Displaying publications 1 - 20 of 153 in total

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  1. Sidahmed HM, Abdelwahab SI, Mohan S, Abdulla MA, Mohamed Elhassan Taha M, Hashim NM, et al.
    PMID: 23634169 DOI: 10.1155/2013/450840
    Cratoxylum arborescens (Vahl) Blume is an Asian herbal medicine with versatile ethnobiological properties including treatment of gastric ulcer. This study evaluated the antiulcerogenic mechanism(s) of α -mangostin (AM) in a rat model of ulcer. AM is a prenylated xanthone derived through biologically guided fractionation of C. arborescens. Rats were orally pretreated with AM and subsequently exposed to acute gastric lesions induced by ethanol. Following treatment, ulcer index, gastric juice acidity, mucus content, histological and immunohistochemical analyses, glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and nonprotein sulfhydryl groups (NP-SH) were evaluated. The anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitory effect, and antioxidant activity of AM were also investigated in vitro. AM (10 and 30 mg/kg) inhibited significantly (P < 0.05) ethanol-induced gastric lesions by 66.04% and 74.39 %, respectively. The compound induces the expression of Hsp70, restores GSH levels, decreases lipid peroxidation, and inhibits COX-2 activity. The minimum inhibitory concentration (MIC) of AM showed an effective in vitro anti-H. pylori activity. The efficacy of the AM was accomplished safely without presenting any toxicological parameters. The results of the present study indicate that the antioxidant properties and the potent anti-H. pylori, in addition to activation of Hsp70 protein, may contribute to the gastroprotective activity of α -mangostin.
  2. 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.
  3. Cheok YY, Tan GMY, Fernandez KC, Chan YT, Lee CYQ, Cheong HC, et al.
    Front Immunol, 2021;12:702156.
    PMID: 34707599 DOI: 10.3389/fimmu.2021.702156
    Podoplanin (Pdpn) is a mucin-type transmembrane protein that has been implicated in multiple physiological settings including lymphangiogenesis, platelet aggregation, and cancer metastasis. Here, we reported an absence of Pdpn transcript expression in the resting mouse monocytic macrophages, RAW264.7 cells; intriguingly, a substantial upregulation of Pdpn was observed in activated macrophages following Helicobacter pylori or lipopolysaccharide stimulation. Pdpn-knockout macrophages demonstrated intact phagocytic and intracellular bactericidal activities comparable to wild type but exhibited impaired migration due to attenuated filopodia formation. In contrast, an ectopic expression of Pdpn augmented filopodia protrusion in activated macrophages. NanoString analysis uncovered a close dependency of Filamin C gene on the presence of Pdpn, highlighting an involvement of Filamin C in modulation of actin polymerization activity, which controls cell filopodia formation and migration. In addition, interleukin-1β production was significantly declined in the absence of Pdpn, suggesting a role of Pdpn in orchestrating inflammation during H. pylori infection besides cellular migration. Together, our findings unravel the Pdpn network that modulates movement of active macrophages.
  4. 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.
  5. Thevakumar K, Chandren JR, Perez-Perez GI, Chua EG, Teh LK, Salleh MZ, et al.
    PLoS One, 2016;11(7):e0159830.
    PMID: 27441568 DOI: 10.1371/journal.pone.0159830
    The epidemiology of Helicobacter pylori (H. pylori) infection is related to human poverty with marked differences between developing and developed countries. Socioeconomic factors and living standards are the main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. The aim of this study was to assess the risk and sero-prevalence of H. pylori colonization among Orang Asli in Peninsula Malaysia. This cross-sectional study was conducted on Orang Asli subjects in seven isolated settlements spanning across all three major tribes (Negrito, Proto Malay and Senoi) in Malaysia. Socio-demographic characteristics of the subjects were obtained through interview. Subjects were tested for H. pylori colonization based on CagA and whole cell (WC) antigen serological assays. A total of 275 subjects participated in this study. Among these subjects, 115 (44.7%) were H. pylori sero-positive with highest sero-prevalence among Negrito (65.7%). Among subjects who were H. pylori sero-positive, CagA sero positivity was also significantly higher among Negrito. The highest proportion of respondents reported to be H. pylori sero-positive was from age group 30 years old and below (57.9%), males (56.2%), Negrito (48.6%) and live in bamboo house (92.3%). The highest proportion of respondents reported to be CagA sero-positive was from age group 30 years old and below (41.4%), males (35.6%) and Negrito (48.6%). The results of this study demonstrate that H. pylori colonization can be related to age, gender, tribes and house materials and CagA sero-positive stain closely associated with age, gender and tribes.
  6. Chow TK, Eu LC, Chin KF, Ong KC, Pailoor J, Vadivelu J, et al.
    Am J Trop Med Hyg, 2016 Mar 2;94(3):522-4.
    PMID: 26787155 DOI: 10.4269/ajtmh.15-0774
    We report a rare case of an asymptomatic latent melioidosis lesion in a posttraumatic splenectomy specimen from a diabetic patient. The 2-cm yellowish, lobulated lesion was found in the splenic parenchyma well away from the traumatized areas. Microscopically, it consisted of a central area of necrosis and exudate surrounded by macrophages, epithelioid cells, lymphocytes, and occasional multinucleated giant cells. Burkholderia bacilli were detected by a novel in situ hybridization (ISH) assay, and confirmed by polymerase chain reaction and sequencing to be Burkholderia pseudomallei. As melioidosis was not suspected initially, bacterial culture was not done but electron microscopy showed morphologically viable and dividing bacilli in the lesion. Moreover, the surgical wound became infected with B. pseudomallei several days post-surgery. After treatment with ceftazidime and trimethoprim/sulfamethoxazole, the wound infection cleared. We believe this could be a unique case of asymptomatic latent melioidosis in the spleen. In endemic countries, chronic granulomas should be investigated for B. pseudomallei infection, and if available, ISH may be helpful for diagnosis.
  7. 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.

