Displaying publications 1 - 20 of 155 in total

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  1. 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.
  2. 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.
  3. 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.

  4. Barathan M, Gopal K, Mohamed R, Ellegård R, Saeidi A, Vadivelu J, et al.
    Apoptosis, 2015 Apr;20(4):466-80.
    PMID: 25577277 DOI: 10.1007/s10495-014-1084-y
    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.
  5. Barathan M, Vellasamy KM, Mariappan V, Venkatraman G, Vadivelu J
    PMID: 37773580 DOI: 10.1007/s12010-023-04734-0
    Almost 70% of clinically used antineoplastic drugs are originated from natural products such as plants, marine organism, and microorganisms and some of them are also structurally modified natural products. The naturally occurring drugs may specifically act as inducers of selective cytotoxicity, anti-metastatic, anti-mutagenic, anti-angiogenesis, antioxidant accelerators, apoptosis inducers, autophagy inducers, and cell cycle inhibitors in cancer therapy. Precisely, several reports have demonstrated the involvement of naturally occurring anti-breast cancer drugs in regulating the expression of oncogenic and tumor suppressors associated with carcinogen metabolism and signaling pathways. Anticancer therapies based on nanotechnology have the potential to improve patient outcomes through targeted therapy, improved drug delivery, and combination therapies. This paper has reviewed the current treatment for breast cancer and the potential disadvantages of those therapies, besides the various mechanism used by naturally occurring phytochemicals to induce apoptosis in different types of breast cancer. Along with this, the contribution of nanotechnology in improving the effectiveness of anticancer drugs was also reviewed. With the development of sciences and technologies, phytochemicals derived from natural products are continuously discovered; however, the search for novel natural products as chemoprevention drugs is still ongoing, especially for the advanced stage of breast cancer. Continued research and development in this field hold great promise for advancing cancer care and improving patient outcomes.
  6. Iyer L, Vadivelu J
    Asia Pac J Public Health, 2006;18(3):33-41.
    PMID: 17153080
    The genetic diversity or clonality among Vibrio cholerae O1, O139 and non-O1/ non-O139 of clinical and environmental origin using ribotyping and PFGE was performed in order to ascertain the public health implications of the different genotypes circulating within the Malaysian environment. Using an in-house typing scheme, of the 214 strains included, 202 strains were isolated locally between 1992 and 1998, seven were obtained from Bangladesh and five were reference strains. Amongst the 176 El Tor O1 strains, 152 clinical strains demonstrated five ribotypes--E1a, E1b, E2a, E3 and E1c. E1b was the most predominant ribotype demonstrated by 84% of the El Tor O1 strains and was present in all years demonstrating that this strain was intrinsic to Malaysia. PFGE analysis of these strains demonstrated minimal variation amongst the 15 PFGE profiles obtained. Ribotpye E2a amongst five clinical and two environmental O1 strains, were from one location and had previously been reported in Indonesia and the Philippines, thus demonstrating strong evidence that these strains may have been imported into Malaysia. Among Vibrio cholerae O139 strains, 91.7% were of ribotype A1a similar to the original O139, while two others were of ribotype A1b and one of A1e, corresponding to ribotypes 1, 2 and 3 of Dalsgaard and colleagues' scheme for O139 strains. PFGE analysis demonstrated that 89% of ribotype A1a could be differentiated into three PFGE genotypes which were very closely related. The eight non-O1/non-O139 serogroup strains were heterogeneous in both ribotype and PFGE patterns.
  7. 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.
  8. Lee WC, Anton BP, Wang S, Baybayan P, Singh S, Ashby M, et al.
    BMC Genomics, 2015;16:424.
    PMID: 26031894 DOI: 10.1186/s12864-015-1585-2
    The genome of the human gastric pathogen Helicobacter pylori encodes a large number of DNA methyltransferases (MTases), some of which are shared among many strains, and others of which are unique to a given strain. The MTases have potential roles in the survival of the bacterium. In this study, we sequenced a Malaysian H. pylori clinical strain, designated UM032, by using a combination of PacBio Single Molecule, Real-Time (SMRT) and Illumina MiSeq next generation sequencing platforms, and used the SMRT data to characterize the set of methylated bases (the methylome).
  9. 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.

