylori Colonization among Remote Orang Asli Tribes in Peninsula Malaysia
    Thevakumar K, Chandren JR, Perez-Perez GI, Chua EG, Teh LK, Salleh MZ, et al.
    PLoS One, 2016;11(7):e0159830.
    PMID: 27441568 DOI: 10.1371/journal.pone.0159830
    The epidemiology of Helicobacter pylori (H. pylori) infection is related to human poverty with marked differences between developing and developed countries. Socioeconomic factors and living standards are the main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. The aim of this study was to assess the risk and sero-prevalence of H. pylori colonization among Orang Asli in Peninsula Malaysia. This cross-sectional study was conducted on Orang Asli subjects in seven isolated settlements spanning across all three major tribes (Negrito, Proto Malay and Senoi) in Malaysia. Socio-demographic characteristics of the subjects were obtained through interview. Subjects were tested for H. pylori colonization based on CagA and whole cell (WC) antigen serological assays. A total of 275 subjects participated in this study. Among these subjects, 115 (44.7%) were H. pylori sero-positive with highest sero-prevalence among Negrito (65.7%). Among subjects who were H. pylori sero-positive, CagA sero positivity was also significantly higher among Negrito. The highest proportion of respondents reported to be H. pylori sero-positive was from age group 30 years old and below (57.9%), males (56.2%), Negrito (48.6%) and live in bamboo house (92.3%). The highest proportion of respondents reported to be CagA sero-positive was from age group 30 years old and below (41.4%), males (35.6%) and Negrito (48.6%). The results of this study demonstrate that H. pylori colonization can be related to age, gender, tribes and house materials and CagA sero-positive stain closely associated with age, gender and tribes.
  16. Fulltext Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection
    Yong YK, Saeidi A, Tan HY, Rosmawati M, Enström PF, Batran RA, et al.
    Front Immunol, 2018;9:472.
    PMID: 29616020 DOI: 10.3389/fimmu.2018.00472
    Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.
  17. Fulltext Genomic structure and insertion sites of Helicobacter pylori prophages from various geographical origins
    Vale FF, Nunes A, Oleastro M, Gomes JP, Sampaio DA, Rocha R, et al.
    Sci Rep, 2017 02 16;7:42471.
    PMID: 28205536 DOI: 10.1038/srep42471
    Helicobacter pylori genetic diversity is known to be influenced by mobile genomic elements. Here we focused on prophages, the least characterized mobile elements of H. pylori. We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found in H. pylori isolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The genome sizes of these prophages range from 22.6-33.0 Kbp, consisting of 27-39 open reading frames. A 36.6% GC was found in prophages in contrast to 39% in H. pylori genome. Remarkably a conserved integration site was found in over 50% of the cases. Nearly 40% of the prophages harbored insertion sequences (IS) previously described in H. pylori. Tandem repeats were frequently found in the intergenic region between the prophage at the 3' end and the bacterial gene. Furthermore, prophage genomes present a robust phylogeographic pattern, revealing four distinct clusters: one African, one Asian and two European prophage populations. Evidence of recombination was detected within the genome of some prophages, resulting in genome mosaics composed by different populations, which may yield additional H. pylori phenotypes.
  18. Fulltext High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia
    Drewes JL, White JR, Dejea CM, Fathi P, Iyadorai T, Vadivelu J, et al.
    NPJ Biofilms Microbiomes, 2017;3:34.
    PMID: 29214046 DOI: 10.1038/s41522-017-0040-3
    Colorectal cancer (CRC) remains the third most common cancer worldwide, with a growing incidence among young adults. Multiple studies have presented associations between the gut microbiome and CRC, suggesting a link with cancer risk. Although CRC microbiome studies continue to profile larger patient cohorts with increasingly economical and rapid DNA sequencing platforms, few common associations with CRC have been identified, in part due to limitations in taxonomic resolution and differences in analysis methodologies. Complementing these taxonomic studies is the newly recognized phenomenon that bacterial organization into biofilm structures in the mucus layer of the gut is a consistent feature of right-sided (proximal), but not left-sided (distal) colorectal cancer. In the present study, we performed 16S rRNA gene amplicon sequencing and biofilm quantification in a new cohort of patients from Malaysia, followed by a meta-analysis of eleven additional publicly available data sets on stool and tissue-based CRC microbiota using Resphera Insight, a high-resolution analytical tool for species-level characterization. Results from the Malaysian cohort and the expanded meta-analysis confirm that CRC tissues are enriched for invasive biofilms (particularly on right-sided tumors), a symbiont with capacity for tumorigenesis (Bacteroides fragilis), and oral pathogens including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus stomatis. Considered in aggregate, species from the Human Oral Microbiome Database are highly enriched in CRC. Although no detected microbial feature was universally present, their substantial overlap and combined prevalence supports a role for the gut microbiota in a significant percentage (>80%) of CRC cases.
  19. Draft genome sequences of Helicobacter pylori isolates from Malaysia, cultured from patients with functional dyspepsia and gastric cancer
    Gunaletchumy SP, Teh X, Khosravi Y, Ramli NS, Chua EG, Kavitha T, et al.
    J Bacteriol, 2012 Oct;194(20):5695-6.
    PMID: 23012278
    Helicobacter pylori is the main bacterial causative agent of gastroduodenal disorders and a risk factor for gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. The draft genomes of 10 closely related H. pylori isolates from the multiracial Malaysian population will provide an insight into the genetic diversity of isolates in Southeast Asia. These isolates were cultured from gastric biopsy samples from patients with functional dyspepsia and gastric cancer. The availability of this genomic information will provide an opportunity for examining the evolution and population structure of H. pylori isolates from Southeast Asia, where the East meets the West.
  20. Fulltext Microbiota organization is a distinct feature of proximal colorectal cancers
    Dejea CM, Wick EC, Hechenbleikner EM, White JR, Mark Welch JL, Rossetti BJ, et al.
    Proc Natl Acad Sci U S A, 2014 Dec 23;111(51):18321-6.
    PMID: 25489084 DOI: 10.1073/pnas.1406199111
    Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.
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