Displaying publications 61 - 80 of 120 in total

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  1. Ng CG, Loke MF, Goh KL, Vadivelu J, Ho B
    Food Microbiol, 2017 Apr;62:68-76.
    PMID: 27889168 DOI: 10.1016/j.fm.2016.10.010
    To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment.
  2. 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.

  3. Al-Maleki AR, Mariappan V, Vellasamy KM, Tay ST, Vadivelu J
    PLoS One, 2015;10(5):e0127398.
    PMID: 25996927 DOI: 10.1371/journal.pone.0127398
    Burkholderia pseudomallei primary diagnostic cultures demonstrate colony morphology variation associated with expression of virulence and adaptation proteins. This study aims to examine the ability of B. pseudomallei colony variants (wild type [WT] and small colony variant [SCV]) to survive and replicate intracellularly in A549 cells and to identify the alterations in the protein expression of these variants, post-exposure to the A549 cells. Intracellular survival and cytotoxicity assays were performed followed by proteomics analysis using two-dimensional gel electrophoresis. B. pseudomallei SCV survive longer than the WT. During post-exposure, among 259 and 260 protein spots of SCV and WT, respectively, 19 were differentially expressed. Among SCV post-exposure up-regulated proteins, glyceraldehyde 3-phosphate dehydrogenase, fructose-bisphosphate aldolase (CbbA) and betaine aldehyde dehydrogenase were associated with adhesion and virulence. Among the down-regulated proteins, enolase (Eno) is implicated in adhesion and virulence. Additionally, post-exposure expression profiles of both variants were compared with pre-exposure. In WT pre- vs post-exposure, 36 proteins were differentially expressed. Of the up-regulated proteins, translocator protein, Eno, nucleoside diphosphate kinase (Ndk), ferritin Dps-family DNA binding protein and peptidyl-prolyl cis-trans isomerase B were implicated in invasion and virulence. In SCV pre- vs post-exposure, 27 proteins were differentially expressed. Among the up-regulated proteins, flagellin, Eno, CbbA, Ndk and phenylacetate-coenzyme A ligase have similarly been implicated in adhesion, invasion. Protein profiles differences post-exposure provide insights into association between morphotypic and phenotypic characteristics of colony variants, strengthening the role of B. pseudomallei morphotypes in pathogenesis of melioidosis.
  4. Barathan M, Shivashekaregowda NKH, Hoong SM, Vellasamy KM, Vadivelu J
    Toxicol Appl Pharmacol, 2023 Dec 15;481:116767.
    PMID: 38007073 DOI: 10.1016/j.taap.2023.116767
    Current treatments for stomach cancer are often effective in curing cancer. However, these treatments can also have significant side effects, and they may not be effective in all cases. Hence synthetic compounds exhibit promise as potential agents for cancer treatment. In a previous study, we identified (E)-N'- (2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) as a novel antimycobacterial derivative of isoniazid with cytotoxic effects on the MCF-7 breast cancer cell line. This led us to investigate the potential anti-cancer properties of ITHB4 against adenocarcinoma gastric (AGS) cell line. The cytotoxic effect of ITHB4 has been determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and further confirmed for anticancer properties by means of apoptosis, reactive oxygen species (ROS), nuclear fragmentation, lactate dehydrogenase (LDH), caspases, cytokines and morphological including phenotypic changes of cells assay. The ITHB4 demonstrated a lower IC50 in inhibiting growth of AGS cells at 24 h compared to 48 and 72 h. ITHB4 has also shown no toxicity human immune cells. Treatment of ITHB4 against AGS for 24 h eventually lead to formation of early apoptotic AGS cells, reduced mitochondrial membrane potential, nuclear condensation, and nuclear fragmentation lastly increased in ROS levels together with the release of LDH, and secretion of caspases. The altered cytokine profile in ITHB4 treated AGS hints at the possibility that ITHB4 may possess anti-tumor and anti-inflammatory properties. Our results in this study demonstrate that ITHB4 has almost similar chemotherapeutic properties against gastric adenocarcinoma cells compared to breast cancer cell. This is suggesting that the anticancer capabilities of this compound should be in vivo and clinically assessed.
  5. Sim JH, Abdul Aziz YF, Mansor A, Vijayananthan A, Foong CC, Vadivelu J
    Med Educ Online, 2015;20:26185.
    PMID: 25697602 DOI: 10.3402/meo.v20.26185
    INTRODUCTION: The purpose of this study was to compare students' performance in the different clinical skills (CSs) assessed in the objective structured clinical examination.