  10. Khairul Anhar Holder NA, Pallath V, Vadivelu J, Foong CC
    BMC Med Educ, 2023 May 05;23(1):310.
    PMID: 37147649 DOI: 10.1186/s12909-023-04285-2
    BACKGROUND: Academic failure is common among medical schools worldwide. However, the process behind this failure itself is underexplored. A deeper understanding of this phenomenon may avert the vicious cycle of academic failure. Hence, this study investigated the process of academic failure among medical students in Year 1.

    METHODS: This study employed a document phenomenological approach, which is a systematic process to examine documents, interpret them to attain understanding, and develop empirical knowledge of the phenomenon studied. Using document analysis, interview transcripts and reflective essays of 16 Year 1 medical students who experienced academic failure were analysed. Based on this analysis, codes were developed and further reduced into categories and themes. Thirty categories in eight themes were linked to make sense of the series of events leading to academic failure.

    RESULTS: One or more critical incidents commenced during the academic year, which led to possible resulting events. The students had poor attitudes, ineffective learning methods, health problems or stress. Students progressed to mid-year assessments and reacted differently to their results in the assessments. Afterwards, the students tried different types of attempts, and they still failed the end-of-year assessments. The general process of academic failure is illustrated in a diagram describing chronological events.

    CONCLUSION: Academic failure may be explained by a series of events (and consequences) of what students experience and do and how they respond to their experiences. Preventing a preceding event may prevent students from suffering these consequences.

  11. Foong CC, Bashir Ghouse NL, Lye AJ, Khairul Anhar Holder NA, Pallath V, Hong WH, et al.
    BMC Med Educ, 2021 Jun 05;21(1):320.
    PMID: 34090439 DOI: 10.1186/s12909-021-02712-w
    BACKGROUND: Self-regulated learning (SRL) is an important contributing element to the academic success of students. Literature suggests that the understanding of SRL among medical students is obscure as there is still some uncertainty about whether high performing medical students use SRL. This study explored the characteristics of high performing medical students from the SRL perspective to gain a better understanding of the application of SRL for effective learning.

    METHODS: Twenty-one students who scored at the 90th percentile in written knowledge-based assessment consented to participate in this study. Each student wrote a guided reflective journal and subsequently attended a semi-structured interview. Students were prompted to explain the rationales for their answers. The data were then analysed using thematic analysis to identify patterns among these students from the SRL perspective. Two coders analysed the data independently and discussed the codes to reach a consensus.

    RESULTS: High performing students set goals, made plans, and motivated themselves to achieve the goals. They put consistent efforts into their studies and applied effective learning strategies. They also employed coping mechanisms to deal with challenges. High performing students regularly evaluated their performance and adopted new strategies.

    CONCLUSIONS: This study reported that high performing students applied SRL and described the rationales of practice. Medical schools could design SRL-driven interventions to enhance the learning experiences of medical students. Recommendations are made for students on how to apply SRL.

