Displaying publications 1 - 20 of 59 in total

Abstract:
Sort:
  1. 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.
  2. 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).
  3. Tan GM, Looi CY, Fernandez KC, Vadivelu J, Loke MF, Wong WF
    Sci Rep, 2015;5:11046.
    PMID: 26078204 DOI: 10.1038/srep11046
    Helicobacter pylori at multiplicity of infection (MOI ≥ 50) have been shown to cause apoptosis in RAW264.7 monocytic macrophage cells. Because chronic gastric infection by H. pylori results in the persistence of macrophages in the host's gut, it is likely that H. pylori is present at low to moderate, rather than high numbers in the infected host. At present, the effect of low-MOI H. pylori infection on macrophage has not been fully elucidated. In this study, we investigated the genome-wide transcriptional regulation of H. pylori-infected RAW264.7 cells at MOI 1, 5 and 10 in the absence of cellular apoptosis. Microarray data revealed up- and down-regulation of 1341 and 1591 genes, respectively. The expression of genes encoding for DNA replication and cell cycle-associated molecules, including Aurora-B kinase (AurkB) were down-regulated. Immunoblot analysis verified the decreased expression of AurkB and downstream phosphorylation of Cdk1 caused by H. pylori infection. Consistently, we observed that H. pylori infection inhibited cell proliferation and progression through the G1/S and G2/M checkpoints. In summary, we suggest that H. pylori disrupts expression of cell cycle-associated genes, thereby impeding proliferation of RAW264.7 cells, and such disruption may be an immunoevasive strategy utilized by H. pylori.
  4. Khosravi Y, Dieye Y, Loke MF, Goh KL, Vadivelu J
    PLoS One, 2014;9(11):e112214.
    PMID: 25386948 DOI: 10.1371/journal.pone.0112214
    Helicobacter pylori (H. pylori) is a major gastric pathogen that has been associated with humans for more than 60,000 years. H. pylori causes different gastric diseases including dyspepsia, ulcers and gastric cancers. Disease development depends on several factors including the infecting H. pylori strain, environmental and host factors. Another factor that might influence H. pylori colonization and diseases is the gastric microbiota that was overlooked for long because of the belief that human stomach was a hostile environment that cannot support microbial life. Once established, H. pylori mainly resides in the gastric mucosa and interacts with the resident bacteria. How these interactions impact on H. pylori-caused diseases has been poorly studied in human. In this study, we analyzed the interactions between H. pylori and two bacteria, Streptococcus mitis and Lactobacillus fermentum that are present in the stomach of both healthy and gastric disease human patients. We have found that S. mitis produced and released one or more diffusible factors that induce growth inhibition and coccoid conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum secreted factors that promote survival of S. mitis during the stationary phase of growth. Using a metabolomics approach, we identified compounds that might be responsible for the conversion of H. pylori from spiral to coccoid cells. This study provide evidences that gastric bacteria influences H. pylori physiology and therefore possibly the diseases this bacterium causes.
  5. Chua EG, Wise MJ, Khosravi Y, Seow SW, Amoyo AA, Pettersson S, et al.
    DNA Res, 2017 Feb 01;24(1):37-49.
    PMID: 27803027 DOI: 10.1093/dnares/dsw046
    Helicobacter pylori is a highly successful gastric pathogen. High genomic plasticity allows its adaptation to changing host environments. Complete genomes of H. pylori clinical isolate UM032 and its mice-adapted serial derivatives 298 and 299, generated using both PacBio RS and Illumina MiSeq sequencing technologies, were compared to identify novel elements responsible for host-adaptation. The acquisition of a jhp0562-like allele, which encodes for a galactosyltransferase, was identified in the mice-adapted strains. Our analysis implies a new β-1,4-galactosyltransferase role for this enzyme, essential for Ley antigen expression. Intragenomic recombination between babA and babB genes was also observed. Further, we expanded on the list of candidate genes whose expression patterns have been mediated by upstream homopolymer-length alterations to facilitate host adaption. Importantly, greater than four-fold reduction of mRNA levels was demonstrated in five genes. Among the down-regulated genes, three encode for outer membrane proteins, including BabA, BabB and HopD. As expected, a substantial reduction in BabA protein abundance was detected in mice-adapted strains 298 and 299 via Western analysis. Our results suggest that the expression of Ley antigen and reduced outer membrane protein expressions may facilitate H. pylori colonisation of mouse gastric epithelium.
  6. Sidahmed HM, Hashim NM, Amir J, Abdulla MA, Hadi AH, Abdelwahab SI, et al.
    Phytomedicine, 2013 Jul 15;20(10):834-43.
    PMID: 23570997 DOI: 10.1016/j.phymed.2013.03.002
    Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (p<0.05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate. Moreover, PA significantly (p<0.05) reduced the elevated MDA level due to ethanol administration. The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori.
  7. Khosravi Y, Loke MF, Goh KL, Vadivelu J
    Front Microbiol, 2016;7:1462.
    PMID: 27695448
    Helicobacter pylori is the dominant species of the human gastric microbiota and is present in the stomach of more than half of the human population worldwide. Colonization by H. pylori causes persistent inflammatory response and H. pylori-induced gastritis is the strongest singular risk factor for the development of gastric adenocarcinoma. However, only a small proportion of infected individuals develop malignancy. Besides H. pylori, other microbial species have also been shown to be related to gastritis. We previously reported that interspecies microbial interaction between H. pylori and S. mitis resulted in alteration of their metabolite profiles. In this study, we followed up by analyzing the changing protein profiles of H. pylori and S. mitis by LC/Q-TOF mass spectrometry to understand the different response of the two bacterial species in a multi-species micro-environment. Differentially-expressed proteins in mono- and co-cultures could be mapped into 18 biological pathways. The number of proteins involve in RNA degradation, nucleotide excision repair, mismatch repair, and lipopolysaccharide (LPS) biosynthesis were increased in co-cultured H. pylori. On the other hand, fewer proteins involve in citrate cycle, glycolysis/ gluconeogenesis, aminoacyl-tRNA biosynthesis, translation, metabolism, and cell signaling were detected in co-cultured H. pylori. This is consistent with our previous observation that in the presence of S. mitis, H. pylori was transformed to coccoid. Interestingly, phosphoglycerate kinase (PGK), a major enzyme used in glycolysis, was found in abundance in co-cultured S. mitis and this may have enhanced the survival of S. mitis in the multi-species microenvironment. On the other hand, thioredoxin (TrxA) and other redox-regulating enzymes of H. pylori were less abundant in co-culture possibly suggesting reduced oxidative stress. Oxidative stress plays an important role in tissue damage and carcinogenesis. Using the in vitro co-culture model, this study emphasized the possibility that pathogen-microbiota interaction may have a protective effect against H. pylori-associated carcinogenesis.
  8. Yap TW, Chan WK, Leow AH, Azmi AN, Loke MF, Vadivelu J, et al.
    PLoS One, 2015;10(3):e0121908.
    PMID: 25799401 DOI: 10.1371/journal.pone.0121908
    BACKGROUND: Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible persons. The prevalence of CD in Malaysia is unknown. We aim to determine the seroprevalence of CD antibodies and also investigate the correlation between H. pylori infection and CD in the young and healthy multiracial Malaysian population.