    METHODS: Data for this study were obtained from final year medical students' exit examination (n=185). Retrospective analysis of data was conducted using SPSS. Means for the six CSs assessed across the 16 stations were computed and compared.

    RESULTS: Means for history taking, physical examination, communication skills, clinical reasoning skills (CRSs), procedural skills (PSs), and professionalism were 6.25±1.29, 6.39±1.36, 6.34±0.98, 5.86±0.99, 6.59±1.08, and 6.28±1.02, respectively. Repeated measures ANOVA showed there was a significant difference in the means of the six CSs assessed [F(2.980, 548.332)=20.253, p<0.001]. Pairwise multiple comparisons revealed significant differences between the means of the eight pairs of CSs assessed, at p<0.05.

    CONCLUSIONS: CRSs appeared to be the weakest while PSs were the strongest, among the six CSs assessed. Students' unsatisfactory performance in CRS needs to be addressed as CRS is one of the core competencies in medical education and a critical skill to be acquired by medical students before entering the workplace. Despite its challenges, students must learn the skills of clinical reasoning, while clinical teachers should facilitate the clinical reasoning process and guide students' clinical reasoning development.

  6. Foong CC, Bashir Ghouse NL, Lye AJ, Pallath V, Hong WH, Vadivelu J
    Ann Med, 2022 Dec;54(1):195-210.
    PMID: 35019800 DOI: 10.1080/07853890.2021.1967440
    BACKGROUND: Poor academic performance and failure can cause undesired effects for students, schools, and society. Understanding why some students fail while their peers succeed is important to enhance student performance. Therefore, this study explores the differences in the learning process between high- and low-achieving pre-clinical medical students from a theory of action perspective.

    METHODS: This study employed a qualitative instrumental case study design intended to compare two groups of students-high-achieving students (n = 14) and low-achieving students (n = 5), enrolled in pre-clinical medical studies at the Universiti Malaya, Malaysia. Data were collected through reflective journals and semi-structured interviews. Regarding journaling, participants were required to recall their learning experiences of the previous academic year. Two analysts coded the data and then compared the codes of high- and low-achieving students. The third analyst reviewed the codes. Themes were identified iteratively, working towards comparing the learning processes of high- and low-achieving students.

    RESULTS: Data analysis revealed four themes-motivation and expectation, study methods, self-management, and flexibility of mindset. First, high-achieving students were more motivated and had higher academic expectations than low-achieving students. Second, high-achieving students adopted study planning and deep learning approaches, whereas low-achieving students adopted superficial learning approaches. Third, in contrast to low-achieving students, high-achieving students exhibited better time management and studied consistently. Finally, high-achieving students proactively sought external support and made changes to overcome challenges. In contrast, low-achieving students were less resilient and tended to avoid challenges.

    CONCLUSION: Based on the theory of action, high-achieving students utilize positive governing variables, whereas low-achieving students are driven by negative governing variables. Hence, governing variable-based remediation is needed to help low-achieving students interrogate the motives behind their actions and realign positive governing variables, actions, and intended outcomes.Key MessagesThis study found four themes describing the differences between high- and low-achieving pre-clinical medical students: motivation and expectation, study methods, self-management, and flexibility of mindset.Based on the theory of action approach, high-achieving pre-clinical medical students are fundamentally different from their low-achieving peers in terms of their governing variables, with the positive governing variables likely to have guided them to act in a manner beneficial to and facilitating desirable academic performance.Governing variable-based remediation may help students interrogate the motives of their actions.