  8. Eu LC, Ong KC, Hiu J, Vadivelu J, Nathan S, Wong KT
    Mod Pathol, 2014 May;27(5):657-64.
    PMID: 24186135 DOI: 10.1038/modpathol.2013.184
    Burkholderia pseudomallei causes a potentially fatal infection called melioidosis. We have developed a nonfluorescent, colorimetric in situ hybridization assay using a specific probe to target 16s rRNA of B. pseudomallei in formalin-fixed, paraffin-embedded infected tissues for diagnostic purposes and to study infectious disease pathology. A 63-base pair DNA probe was synthesized and labeled with digoxigenin by PCR. Probe specificity was confirmed by BLAST analysis and by testing on appropriate microbial controls. The in situ hybridization assay was specifically and consistently positive for B. pseudomallei, showing strongly and crisply stained, single bacillus and bacilli clusters in mainly inflamed tissues in seven human acute melioidosis cases and experimentally infected mouse tissues. Intravascular and extravascular bacilli were detected in both intracellular and extracellular locations in various human organs, including lung, spleen, kidney, liver, bone marrow, and aortic mycotic aneurysm, particularly in the inflamed areas. Intravascular, intracellular bacteria in melioidosis have not been previously reported. Although the identity of infected intravascular leukocytes has to be confirmed, extravascular, intracellular bacilli appear to be found mainly within macrophages and neutrophils. Rarely, large intravascular, extracellular bacillary clusters/emboli could be detected in both human and mouse tissues. B. cepacia and non-Burkholderia pathogens (16 microbial species) all tested negative. Nonpathogenic B. thailandensis showed some cross-hybridization but signals were less intense. This in situ hybridization assay could be usefully adapted for B. pseudomallei identification in other clinical specimens such as pus and sputum.
  9. Choo SW, Ang MY, Fouladi H, Tan SY, Siow CC, Mutha NV, et al.
    BMC Genomics, 2014;15:600.
    PMID: 25030426 DOI: 10.1186/1471-2164-15-600
    Helicobacter is a genus of Gram-negative bacteria, possessing a characteristic helical shape that has been associated with a wide spectrum of human diseases. Although much research has been done on Helicobacter and many genomes have been sequenced, currently there is no specialized Helicobacter genomic resource and analysis platform to facilitate analysis of these genomes. With the increasing number of Helicobacter genomes being sequenced, comparative genomic analysis on members of this species will provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of diseases caused by Helicobacter pathogens.
  10. Chua EG, Debowski AW, Webberley KM, Peters F, Lamichhane B, Loke MF, et al.
    Gastroenterol Rep (Oxf), 2019 Feb;7(1):42-49.
    PMID: 30792865 DOI: 10.1093/gastro/goy048
    Background: Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection. Hence, the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals. Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H. pylori. However, metronidazole resistance can also arise in H. pylori strains expressing functional RdxA protein, suggesting that there are other mechanisms that may confer resistance to this drug.

