Displaying publications 41 - 60 of 120 in total

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  1. See JX, Samudi C, Saeidi A, Menon N, Choh LC, Vadivelu J, et al.
    PLoS Negl Trop Dis, 2016 Mar;10(3):e0004503.
    PMID: 26974441 DOI: 10.1371/journal.pntd.0004503
    Burkholderia pseudomallei (B. pseudomallei), the causative agent of melioidosis, is a deadly pathogen endemic across parts of tropical South East Asia and Northern Australia. B. pseudomallei can remain latent within the intracellular compartment of the host cell over prolonged periods of time, and cause persistent disease leading to treatment difficulties. Understanding the immunological mechanisms behind persistent infection can result in improved treatment strategies in clinical melioidosis.
  2. Khosravi Y, Loke MF, Chua EG, Tay ST, Vadivelu J
    ScientificWorldJournal, 2016;2016:9562039.
    PMID: 27314061
    [This corrects the article DOI: 10.1100/2012/654939.].
  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. Sidahmed HMA, Vadivelu J, Loke MF, Arbab IA, Abdul B, Sukari MA, et al.
    Phytomedicine, 2019 Mar 01;55:31-39.
    PMID: 30668441 DOI: 10.1016/j.phymed.2018.06.036
    BACKGROUND: Clausena excavata Burm.f. (Rutaceae) has been used for the treatment of stomach disorders including peptic ulcer.

    PURPOSE: In this study, we aimed to investigate dentatin isolated from C. excavata Burm.f., for anti-ulcer activity against ethanol ulcer model in rats.

    METHODS: Gastric acid output, ulcer index, serum profile, histological evaluation using Hematoxylin and eosin (HE), periodic acid Schiff base stainings and immunohistochemical localization for heat shock proteins 70 (HSP70) were all investigated. Possible involvement of reduced glutathione (GSH), lipid peroxidation, prostaglandin E2 (PGE2), superoxide dismutase (SOD) enzymes, radical scavenging, and anti-Helicobacter pylori activity were investigated.

    RESULTS: Dentatin showed anti-secretory activity against the pylorus ligature model and protected the gastric mucosa from ethanol ulceration, as revealed by the improved macroscopic and histological appearance. Dentatin significantly increased the gastric homogenate content of PGE2 GSH and SOD. Dentatin inhibited the lipid peroxidation as revealed by the reduced gastric content of malondialdehyde (MDA). Moreover, dentatin up-regulated HSP70 expression. However, dentatin showed insignificant anti-H. pylori activity.

    CONCLUSION: Dentatin possesses gastro-protective activity, which could be attributed to the anti-secretory, mucus production, anti-oxidant, and HSP70 activities.

  5. Al-Maleki AR, Vellasamy KM, Mariappan V, Venkatraman G, Tay ST, Vadivelu J
    Genomics, 2020 01;112(1):501-512.
    PMID: 30980902 DOI: 10.1016/j.ygeno.2019.04.002
    Differences in expression of potential virulence and survival genes were associated with B. pseudomallei colony morphology variants. Microarray was used to investigate B. pseudomallei transcriptome alterations among the wild type and small colony variant (SCV) pre- and post-exposed to A549 cells. SCV pre- and post-exposed have lower metabolic requirements and consume lesser energy than the wild type pre- and post-exposed to A549. However, both the wild type and SCV limit their metabolic activities post- infection of A549 cells and this is indicated by the down-regulation of genes implicated in the metabolism of amino acids, carbohydrate, lipid, and other amino acids. Many well-known virulence and survival factors, including T3SS, fimbriae, capsular polysaccharides and stress response were up-regulated in both the wild type and SCV pre- and post-exposed to A549 cells. Microarray analysis demonstrated essential differences in bacterial response associated with virulence and survival pre- and post-exposed to A549 cells.
  6. Muthusami S, Vidya B, Shankar EM, Vadivelu J, Ramachandran I, Stanley JA, et al.
    Curr Protein Pept Sci, 2020;21(1):52-65.
    PMID: 31702489 DOI: 10.2174/1389203720666191106113435
    Hormones are known to influence various body systems that include skeletal, cardiac, digestive, excretory, and immune systems. Emerging investigations suggest the key role played by secretions of endocrine glands in immune cell differentiation, proliferation, activation, and memory attributes of the immune system. The link between steroid hormones such as glucocorticoids and inflammation is widely known. However, the role of peptide hormones and amino acid derivatives such as growth and thyroid hormones, prolactin, dopamine, and thymopoietin in regulating the functioning of the immune system remains unclear. Here, we reviewed the findings pertinent to the functional role of hormone-immune interactions in health and disease and proposed perspective directions for translational research in the field.
  7. Barathan M, Zulpa AK, Vellasamy KM, Mariappan V, Shivashekaregowda NKH, Ibrahim ZA, et al.
    In Vivo, 2021 8 20;35(5):2675-2685.
    PMID: 34410956 DOI: 10.21873/invivo.12551
    BACKGROUND/AIM: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells.

