Displaying publications 1 - 20 of 37 in total

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  1. Mariappan V, Vellasamy KM, Vadivelu J
    Sci Rep, 2017 08 21;7(1):9015.
    PMID: 28827633 DOI: 10.1038/s41598-017-09373-0
    Little is known about the evolution, adaptation and pathogenesis of Burkholderia pseudomallei within host during acute melioidosis infection. Melioidosis is a potential life threatening disease contracted through inhalation, ingestion, inoculation or direct entry of the organism into the blood stream via wounds or skin abrasions from contaminated soil and water. Environmental B. pseudomallei strain (Bp MARAN ), isolated during a melioidosis outbreak in Pahang, Malaysia was injected intra-peritoneally into a mouse and passaged strain was recovered from spleen (Bpmouse-adapted). A gel-based comparative proteomics profiling approach was used, to map and identify differentially expressed proteins (fold-change ≥ 2; p-value ≤ 0.05) between the strains. A total of 730 and 685 spots were visualised in the Bp MARAN and Bpmouse-adapted strains, respectively. Of the 730 spots (Bp MARAN as reference gel), 87 spots were differentially regulated (44 up- and 43 down-regulated). The identified proteins were classified as proteins related to metabolism, stress response, virulence, signal transduction, or adhesion. In comparison, it was found that those proteins related to adhesins, virulence factors and stress- response were up-regulated and could possibly explain the adaptation of the bacteria in the host. Investigating the differentially expressed proteins may provide better perspective of bacterial factors which aid survivability of B. pseudomallei in host.
  2. Ishak B, Azizan ANA, Mariappan V
    Malays J Med Sci, 2022 Oct;29(5):126-132.
    PMID: 36474533 DOI: 10.21315/mjms2022.29.5.13
    BACKGROUND: Many factors determine the success of wearing contact lens, including knowledge and compliance towards lens care. This study aimed to evaluate the level of knowledge and compliance between two groups of adult contact lens wearers in Kuala Lumpur, Malaysia.

    METHODS: A total of 60 participants aged 18-30 years old volunteered to participate in this study (30 participants prescribed contact lenses at the Universiti Kebangsaan Malaysia [UKM] optometry clinic and 30 participants fitted at private practices). Participants were interviewed using a structured questionnaire consisting of nine questions on basic knowledge related to lens wear and 13 questions on compliance, categorised into questions on the cleaning process, disinfection, accessories care and replacement schedule.

    RESULTS: All participants wore disposable contact lens 53.3% (n = 32) participants preferred using monthly disposable lenses. Both groups had the same level of knowledge, except knowledge of the effects of makeup (P < 0.000) and duration of the solution used for cleaning (P < 0.010), showing lack of knowledge on contact lenses among participants in private practices group. There were no significant differences between the groups in terms of the level of compliance with the cleaning process (P = 0.830), disinfection (P = 0.725), accessories care (P = 0.865) and replacement schedule (P = 0.699).

    CONCLUSION: Participants from UKM optometry clinic had better knowledge on wearing contact lens; moreover, both groups had good compliance towards lens care. Contact lens practitioners should provide all the necessary information to contact lens wearers so that they are equipped to handle contact lenses correctly, which would minimise the risk of eye complications.