  7. Appanna R, Huat TL, See LL, Tan PL, Vadivelu J, Devi S
    Clin Vaccine Immunol, 2007 Aug;14(8):969-77.
    PMID: 17567768
    Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas in the world. Attempts to develop effective vaccines have been hampered by the lack of understanding of the pathogenesis of the disease and the absence of suitable experimental models for dengue viral infection. The magnitude of T-cell responses has been reported to correlate with dengue disease severity. Sixty Malaysian adults with dengue viral infections were investigated for their dengue virus-specific T-cell responses to 32 peptides antigens from the structural and nonstructural regions from a dengue virus isolate. Seventeen different peptides from the C, E, NS2B, NS3, NS4A, NS4B, and NS5 regions were found to evoke significant responses in a gamma interferon enzyme-linked immunospot (ELISPOT) assay of samples from 13 selected patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). NS3 and predominantly NS3(422-431) were found to be important T-cell targets. The highest peaks of T-cell responses observed were in responses to NS3(422-431) and NS5(563-571) in DHF patients. We also found almost a sevenfold increase in T-cell response in three DHF patients compared to three DF patient responses to peptide NS3(422-431). A large number of patients' T cells also responded to the NS2B(97-106) region. The ELISPOT analyses also revealed high frequencies of T cells that recognize both serotype-specific and cross-reactive dengue virus antigens in patients with DHF.
  8. Gunaletchumy SP, Seevasant I, Tan MH, Croft LJ, Mitchell HM, Goh KL, et al.
    Sci Rep, 2014 Dec 11;4:7431.
    PMID: 25503415 DOI: 10.1038/srep07431
    Helicobacter pylori infection results in diverse clinical conditions ranging from chronic gastritis and ulceration to gastric adenocarcinoma. Among the multiethnic population of Malaysia, Indians consistently have a higher H. pylori prevalence as compared with Chinese and Malays. Despite the high prevalence of H. pylori, Indians have a relatively low incidence of peptic ulcer disease and gastric cancer. In contrast, gastric cancer and peptic ulcer disease incidence is high in Chinese. H. pylori strains from Chinese strains predominantly belong to the hspEAsia subpopulation while Indian/Malay strains mainly belong to the hspIndia subpopulation. By comparing the genome of 27 Asian strains from different subpopulations, we identified six genes associated with risk of H. pylori-induced peptic ulcer disease and gastric cancer. This study serves as an important foundation for future studies aiming to understand the role of bacterial factors in H. pylori-induced gastro-duodenal diseases.
  9. 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.
  10. Zulkefli NJ, Mariappan V, Vellasamy KM, Chong CW, Thong KL, Ponnampalavanar S, et al.
    PeerJ, 2016;4:e1802.
    PMID: 26998408 DOI: 10.7717/peerj.1802
    Background. Central intermediary metabolism (CIM) in bacteria is defined as a set of metabolic biochemical reactions within a cell, which is essential for the cell to survive in response to environmental perturbations. The genes associated with CIM are commonly found in both pathogenic and non-pathogenic strains. As these genes are involved in vital metabolic processes of bacteria, we explored the efficiency of the genes in genotypic characterization of Burkholderia pseudomallei isolates, compared with the established pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) schemes. Methods. Nine previously sequenced B. pseudomallei isolates from Malaysia were characterized by PFGE, MLST and CIM genes. The isolates were later compared to the other 39 B. pseudomallei strains, retrieved from GenBank using both MLST and sequence analysis of CIM genes. UniFrac and hierachical clustering analyses were performed using the results generated by both MLST and sequence analysis of CIM genes. Results. Genetic relatedness of nine Malaysian B. pseudomallei isolates and the other 39 strains was investigated. The nine Malaysian isolates were subtyped into six PFGE profiles, four MLST profiles and five sequence types based on CIM genes alignment. All methods demonstrated the clonality of OB and CB as well as CMS and THE. However, PFGE showed less than 70% similarity between a pair of morphology variants, OS and OB. In contrast, OS was identical to the soil isolate, MARAN. To have a better understanding of the genetic diversity of B. pseudomallei worldwide, we further aligned the sequences of genes used in MLST and genes associated with CIM for the nine Malaysian isolates and 39 B. pseudomallei strains from NCBI database. Overall, based on the CIM genes, the strains were subtyped into 33 profiles where majority of the strains from Asian countries were clustered together. On the other hand, MLST resolved the isolates into 31 profiles which formed three clusters. Hierarchical clustering using UniFrac distance suggested that the isolates from Australia were genetically distinct from the Asian isolates. Nevertheless, statistical significant differences were detected between isolates from Malaysia, Thailand and Australia. Discussion. Overall, PFGE showed higher discriminative power in clustering the nine Malaysian B. pseudomallei isolates and indicated its suitability for localized epidemiological study. Compared to MLST, CIM genes showed higher resolution in distinguishing those non-related strains and better clustering of strains from different geographical regions. A closer genetic relatedness of Malaysian isolates with all Asian strains in comparison to Australian strains was observed. This finding was supported by UniFrac analysis which resulted in geographical segregation between Australia and the Asian countries.
  11. Dieye Y, Mbengue B, Dagamajalu S, Fall MM, Loke MF, Nguer CM, et al.
    PeerJ, 2016;4:e1965.
    PMID: 27168977 DOI: 10.7717/peerj.1965
    Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoan Plasmodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasmodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death. Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines. Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.
  12. Suwarnalata G, Tan AH, Isa H, Gudimella R, Anwar A, Loke MF, et al.
    PLoS One, 2016;11(4):e0153725.
    PMID: 27100827 DOI: 10.1371/journal.pone.0153725
    Parkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case) and 30 age- and gender-matched H. pylori-seronegative PD patients (control) in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA), Platelet-derived growth factor B (PDGFB) and Eukaryotic translation initiation factor 4A3 (eIFA3). The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity.
  13. 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.