    MATERIALS AND METHODS: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays.

    RESULTS: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G2/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death.

    CONCLUSION: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.

  8. Lee SS, Samarasekera DD, Sim JH, Hong WH, Foong CC, Pallath V, et al.
    Med Sci Educ, 2020 Mar;30(1):271-280.
    PMID: 34457667 DOI: 10.1007/s40670-019-00894-z
    Purpose: Research has shown that many undergraduate students struggle with self-regulated learning (SRL) in clinical year as they are insufficiently supported by the staff in the early year to prepare them for the transition. Hence, this study aims to find out the SRL strategies and the approaches that could promote SRL among pre-clinical students in two medical schools.

    Method: This is a mixed-method study. The Motivated Strategies for Learning Questionnaire (MSLQ) was used to collect student SRL strategies while semi-structured interviews with faculty members and focus group discussions with students were used to gather data on the approaches that promote SRL. Student MSLQ was analysed using descriptive statistics while interviews were transcribed verbatim and thematically analysed.

    Results: A pilot using MSLQ with 413 students recorded a Cronbach's alpha of 0.928 for the questionnaire. The actual study involved 457 Years 1 & 2 students. Students from both institutions are motivated by the Task Value, and they use Elaboration and Organisation strategies the most in their pre-clinical year. Three themes emerged from the qualitative analysis of this study: characteristics of strategies that promote SRL, hindrance in promoting SRL, and opportunities in promoting SRL.

    Conclusions: Our findings indicate that students' intrinsic motivation is generally high in pre-clinical year. However, metacognition and critical thinking strategies will need to be enhanced among students. Despite knowing teaching and learning approaches could promote these strategies, many teachers are still not confident in doing so and hence training dang sharing best practices might be helpful in promoting SRL.

  9. Mariappan V, Vellasamy KM, Barathan M, Girija ASS, Shankar EM, Vadivelu J
    Front Immunol, 2021;12:718719.
    PMID: 34456925 DOI: 10.3389/fimmu.2021.718719
    Burkholderia pseudomallei (B. pseudomallei) causes melioidosis, a potentially fatal disease for which no licensed vaccine is available thus far. The host-pathogen interactions in B. pseudomallei infection largely remain the tip of the iceberg. The pathological manifestations are protean ranging from acute to chronic involving one or more visceral organs leading to septic shock, especially in individuals with underlying conditions similar to COVID-19. Pathogenesis is attributed to the intracellular ability of the bacterium to 'step into' the host cell's cytoplasm from the endocytotic vacuole, where it appears to polymerize actin filaments to spread across cells in the closer vicinity. B. pseudomallei effectively evades the host's surveillance armory to remain latent for prolonged duration also causing relapses despite antimicrobial therapy. Therefore, eradication of intracellular B. pseudomallei is highly dependent on robust cellular immune responses. However, it remains ambiguous why certain individuals in endemic areas experience asymptomatic seroconversion, whereas others succumb to sepsis-associated sequelae. Here, we propose key insights on how the host's surveillance radars get commandeered by B. pseudomallei.
  10. Guang-Han O, Leang-Chung C, Vellasamy KM, Mariappan V, Li-Yen C, Vadivelu J
    PLoS One, 2016;11(7):e0158213.
    PMID: 27387381 DOI: 10.1371/journal.pone.0158213
    Burkholderia pseudomallei is an intracellular Gram-negative bacterial pathogen intrinsically resistant to a variety of antibiotics. Phages have been developed for use as an alternative treatment therapy, particularly for bacterial infections that do not respond to conventional antibiotics. In this study, we investigated the use of phages to treat cells infected with B. pseudomallei. Phage C34 isolated from seawater was purified and characterised on the basis of its host range and morphology using transmission electron microscopy (TEM). Phage C34 was able to lyse 39.5% of B. pseudomallei clinical strains. Due to the presence of contractile tail, phage C34 is classified as a member of the family Myoviridae, a tailed double-stranded DNA virus. When 2 × 105 A549 cells were exposed to 2 × 107 PFU of phage C34, 24 hours prior to infection with 2 × 106 CFU of B. pseudomallei, it was found that the survivability of the cells increased to 41.6 ± 6.8% as compared to 22.8 ± 6.0% in untreated control. Additionally, application of phage successfully rescued 33.3% of mice infected with B. pseudomallei and significantly reduced the bacterial load in the spleen of the phage-treated mice. These findings indicate that phage can be a potential antimicrobial agent for B. pseudomallei infections.
  11. 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.