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

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

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

  11. Rafieerad AR, Bushroa AR, Nasiri-Tabrizi B, Kaboli SHA, Khanahmadi S, Amiri A, et al.
    J Mech Behav Biomed Mater, 2017 May;69:1-18.
    PMID: 28027481 DOI: 10.1016/j.jmbbm.2016.11.019
    Recently, the robust optimization and prediction models have been highly noticed in district of surface engineering and coating techniques to obtain the highest possible output values through least trial and error experiments. Besides, due to necessity of finding the optimum value of dependent variables, the multi-objective metaheuristic models have been proposed to optimize various processes. Herein, oriented mixed oxide nanotubular arrays were grown on Ti-6Al-7Nb (Ti67) implant using physical vapor deposition magnetron sputtering (PVDMS) designed by Taguchi and following electrochemical anodization. The obtained adhesion strength and hardness of Ti67/Nb were modeled by particle swarm optimization (PSO) to predict the outputs performance. According to developed models, multi-objective PSO (MOPSO) run aimed at finding PVDMS inputs to maximize current outputs simultaneously. The provided sputtering parameters were applied as validation experiment and resulted in higher adhesion strength and hardness of interfaced layer with Ti67. The as-deposited Nb layer before and after optimization were anodized in fluoride-base electrolyte for 300min. To crystallize the coatings, the anodically grown mixed oxide TiO2-Nb2O5-Al2O3 nanotubes were annealed at 440°C for 30min. From the FESEM observations, the optimized adhesive Nb interlayer led to further homogeneity of mixed nanotube arrays. As a result of this surface modification, the anodized sample after annealing showed the highest mechanical, tribological, corrosion resistant and in-vitro bioactivity properties, where a thick bone-like apatite layer was formed on the mixed oxide nanotubes surface within 10 days immersion in simulated body fluid (SBF) after applied MOPSO. The novel results of this study can be effective in optimizing a variety of the surface properties of the nanostructured implants.
  12. Selvarajoo S, Liew JWK, Tan W, Lim XY, Refai WF, Zaki RA, et al.
    Sci Rep, 2020 06 12;10(1):9534.
    PMID: 32533017 DOI: 10.1038/s41598-020-66212-5
    Dengue has become a global public health problem. Despite reactive efforts by the government in Malaysia, the dengue cases are on the increase. Adequate knowledge, positive attitude and correct practice for dengue control are essential to stamp out the disease. Hence, this study aims to assess the factors associated with dengue knowledge, attitude and practice (KAP), as well as the association with dengue IgM and IgG seropositivity. A community-based cross-sectional study was conducted in a closed, dengue endemic area with multi-storey dwellings . Five hundred individuals (aged 18 years and above) were approached for pre-tested KAP and seroprevalences assessment. The study showed only half of the total participants have good knowledge (50.7%) but they had insufficient knowledge about dengue during pregnancy. 53.2% of people had poor attitude and 50.2% reported poor practice for dengue control. Out of 85 respondents who agreed to participate in the dengue seroprevalence study, 74.1% (n = 63) were positive for dengue IgG and 7.1% (n = 6) were positive for dengue IgM. Among all sociodemographic variable, race is the only independent predicator for all KAP levels (P 
  13. Zulkefli NJ, Teh CSJ, Mariappan V, Ngoi ST, Vadivelu J, Ponnampalavanar S, et al.
    PLoS One, 2021;16(12):e0261382.
    PMID: 34910764 DOI: 10.1371/journal.pone.0261382
    Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form small colony variants (SCVs) as part of the adaptive features in response to environmental stress. In this study, we characterize the genomic characteristics, antimicrobial resistance (AMR), and metabolic phenotypes of B. pseudomallei SCV and wild type (WT) strains. Whole-genome sequence analysis was performed to characterize the genomic features of two SCVs (CS and OS) and their respective parental WT strains (CB and OB). Phylogenetic relationship between the four draft genomes in this study and 19 publicly available genomes from various countries was determined. The four draft genomes showed a close phylogenetic relationship with other genomes from Southeast Asia. Broth microdilution and phenotype microarray were conducted to determine the AMR profiles and metabolic features (carbon utilization, osmolytes sensitivity, and pH conditions) of all strains. The SCV strains exhibited identical AMR phenotype with their parental WT strains. A limited number of AMR-conferring genes were identified in the B. pseudomallei genomes. The SCVs and their respective parental WT strains generally shared similar carbon-utilization profiles, except for D,L-carnitine (CS), g-hydroxybutyric acid (OS), and succinamic acid (OS) which were utilized by the SCVs only. No difference was observed in the osmolytes sensitivity of all strains. In comparison, WT strains were more resistant to alkaline condition, while SCVs showed variable growth responses at higher acidity. Overall, the genomes of the colony morphology variants of B. pseudomallei were largely identical, and the phenotypic variations observed among the different morphotypes were strain-specific.
  14. Zulpa AK, Barathan M, Iyadorai T, Mariappan V, Vadivelu J, Teh CSJ, et al.
    World J Microbiol Biotechnol, 2023 Oct 06;39(12):333.
    PMID: 37801157 DOI: 10.1007/s11274-023-03767-1
    pks+ Escherichia coli (E. coli) triggers genomic instability in normal colon cells which leads to colorectal cancer (CRC) tumorigenesis. Previously, we reported a significant presentation of pks+ E. coli strains in CRC patients' biopsies as compared to healthy cohorts. In this work, using an in vitro infection model, we further explored the ability of these strains in modulating cell cycle arrest and activation of apoptotic mediators in both primary colon epithelial cells (PCE) and CRC cells (HCT-116). Sixteen strains, of which eight tumours and the matching non-malignant tissues, respectively, from eight pks+ E. coli CRC patients were subjected to BrDU staining and cell cycle analysis via flow cytometry, while a subset of these strains underwent analysis of apoptotic mediators including caspase proteins, cellular reactive oxygen species (cROS) and mitochondrial membrane potential (MMP) via spectrophotometry as well as proinflammatory cytokines via flow cytometry. Data revealed that all strains exerted S-phase cell cycle blockade in both cells and G2/M phase in PCE cells only. Moreover, more significant upregulation of Caspase 9, cROS, proinflammatory cytokines and prominent downregulation of MMP were detected in HCT-116 cells indicating the potential role of pks related bacterial toxin as anticancer agent as compared to PCE cells which undergo cellular senescence leading to cell death without apparent upregulation of apoptotic mediators. These findings suggest the existence of discrepancies underlying the mechanism of action of pks+ E. coli on both cancer and normal cell lines. This work propounds the rationale to further understand the mechanism underlying pks+ E. coli-mediated CRC tumorigenesis and cancer killing.
  15. 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.