  12. Gopinath V, Saravanan S, Al-Maleki AR, Ramesh M, Vadivelu J
    Biomed Pharmacother, 2018 Nov;107:96-108.
    PMID: 30086465 DOI: 10.1016/j.biopha.2018.07.136
    Natural polysaccharides are renewable with a high degree of biocompatibility, biodegradability, and ability to mimic the natural extracellular matrix (ECM) microenvironment. Comprehensive investigations of polysaccharides are essential for our fundamental understanding of exploiting its potential as bio-composite, nano-conjugate and in pharmaceutical sectors. Polysaccharides are considered to be superior to other polymers, for its ease in tailoring, bio-compatibility, bio-activity, homogeneity and bio-adhesive properties. The main focus of this review is to spotlight the new advancements and challenges concerned with surface modification, binding domains, biological interaction with the conjugate including stability, polydispersity, and biodegradability. In this review, we have limited our survey to three essential polysaccharides including cellulose, starch, and glycogen that are sourced from plants, microbes, and animals respectively are reviewed. We also present the polysaccharides which have been extensively modified with the various types of conjugates for combating last-ditch pharmaceutical challenges.
  13. Barathan M, Mariappan V, Shankar EM, Abdullah BJ, Goh KL, Vadivelu J
    Cell Death Dis, 2013;4:e697.
    PMID: 23807226 DOI: 10.1038/cddis.2013.219
    Photodynamic therapy (PDT) has emerged as a capable therapeutic modality for the treatment of cancer. PDT is a targeted cancer therapy that reportedly leads to tumor cell apoptosis and/or necrosis by facilitating the secretion of certain pro-inflammatory cytokines and expression of multiple apoptotic mediators in the tumor microenvironment. In addition, PDT also triggers oxidative stress that directs tumor cell killing and activation of inflammatory responses. However, the cellular and molecular mechanisms underlying the role of PDT in facilitating tumor cell apoptosis remain ambiguous. Here, we investigated the ability of PDT in association with hypericin (HY) to induce tumor cell apoptosis by facilitating the induction of reactive oxygen species (ROS) and secretion of Th1/Th2/Th17 cytokines in human hepatocellular liver carcinoma cell line (HepG2) cells. To discover if any apoptotic mediators were implicated in the enhancement of cell death of HY-PDT-treated tumor cells, selected gene profiling in response to HY-PDT treatment was implemented. Experimental results showed that interleukin (IL)-6 was significantly increased in all HY-PDT-treated cells, especially in 1 μg/ml HY-PDT, resulting in cell death. In addition, quantitative real-time PCR analysis revealed that the expression of apoptotic genes, such as BH3-interacting-domain death agonist (BID), cytochrome complex (CYT-C) and caspases (CASP3, 6, 7, 8 and 9) was remarkably higher in HY-PDT-treated HepG2 cells than the untreated HepG2 cells, entailing that tumor destruction of immune-mediated cell death occurs only in PDT-treated tumor cells. Hence, we showed that HY-PDT treatment induces apoptosis in HepG2 cells by facilitating cytotoxic ROS, and potentially recruits IL-6 and apoptosis mediators, providing additional hints for the existence of alternative mechanisms of anti-tumor immunity in hepatocellular carcinoma, which contribute to long-term suppression of tumor growth following PDT.
  14. Barathan M, Mohamed R, Vadivelu J, Chang LY, Vignesh R, Krishnan J, et al.
    Cell Immunol, 2017 03;313:1-9.
    PMID: 28104239 DOI: 10.1016/j.cellimm.2016.12.002
    Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence.
  15. Al-Maleki AR, Loke MF, Lui SY, Ramli NSK, Khosravi Y, Ng CG, et al.
    Cell. Microbiol., 2017 12;19(12).
    PMID: 28776327 DOI: 10.1111/cmi.12771
    Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA "on" and "off" motifs. Proteomics analysis was performed on AGS cell pre-infection and postinfection with H. pylori oipA "on" and "off" strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down-regulated postinfection with oipA "off" strains comparing to oipA "on" strains. Furthermore, oipA "off" and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell-cycle arrest than oipA "on" strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of H. pylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA "on" strains predominates.
  16. 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.
  17. 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.
  18. Chua EG, Wise MJ, Khosravi Y, Seow SW, Amoyo AA, Pettersson S, et al.
    DNA Res, 2017 Feb 01;24(1):37-49.
    PMID: 27803027 DOI: 10.1093/dnares/dsw046
    Helicobacter pylori is a highly successful gastric pathogen. High genomic plasticity allows its adaptation to changing host environments. Complete genomes of H. pylori clinical isolate UM032 and its mice-adapted serial derivatives 298 and 299, generated using both PacBio RS and Illumina MiSeq sequencing technologies, were compared to identify novel elements responsible for host-adaptation. The acquisition of a jhp0562-like allele, which encodes for a galactosyltransferase, was identified in the mice-adapted strains. Our analysis implies a new β-1,4-galactosyltransferase role for this enzyme, essential for Ley antigen expression. Intragenomic recombination between babA and babB genes was also observed. Further, we expanded on the list of candidate genes whose expression patterns have been mediated by upstream homopolymer-length alterations to facilitate host adaption. Importantly, greater than four-fold reduction of mRNA levels was demonstrated in five genes. Among the down-regulated genes, three encode for outer membrane proteins, including BabA, BabB and HopD. As expected, a substantial reduction in BabA protein abundance was detected in mice-adapted strains 298 and 299 via Western analysis. Our results suggest that the expression of Ley antigen and reduced outer membrane protein expressions may facilitate H. pylori colonisation of mouse gastric epithelium.
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