  12. Mariappan V, Thavagnanam S, Vellasamy KM, Teh CJS, Atiya N, Ponnampalavanar S, et al.
    BMC Infect Dis, 2018 Sep 05;18(1):455.
    PMID: 30185168 DOI: 10.1186/s12879-018-3371-7
    BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis, which is a potentially life threatening disease endemic in Southeast Asian countries. In Malaysia, cystic fibrosis (CF) is an uncommon condition. The association between CF and B.pseudomallei infections has been reported previously. However, this is the first case report of a pediatric melioidosis relapse and co-infection with other Gram-negative bacteria in Malaysia.

    CASE PRESENTATION: A 14-year-old Chinese Malaysian boy presented with a history of recurrent pneumonia, poor growth and steatorrhoea since childhood, and was diagnosed with CF. B. pseudomallei was cultured from his sputum during three different admissions between 2013 and 2016. However, the patient succumbed to end stage of respiratory failure in 2017 despite antibiotics treatment against B.pseudomallei. The isolates were compared using multilocus-sequence typing and repetitive-element polymerase chain reaction (PCR), and confirmed that two of the isolates were of same sequence type, which may indicate relapse.

    CONCLUSIONS: CF patients should be aware of melioidosis in endemic regions, as it is an emerging infectious disease, especially when persistent or recurrent respiratory symptoms and signs of infection occur. The high prevalence rates of melioidosis in Malaysia warrants better management options to improve quality of life, and life expectancy in patients with CF. Travel activities to endemic regions should also be given more consideration, as this would be crucial to identify and initiate appropriate empiric treatment.

  13. Ganesh PS, Vishnupriya S, Vadivelu J, Mariappan V, Vellasamy KM, Shankar EM
    Microbiol. Immunol., 2020 Feb;64(2):87-98.
    PMID: 31769530 DOI: 10.1111/1348-0421.12762
    Burkholderia cepacia complex (Bcc) are opportunistic pathogens implicated with nosocomial infections, and high rates of morbidity and mortality, especially in individuals with cystic fibrosis (CF). B. cepacia are naturally resistant to different classes of antibiotics, and can subvert the host innate immune responses by producing quorum sensing (QS) controlled virulence factors and biofilms. It still remains a conundrum as to how exactly the bacterium survives the intracellular environment within the host cells of CF patients and immunocompromised individuals although the bacterium can invade human lung epithelial cells, neutrophils, and murine macrophages. The mechanisms associated with intracellular survival in the airway epithelial cells and the role of QS and virulence factors in B. cepacia infections in cystic fibrosis remain largely unclear. The current review focuses on understanding the role of QS-controlled virulence factors and biofilms, and provides additional impetus to understanding the potentials of QS-inhibitory strategies against B. cepacia.
  14. Iyadorai T, Mariappan V, Vellasamy KM, Wanyiri JW, Roslani AC, Lee GK, et al.
    PLoS One, 2020;15(1):e0228217.
    PMID: 31990962 DOI: 10.1371/journal.pone.0228217
    Escherichia coli (E. coli) from the B2 phylogenetic group is implicated in colorectal cancer (CRC) as it possesses a genomic island, termed polyketide synthetase (pks), which codes for the synthesis of colibactin, a genotoxin that induces DNA damage, cell cycle arrest, mutations and chromosomal instability in eukaryotic cells. The aim of this study was to detect and compare the prevalence of E. coli expressing pks (pks+ E. coli) in CRC patients and healthy controls followed by investigating the virulence triggered by pks+ E. coli using an in-vitro model. Mucosal colon tissues were collected and processed to determine the presence of pks+ E. coli. Thereafter, primary colon epithelial (PCE) and colorectal carcinoma (HCT116) cell lines were used to detect cytopathic response to the isolated pks+ E. coli strains. Our results showed 16.7% and 4.3% of CRC and healthy controls, respectively were pks+ E. coli. Further, PCE displayed syncytia and cell swelling and HCT116 cells, megalocytosis, in response to treatment with the isolated pks+ E. coli strains. In conclusion, pks+ E. coli was more often isolated from tissue of CRC patients compared to healthy individuals, and our in-vitro assays suggest these isolated strains may be involved in the initiation and development of CRC.
  15. Sim JH, Foong CC, Pallath V, Hong WH, Vadivelu J
    Int J Med Educ, 2021 May 27;12:86-93.
    PMID: 34049286 DOI: 10.5116/ijme.6082.7c41
    Objectives: This study aimed to validate a Malaysian version of a revised learning space questionnaire, as well as to test the utility of the revised questionnaire as a tool to investigate learning space preferences in a Malaysian medical school.