  14. Menon N, Mariappan V, Vellasamy KM, Samudi C, See JX, Ganesh PS, et al.
    Access Microbiol, 2020;2(5):acmi000110.
    PMID: 32974575 DOI: 10.1099/acmi.0.000110
    Burkholderia pseudomallei is the causative agent for melioidosis. Because of its intracellular nature, the bacterium is capable of replicating within a plethora of eukaryotic cell lines. B. pseudomallei can remain dormant within host cells without symptoms for years, causing recrudescent infections. Here, we investigated the pathogenesis mechanism behind the suppression of T cell responses by B. pseudomallei . Peripheral blood mononuclear cells (1×106 cells/well) isolated by Ficoll Paque (Sigma-Aldrich) density gradient centrifugation were incubated with optimized concentrations of bacterial crude culture filtrate antigens (CFAs) (10 ug ml-1) and heat-killed bacteria [1 : 10 multiplicity of infection (m.o.i.)]. Following incubation, cells were investigated for surface expression of coinhibitory molecules by flow cytometry. We found that B. pseudomallei induced the upregulation of programmed death 1 (PD-1), a molecule responsible for T cell exhaustion, on T cells in vitro following exposure to crude CFAs of B. pseudomallei . This upregulation of PD-1 probably contributes to poor immune surveillance and disease pathogenesis.
  15. Venkatramanan M, Sankar Ganesh P, Senthil R, Akshay J, Veera Ravi A, Langeswaran K, et al.
    ACS Omega, 2020 Oct 13;5(40):25605-25616.
    PMID: 33073086 DOI: 10.1021/acsomega.0c02483
    Chromobacterium violaceum (C. violaceum) is a Gram-negative, rod-shaped facultatively anaerobic bacterium implicated with recalcitrant human infections. Here, we evaluated the anti-QS and antibiofilm activities of ethyl acetate extracts of Passiflora edulis (P. edulis) on the likely inactivation of acyl-homoserine lactone (AHL)-regulated molecules in C. violaceum both by in vitro and in silico analyses. Our investigations showed that the sub-MIC levels were 2, 1, and 0.5 mg/mL, and the concentrations showed a marked reduction in violacein pigment production by 75.8, 64.6, and 35.2%. AHL quantification showed 72.5, 52.2, and 35.9% inhibitions, inhibitions of EPS production (72.8, 36.5, and 25.9%), and reductions in biofilm formation (90.7, 69.4, and 51.8%) as compared to a control. Light microscopy and CLSM analysis revealed dramatic reduction in the treated biofilm group as compared to the control. GC-MS analysis showed 20 major peaks whose chemical structures were docked as the CviR ligand. The highest docking score was observed for hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester bonds in the active site of CviR with a binding energy of -8.825 kcal/mol. Together, we found that hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester remarkably interacted with CviR to inhibit the QS system. Hence, we concluded that hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester of P. edulis could likely be evaluated for treating C. violaceum infections.
  16. 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.
  17. Yap TW, Leow AH, Azmi AN, Callahan DL, Perez-Perez GI, Loke MF, et al.
    Front Microbiol, 2017;8:536.
    PMID: 28424674 DOI: 10.3389/fmicb.2017.00536
    Background:Helicobacter pylori colonizes the gastric mucosa of more than half of the world's population. There is increasing evidence H. pylori protects against the development of obesity and childhood asthma/allergies in which the development of these diseases coincide with transient dysbiosis. However, the mechanism underlying the association of H. pylori eradication with human metabolic and immunological disorders is not well-established. In this study, we aimed to investigate the local and systemic effects of H. pylori eradication through untargeted fecal lipidomics and plasma metabolomics approaches by liquid chromatography mass spectrometry (LC-MS). Results: Our study revealed that eradication of H. pylori eradication (i.e., loss of H. pylori and/or H. pylori eradication therapy) changed many global metabolite/lipid features, with the majority being down-regulated. Our findings primarily show that H. pylori eradication affects the host energy and lipid metabolism which may eventually lead to the development of metabolic disorders. Conclusion: These predictive metabolic signatures of metabolic and immunological disorders following H. pylori eradication can provide insights into dynamic local and systemic metabolism related to H. pylori eradication in modulating human health.
  18. Vadivelu J, Vellasamy KM, Thimma J, Mariappan V, Kang WT, Choh LC, et al.
    PLoS Negl Trop Dis, 2017 01;11(1):e0005241.
    PMID: 28045926 DOI: 10.1371/journal.pntd.0005241
    BACKGROUND: During infection, successful bacterial clearance is achieved via the host immune system acting in conjunction with appropriate antibiotic therapy. However, it still remains a tip of the iceberg as to where persistent pathogens namely, Burkholderia pseudomallei (B. pseudomallei) reside/hide to escape from host immune sensors and antimicrobial pressure.