    METHODS: Healthy young adult volunteers between the ages of 18-30 years were consecutively recruited from June 2012 to May 2014 at the University of Malaya Medical Centre (UMMC), Kuala Lumpur. Serum samples from all the participants were tested for anti-gliadin antibody immunoglobulin A/immunoglobulin G (IgA/IgG) and anti-tissue transglutaminase antibody (tTG) IgA/IgG. Samples positive for both anti-gliadin and anti-tTG were further validated for anti-human endomysial IgA antibodies (EmA). Serological diagnosis of CD was made when anti-gliadin, anti-tTG and anti-EmA were positive.

    RESULTS: 562 qualified participants with mean age 24 ± 2.4 years old were recruited into our study. CD was found in 7 participants where most of them were asymptomatic and unaware of their CD status. The median of anti-gliadin and anti-tTG IgA/IgG value was 38.2 U/ml (interquartile range, 28.3-60.4 U/ml) and 49.2 U/ml (interquartile range, 41.1-65.9 U/ml), respectively. Seroprevalence of CD antibodies was 1.9% (6 out of 324) in female while only 0.4% (1 out of 238) in male. Seroprevalence among Malay was 0.8% (2 of 236), Chinese was 1.7% (3 of 177) and Indian was 1.3% (2 of 149). Overall, seroprevalence of CD antibodies in healthy asymptomatic adults in the Malaysian population was 1.25% (95% CI, 0.78%-1.72%). No significant relationship was discovered between CD and H. pylori infection.

    CONCLUSIONS: The seroprevalence of CD antibodies in healthy young adults in the Malaysian population was 1.25% (1 in 100). CD is underdiagnosed and it could be a much greater problem in Malaysia than previously thought.