    Methods:   This is a cross-sectional survey. A convenient sample of 310 preclinical students of a public medical school in Malaysia were invited to participate. Validation data were collected using a revised 40-item, 5-point Likert scale learning space questionnaire.  The questionnaires were administered online via a student e-learning platform.  Data analysis was conducted using IBM SPSS version 24.  Exploratory factor analysis was conducted to examine the factor structure of the revised questionnaire to provide evidence for construct validity.  To assess the internal consistency of the revised questionnaire, Cronbach's alpha coefficients (α) were computed across all the items as well as for items within each of the factor.

    Results: A total of 223 (71.94%) preclinical students completed and returned the questionnaire. In the final analysis, exploratory factor analysis with principal axis factoring and an oblimin rotation identified a six-factor, 20-item factor solution. Reliability analysis reported good internal consistency for the revised questionnaire, with an overall Cronbach's alpha of 0.845, and Cronbach's alpha ranging from 0.800 to 0.925 for the six factors.

    Conclusions:   This study established evidence for the construct validity and internal consistency of the revised questionnaire.  The revised questionnaire appears to have utility as an instrument to investigate learning space preferences in Malaysian medical schools.

  16. Cheah CW, Al-Maleki AR, Vadivelu J, Danaee M, Sockalingam S, Baharuddin NA, et al.
    Int J Rheum Dis, 2020 Oct;23(10):1344-1352.
    PMID: 32743970 DOI: 10.1111/1756-185X.13919
    INTRODUCTION: Rheumatoid arthritis (RA) is associated with chronic periodontitis (CP) due to shared risk factors, immuno-genetics and tissue destruction pathways. Human cathelicidin LL-37 has been suggested as a possible mechanistic link for these diseases. This study investigated the levels of salivary and serum LL-37 in subjects with RA and CP and their correlation with disease parameters.

    METHOD: Subjects were allocated into RA (n = 49) or non-RA (NRA) (n = 55) groups, where 3 subgroups were further established; chronic periodontitis (CP), gingivitis (G) and periodontal health (H). Demographic and periodontal parameters were collected. Rheumatology data were obtained from hospital records. Serum and salivary LL-37 levels were measured using enzyme-linked immunosorbent assay and compared for all groups.

    RESULTS: For salivary LL-37, RA-CP was significantly higher than NRA-G and NRA-H (P = .047). For serum LL-37, all RA and NRA-CP were significantly higher than NRA-G and NRA-H (P = .024). Salivary LL-37 correlated negatively with clinical attachment loss (CAL) (P = .048), but positively with erythrocyte sedimentation rate (ESR) in RA-H (P = .045). Serum LL-37 showed positive correlation with ESR (P = .037) in RA-G, with C-reactive protein (P = .017) in RA-H, but negative correlation with number of teeth (P = .002) in NRA-CP. Rheumatology data correlated positively with periodontal parameters in RA-CP group.

    CONCLUSION: NRA-CP subjects with high serum LL-37 should receive comprehensive periodontal therapy. Positive correlation between rheumatology data and periodontal parameters showed that RA disease stability may be obtained by assessing the periodontal condition. Periodontal therapy is necessary to compliment RA treatment to achieve optimum outcome for RA patients with concurrent CP.