    METHODS: We used transmission electron microscopy (TEM) to investigate post-mortem tissue sections of patients with clinical melioidosis to identify the localisation of a recently identified gut microbiome, B. pseudomallei within host cells. The intranuclear presence of B. pseudomallei was confirmed using transmission electron microscopy (TEM) of experimentally infected guinea pig spleen tissues and Live Z-stack, and ImageJ analysis of fluorescence microscopy analysis of in vitro infection of A549 human lung epithelial cells.

    RESULTS: TEM investigations revealed intranuclear localization of B. pseudomallei in cells of infected human lung and guinea pig spleen tissues. We also found that B. pseudomallei induced actin polymerization following infection of A549 human lung epithelial cells. Infected A549 lung epithelial cells using 3D-Laser scanning confocal microscopy (LSCM) and immunofluorescence microscopy confirmed the intranuclear localization of B. pseudomallei.

    CONCLUSION: B. pseudomallei was found within the nuclear compartment of host cells. The nucleus may play a role as an occult or transient niche for persistence of intracellular pathogens, potentially leading to recurrrent episodes or recrudescence of infection.

  19. Yong YK, Tan HY, Saeidi A, Rosmawati M, Atiya N, Ansari AW, et al.
    Innate Immun, 2017 07;23(5):459-467.
    PMID: 28606013 DOI: 10.1177/1753425917714854
    Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2+CD4+T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA+ and nine were HBV DNA-. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69+ cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2+CD4+T cells, and the levels of cytokine expression correlated with functional cytokine levels.
  20. Barathan M, Riazalhosseini B, Iyadorai T, Vellasamy KM, Vadivelu J, Chang LY, et al.
    Microb Pathog, 2021 Dec;161(Pt A):105231.
    PMID: 34619310 DOI: 10.1016/j.micpath.2021.105231
    The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-α and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-α correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.
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