  9. 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.

  10. Ravishankar Ram M, Goh KL, Leow AH, Poh BH, Loke MF, Harrison R, et al.
    PLoS One, 2015;10(11):e0141865.
    PMID: 26559190 DOI: 10.1371/journal.pone.0141865
    Helicobacter pylori (H. pylori) -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs) and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs) associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD), 40 with peptic ulcer disease (PUD) and 15 with gastric cancer (GC) subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up-regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease.
  11. Rosli NA, Al-Maleki AR, Loke MF, Chua EG, Alhoot MA, Vadivelu J
    Gut Pathog, 2023 Oct 28;15(1):52.
    PMID: 37898785 DOI: 10.1186/s13099-023-00579-4
    BACKGROUND: Clarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori strains that have evolved antibiotic resistance can help create a more effective and individualised antibiotic treatment plan. However, little is understood about the genetic reprogramming linked to clarithromycin exposure and the emergence of antibiotic resistance in H. pylori. Therefore, this study aims to identify compensatory mutations and biofilm formation associated with the development of clarithromycin resistance in H. pylori. Clarithromycin-sensitive H. pylori clinical isolates were induced to develop clarithromycin resistance through in vitro exposure to incrementally increasing concentration of the antibiotic. The genomes of the origin sensitive isolates (S), isogenic breakpoint (B), and resistant isolates (R) were sequenced. Single nucleotide variations (SNVs), and insertions or deletions (InDels) associated with the development of clarithromycin resistance were identified. Growth and biofilm production were also assessed.

    RESULTS: The S isolates with A2143G mutation in the 23S rRNA gene were successfully induced to be resistant. According to the data, antibiotic exposure may alter the expression of certain genes, including those that code for the Cag4/Cag protein, the vacuolating cytotoxin domain-containing protein, the sel1 repeat family protein, and the rsmh gene, which may increase the risk of developing and enhances virulence in H. pylori. Enhanced biofilm formation was detected among R isolates compared to B and S isolates. Furthermore, high polymorphism was also detected among the genes associated with biofilm production.

    CONCLUSIONS: Therefore, this study suggests that H. pylori may acquire virulence factors while also developing antibiotic resistance due to clarithromycin exposure.

  12. Khosravi Y, Loke MF, Chua EG, Tay ST, Vadivelu J
    ScientificWorldJournal, 2012;2012:654939.
    PMID: 22792048 DOI: 10.1100/2012/654939
    Carbapenems are the primary choice of treatment for severe Pseudomonas aeruginosa infection. However, the emergence of carbapenem resistance due to the production of metallo-β-lactamases (MBLs) is of global concern. In this study, 90 imipenem- (IPM- or IP-) resistant P. aeruginosa (IRPA) isolates, including 32 previously tested positive and genotyped for MBL genes by PCR, were subjected to double-disk synergy test (DDST), combined disk test (CDT), and imipenem/imipenem-inhibitor (IP/IPI) E-test to evaluate their MBLs detection capability. All three methods were shown to have a sensitivity of 100%. However, DDST was the most specific of the three (96.6%), followed by IP/IPI E-test interpreted based on the single criteria of IP/IPI ≥8 as positive (62.1%), and CDT was the least specific (43.1%). Based on the data from this evaluation, we propose that only IRPA with IP MIC >16 μg/mL and IP/IPI ≥8 by IP/IPI E-test should be taken as positive for MBL activity. With the new dual interpretation criteria, the MBL IP/IPI E-test was shown to achieve 100% sensitivity as well as specificity for the IRPA in this study. Therefore, the IP/IPI E-test is a viable alternative phenotypic assay to detect MBL production in IRPA in our population in circumstances where PCR detection is not a feasible option.
  13. Péré-Védrenne C, Flahou B, Loke MF, Ménard A, Vadivelu J
    Helicobacter, 2017 Sep;22 Suppl 1.
    PMID: 28891140 DOI: 10.1111/hel.12407
    The current article is a review of the most important and relevant literature published in 2016 and early 2017 on non-Helicobacter pylori Helicobacter infections in humans and animals, as well as interactions between H. pylori and the microbiota of the stomach and other organs. Some putative new Helicobacter species were identified in sea otters, wild boars, dogs, and mice. Many cases of Helicobacter fennelliae and Helicobacter cinaedi infection have been reported in humans, mostly in immunocompromised patients. Mouse models have been used frequently as a model to investigate human Helicobacter infection, although some studies have investigated the pathogenesis of Helicobacters in their natural host, as was the case for Helicobacter suis infection in pigs. Our understanding of both the gastric and gut microbiome has made progress and, in addition, interactions between H. pylori and the microbiome were demonstrated to go beyond the stomach. Some new approaches of preventing Helicobacter infection or its related pathologies were investigated and, in this respect, the probiotic properties of Saccharomyces, Lactobacillus and Bifidobacterium spp. were confirmed.
  14. Leow AH, Azmi AN, Loke MF, Vadivelu J, Graham DY, Goh KL
    J Dig Dis, 2018 Nov;19(11):674-677.
    PMID: 30307122 DOI: 10.1111/1751-2980.12679
    OBJECTIVE: The 7-day standard triple therapy (STT) gives unacceptablly low eradication rates of Helicobacter pylori (H. pylori). We aimed to examine whether extending STT from 7 days to 14 days or adding a bismuth compound to a 7-day STT would result in better eradication rates.