  17. Cheok YY, Lee CYQ, Cheong HC, Vadivelu J, Looi CY, Abdullah S, et al.
    Microorganisms, 2021 Dec 03;9(12).
    PMID: 34946105 DOI: 10.3390/microorganisms9122502
    Helicobacter pylori is well established as a causative agent for gastritis, peptic ulcer, and gastric cancer. Armed with various inimitable virulence factors, this Gram-negative bacterium is one of few microorganisms that is capable of circumventing the harsh environment of the stomach. The unique spiral structure, flagella, and outer membrane proteins accelerate H. pylori movement within the viscous gastric mucosal layers while facilitating its attachment to the epithelial cells. Furthermore, secretion of urease from H. pylori eases the acidic pH within the stomach, thus creating a niche for bacteria survival and replication. Upon gaining a foothold in the gastric epithelial lining, bacterial protein CagA is injected into host cells through a type IV secretion system (T4SS), which together with VacA, damage the gastric epithelial cells. H. pylori does not only establishes colonization in the stomach, but also manipulates the host immune system to permit long-term persistence. Prolonged H. pylori infection causes chronic inflammation that precedes gastric cancer. The current review provides a brief outlook on H. pylori survival tactics, bacterial-host interaction and their importance in therapeutic intervention as well as vaccine development.
  18. See JX, Chandramathi S, Abdulla MA, Vadivelu J, Shankar EM
    PLoS Negl Trop Dis, 2017 Aug;11(8):e0005702.
    PMID: 28820897 DOI: 10.1371/journal.pntd.0005702
    BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes. Moreover, recurrence rates in melioidosis patients can be up to ~13% despite appropriate antibiotic therapy, suggestive of bacterial persistence and inefficacy of antibiotic regimens. The mechanisms behind bacterial persistence in the host remain unclear, and hence understanding host immunity during persistent B. pseudomallei infections may help designing potential immunotherapy.

    METHODOLOGY/PRINCIPAL FINDINGS: A persistent infection was generated using a small-colony variant (SCV) and a wild-type (WT) B. pseudomallei in BALB/c mice via intranasal administration. Infected mice that survived for >60 days were sacrificed. Lungs, livers, spleens, and peripheral blood mononuclear cells were harvested for experimental investigations. Histopathological changes of organs were observed in the infected mice, suggestive of successful establishment of persistent infections. Moreover, natural killer (NK) cell frequency was increased in SCV- and WT-infected mice. We observed programmed death-1 (PD-1) upregulation on B cells of SCV- and WT-infected mice. Interestingly, PD-1 upregulation was only observed on NK cells and monocytes of SCV-infected mice. In contrast, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) downregulation was seen on NK cells of WT-infected mice, and on monocytes of SCV- and WT-infected mice.

    CONCLUSIONS/SIGNIFICANCE: The SCV and the WT of B. pseudomallei distinctly upregulated PD-1 expression on B cells, NK cells, and monocytes to dampen host immunity, which likely facilitates bacterial persistence. PD-1/PD-L1 pathway appears to play an important role in the persistence of B. pseudomallei in the host.

  19. 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 
  20. Kaur CP, Iyadorai T, Sears C, Roslani AC, Vadivelu J, Samudi C
    Microorganisms, 2023 Feb 09;11(2).
    PMID: 36838407 DOI: 10.3390/microorganisms11020443
    Klebsiella pneumoniae (K. pneumoniae) colonizes the human gut and is a causative factor of pyogenic liver abscess (PLA). Retrospective studies conducted on K. pneumoniae PLA patients revealed subsequent CRC development in later years of their life with increasing prevalence of these strains harbouring polyketide synthase (PKS) genes. To our knowledge there are no known studies directly implicating K. pneumoniae with CRC to date. Our aims are to characterize K. pneumoniae isolates from CRC patients and investigate its effects on cell proliferation in vitro. K. pneumoniae isolates were characterized by screening virulence genes including polyketide synthase (PKS), biofilm assay, antibiotic susceptibility, and string test to determine hypervirulent (hvKp) strains. Solubilised antigens of selected K. pneumoniae isolates were co-cultured with primary colon cell lines and CRC cell lines (Stage I-IV) for 48 h. The enhancement of proliferation was measured through MTT and ECIS assay. Twenty-five percent of K. pneumoniae isolates were PKS-positive out of which 50% were hvKp strains. The majority of the isolates were from the more virulent serotype of K1 (30%) and K2 (50%). PKS-positive K. pneumoniae isolates did not possess genes to confer carbapenem resistance but instead were more highly associated with siderophore genes (aerobactin, enterobactin, and yersiniabactin) and allantoin metabolism genes (allS, allS2). Cell proliferation in primary colon, SW1116 (Stage I), and SW480 (Stage II) CRC cell lines were enhanced when co-cultured with PKS-positive K. pneumoniae antigens. ECIS revealed enhanced cell proliferation upon recurrent antigen exposure. This demonstrates the possible role that PKS-positive K. pneumoniae has in exacerbating CRC progression.
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