  16. 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.
  17. 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.
  18. Khosravi Y, Seow SW, Amoyo AA, Chiow KH, Tan TL, Wong WY, et al.
    Sci Rep, 2015;5:8731.
    PMID: 25736205 DOI: 10.1038/srep08731
    Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted.
  19. Khosravi Y, Vellasamy KM, Mariappan V, Ng SL, Vadivelu J
    ScientificWorldJournal, 2014;2014:132971.
    PMID: 25379514 DOI: 10.1155/2014/132971
    Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to many antibiotics. Ceftazidime (CAZ), the synthetic β-lactam, is normally used as the first-line antibiotic therapy for treatment of melioidosis. However, acquired CAZ resistance can develop in vivo during treatment with CAZ, leading to mortality if therapy is not switched to a different antibiotic(s) in a timely manner. In this study, susceptibilities of 81 B. pseudomallei isolates to nine different antimicrobial agents were determined using the disk diffusion method, broth microdilution test and Etest. Highest percentage of susceptibility was demonstrated to CAZ, amoxicillin/clavulanic acid, meropenem, imipenem, and trimethoprim/sulfamethoxazole. Although these drugs demonstrated the highest percentage of susceptibility in B. pseudomallei, the overall results underline the importance of the emergence of resistance in this organism. PCR results showed that, of the 81 B. pseudomallei, six multidrug resistant (MDR) isolates carried bpeB, amrB, and BPSS1119 and penA genes. Genotyping of the isolates using random amplified polymorphic DNA analysis showed six different PCR fingerprinting patterns generated from the six MDR isolates clusters (A) and eight PCR fingerprinting patterns generated for the remaining 75 non-MDR isolates clusters (B).
  20. Khosravi Y, Dieye Y, Poh BH, Ng CG, Loke MF, Goh KL, et al.
    ScientificWorldJournal, 2014;2014:610421.
    PMID: 25105162 DOI: 10.1155/2014/610421
    Human stomach is the only known natural habitat of Helicobacter pylori (Hp), a major bacterial pathogen that causes different gastroduodenal diseases. Despite this, the impact of Hp on the diversity and the composition of the gastric microbiota has been poorly studied. In this study, we have analyzed the culturable gastric microbiota of 215 Malaysian patients, including 131 Hp positive and 84 Hp negative individuals that were affected by different gastric diseases. Non-Hp bacteria isolated from biopsy samples were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry based biotyping and 16SrRNA sequencing. The presence of Hp did not significantly modify the diversity of the gastric microbiota. However, correlation was observed between the isolation of Streptococci and peptic ulcer disease. In addition, as a first report, Burkholderia pseudomallei was also isolated from the gastric samples of the local population. This study suggested that there may be geographical variations in the diversity of the human gastric microbiome. Geographically linked diversity in the gastric microbiome and possible interactions between Hp and other bacterial species from stomach microbiota in pathogenesis are proposed for further investigations.
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