    METHODS: H. pylori-positive patients were assigned to Group A (7-day STT; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily, for 7 days), Group B (7-day STT with bismuth; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily and bismuth subcitrate 240 mg twice daily, for 7 days) and Group C (14-day STT; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily for 14 days). Eradication was tested using 13 C-UBT at least 4 weeks after the completion of therapy.

    RESULTS: A total of 364 patients were recruited. In the intention-to-treat analysis, eradication rates were 79.3% (96/121; 95% confidence interval [CI] 71.3-85.6%) for 7-day STT, 81.7% (98/120; 95% CI 73.8-87.6%) for 7-day STT with bismuth, and 88.6% (109/123; 95% CI 81.8-93.1%) for 14-day STT, respectively. Statistical significance was achieved between the 7-day and the 14-day STT treatment (P = 0.048).

    CONCLUSIONS: Adding bismuth to the 7-day STT did not result in an increase in the eradication rate. Extending the STT to 14 days, however, achieved a significantly higher eradication rate. Nevertheless, this did not achieve the targeted 90% eradication rate on intention-to-treat analysis.

  15. Rehvathy V, Tan MH, Gunaletchumy SP, Teh X, Wang S, Baybayan P, et al.
    Genome Announc, 2013;1(5).
    PMID: 24051312 DOI: 10.1128/genomeA.00687-13
    Helicobacter pylori causes human gastroduodenal diseases, including chronic gastritis and peptic ulcer disease. It is also a major microbial risk factor for the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Twenty-one strains with different ethnicity, disease, and antimicrobial susceptibility backgrounds were sequenced by use of Illumina HiSeq and PacBio RS platforms.
  16. Chan KG, Loke MF, Ong BL, Wong YL, Hong KW, Tan KH, et al.
    PeerJ, 2015;3:e1367.
    PMID: 26587340 DOI: 10.7717/peerj.1367
    Background. Two non-tuberculous mycobacterial strains, UM_3 and UM_11, were isolated from the trunk wash of captive elephants in Malaysia. As they appeared to be identical phenotypes, they were investigated further by conventional and whole genome sequence-based methods of strain differentiation. Methods. Multiphasic investigations on the isolates included species identification with hsp65 PCR-sequencing, conventional biochemical tests, rapid biochemical profiling using API strips and the Biolog Phenotype Microarray analysis, protein profiling with liquid chromatography-mass spectrometry, repetitive sequence-based PCR typing and whole genome sequencing followed by phylogenomic analyses. Results. The isolates were shown to be possibly novel slow-growing schotochromogens with highly similar biological and genotypic characteristics. Both strains have a genome size of 5.2 Mbp, G+C content of 68.8%, one rRNA operon and 52 tRNAs each. They qualified for classification into the same species with their average nucleotide identity of 99.98% and tetranucleotide correlation coefficient of 0.99999. At the subspecies level, both strains showed 98.8% band similarity in the Diversilab automated repetitive sequence-based PCR typing system, 96.2% similarity in protein profiles obtained by liquid chromatography mass spectrometry, and a genomic distance that is close to zero in the phylogenomic tree constructed with conserved orthologs. Detailed epidemiological tracking revealed that the elephants shared a common habitat eight years apart, thus, strengthening the possibility of a clonal relationship between the two strains.
  17. Loke MF, Chua EG, Gan HM, Thulasi K, Wanyiri JW, Thevambiga I, et al.
    PLoS One, 2018;13(12):e0208584.
    PMID: 30576312 DOI: 10.1371/journal.pone.0208584
    Colorectal cancer (CRC) is ranked the third most common cancer in human worldwide. However, the exact mechanisms of CRC are not well established. Furthermore, there may be differences between mechanisms of CRC in the Asian and in the Western populations. In the present study, we utilized a liquid chromatography-mass spectrometry (LC-MS) metabolomic approach supported by the 16S rRNA next-generation sequencing to investigate the functional and taxonomical differences between paired tumor and unaffected (normal) surgical biopsy tissues from 17 Malaysian patients. Metabolomic differences associated with steroid biosynthesis, terpenoid biosynthesis and bile metabolism could be attributed to microbiome differences between normal and tumor sites. The relative abundances of Anaerotruncus, Intestinimonas and Oscillibacter displayed significant relationships with both steroid biosynthesis and terpenoid and triterpenoid biosynthesis pathways. Metabolites involved in serotonergic synapse/ tryptophan metabolism (Serotonin and 5-Hydroxy-3-indoleacetic acid [5-HIAA]) were only detected in normal tissue samples. On the other hand, S-Adenosyl-L-homocysteine (SAH), a metabolite involves in methionine metabolism and methylation, was frequently increased in tumor relative to normal tissues. In conclusion, this study suggests that local microbiome dysbiosis may contribute to functional changes at the cancer sites. Results from the current study also contributed to the list of metabolites that are found to differ between normal and tumor sites in CRC and supported our quest for understanding the mechanisms of carcinogenesis.
  18. Wong EHJ, Ng CG, Goh KL, Vadivelu J, Ho B, Loke MF
    Sci Rep, 2018 01 23;8(1):1409.
    PMID: 29362474 DOI: 10.1038/s41598-018-19697-0
    The biofilm-forming-capability of Helicobacter pylori has been suggested to be among factors influencing treatment outcome. However, H. pylori exhibit strain-to-strain differences in biofilm-forming-capability. Metabolomics enables the inference of spatial and temporal changes of metabolic activities during biofilm formation. Our study seeks to examine the differences in metabolome of low and high biofilm-formers using the metabolomic approach. Eight H. pylori clinical strains with different biofilm-forming-capability were chosen for metabolomic analysis. Bacterial metabolites were extracted using Bligh and Dyer method and analyzed by Liquid Chromatography/Quadrupole Time-of-Flight mass spectrometry. The data was processed and analyzed using the MassHunter Qualitative Analysis and the Mass Profiler Professional programs. Based on global metabolomic profiles, low and high biofilm-formers presented as two distinctly different groups. Interestingly, low-biofilm-formers produced more metabolites than high-biofilm-formers. Further analysis was performed to identify metabolites that differed significantly (p-value 
  19. Munusamy K, Loke MF, Vadivelu J, Tay ST
    Microb Pathog, 2021 Mar;152:104614.
    PMID: 33202254 DOI: 10.1016/j.micpath.2020.104614
    Candidiasis is the most common fungal infection associated with high morbidity and mortality among immunocompromised patients. The ability to form biofilm is essential for Candida albicans pathogenesis and drug resistance. In this study, the planktonic cell and biofilm proteomes of C. albicans SC5314 strain analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS) were compared. In total, 280 and 449 proteins are annotated from the planktonic cell and biofilm proteomes, respectively. The biofilm proteome demonstrated significantly higher proportion of proteins associated with the endomembrane system, mitochondrion and cytoplasm than planktonic proteome. Among proteins detected, 143 and 207 biological processes are annotated, of which, 38 and 102 are specific to the planktonic cell and biofilm proteomes, respectively, while 105 are common biological processes. The specific biological processes of C. albicans planktonic cell proteome are associated with cell polarity, energy metabolism and nucleotide (purine) metabolism, oxido-reduction coenzyme metabolic process, monosaccharide and amino acid (methionine) biosynthesis, regulation of anatomical structure morphogenesis and cell cycling, and single organism reproduction. Meanwhile, regulation of cellular macromolecule biosynthesis and metabolism, transcription and gene expression are major biological processes specifically associated with C. albicans biofilm proteome. Biosynthesis of leucine, isoleucine, and thiocysteine are highlighted as planktonic-related pathways, whereas folate metabolism, fatty acid metabolism and biosynthesis of amino acids (lysine, serine and glycine) are highlighted as biofilm-related pathways. In summary, LC-MS-based proteomic analysis reveals different adaptative strategies of C. albicans via specific biological and metabolic processes for planktonic cell and biofilm lifestyles. The mass spectrometry data are available via ProteomeXchange with identifiers PXD007830 (for biofilm proteome) and PXD007831 (for planktonic cell proteome).
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links