  3. 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).
  4. Mariappan V, Vellasamy KM, Thimma J, Hashim OH, Vadivelu J
    PLoS One, 2013;8(10):e77418.
    PMID: 24116227 DOI: 10.1371/journal.pone.0077418
    Burkholderia cepacia is an opportunistic human pathogen associated with life-threatening pulmonary infections in immunocompromised individuals. Pathogenesis of B. cepacia infection involves adherence, colonisation, invasion, survival and persistence in the host. In addition, B. cepacia are also known to secrete factors, which are associated with virulence in the pathogenesis of the infection. In this study, the host factor that may be the cause of the infection was elucidated in human epithelial cell line, A549, that was exposed to live B. cepacia (mid-log phase) and its secretory proteins (mid-log and early-stationary phases) using the Illumina Human Ref-8 microarray platform. The non-infection A549 cells were used as a control. Expression of the host genes that are related to apoptosis, inflammation and cell cycle as well as metabolic pathways were differentially regulated during the infection. Apoptosis of the host cells and secretion of pro-inflammatory cytokines were found to be inhibited by both live B. cepacia and its secretory proteins. In contrast, the host cell cycle and metabolic processes, particularly glycolysis/glycogenesis and fatty acid metabolism were transcriptionally up-regulated during the infection. Our microarray analysis provided preliminary insights into mechanisms of B. cepacia pathogenesis. The understanding of host response to an infection would provide novel therapeutic targets both for enhancing the host's defences and repressing detrimental responses induced by the invading pathogen.
  5. Mariappan V, Vellasamy KM, Hashim OH, Vadivelu J
    PLoS One, 2011;6(10):e26518.
    PMID: 22046299 DOI: 10.1371/journal.pone.0026518
    Burkholderia cepacia is a Gram-negative pathogen that causes serious respiratory infections in immunocompromised patients and individuals with cystic fibrosis. This bacterium is known to release extracellular proteins that may be involved in virulence.
  6. Vellasamy KM, Mariappan V, Hashim OH, Vadivelu J
    Electrophoresis, 2011 Jan;32(2):310-20.
    PMID: 21254130 DOI: 10.1002/elps.201000355
    Bacterial secreted proteins are known to be involved in virulence and may mediate important host-pathogen interactions. In this study, when the stationary phase culture supernatant of Burkholderia pseudomallei was subjected to 2-DE, 113 protein spots were detected. Fifty-four of the secreted proteins, which included metabolic enzymes, transcription/translation regulators, potential virulence factors, chaperones, transport regulators, and hypothetical proteins, were identified using MS and database search. Twelve of these proteins were apparently reactive to antisera of mice that were immunised with B. pseudomallei secreted proteins. These proteins might be excellent candidates to be used as diagnostic markers or putative candidate vaccines against B. pseudomallei infections.
  7. Jubaidi FF, Zainalabidin S, Mariappan V, Budin SB
    Int J Mol Sci, 2020 Aug 22;21(17).
    PMID: 32842567 DOI: 10.3390/ijms21176043
    As the powerhouse of the cells, mitochondria play a very important role in ensuring that cells continue to function. Mitochondrial dysfunction is one of the main factors contributing to the development of cardiomyopathy in diabetes mellitus. In early development of diabetic cardiomyopathy (DCM), patients present with myocardial fibrosis, dysfunctional remodeling and diastolic dysfunction, which later develop into systolic dysfunction and eventually heart failure. Cardiac mitochondrial dysfunction has been implicated in the development and progression of DCM. Thus, it is important to develop novel therapeutics in order to prevent the progression of DCM, especially by targeting mitochondrial dysfunction. To date, a number of studies have reported the potential of phenolic acids in exerting the cardioprotective effect by combating mitochondrial dysfunction, implicating its potential to be adopted in DCM therapies. Therefore, the aim of this review is to provide a concise overview of mitochondrial dysfunction in the development of DCM and the potential role of phenolic acids in combating cardiac mitochondrial dysfunction. Such information can be used for future development of phenolic acids as means of treating DCM by alleviating the cardiac mitochondrial dysfunction.
  8. Vellasamy KM, Mariappan V, Shankar EM, Vadivelu J
    PLoS Negl Trop Dis, 2016 07;10(7):e0004730.
    PMID: 27367858 DOI: 10.1371/journal.pntd.0004730
    BACKGROUND: Burkholderia pseudomallei, the causative agent of melioidosis poses a serious threat to humankind. B. pseudomallei secretes numerous virulence proteins that alter host cell functions to escape from intracellular immune sensors. However, the events underlying disease pathogenesis are poorly understood.

    METHODS: We determined the ability of B. pseudomallei to invade and survive intracellularly in A549 human lung epithelial cells, and also investigated the early transcriptional responses using an Illumina HumanHT-12 v4 microarray platform, after three hours of exposure to live B. pseudomallei (BCMS) and its secreted proteins (CCMS).

    RESULTS: We found that the ability of B. pseudomallei to invade and survive intracellularly correlated with increase of multiplicity of infection and duration of contact. Activation of host carbohydrate metabolism and apoptosis as well as suppression of amino acid metabolism and innate immune responses both by live bacteria and its secreted proteins were evident. These early events might be linked to initial activation of host genes directed towards bacterial dissemination from lungs to target organs (via proposed in vivo mechanisms) or to escape potential sensing by macrophages.

    CONCLUSION: Understanding the early responses of A549 cells toward B. pseudomallei infection provide preliminary insights into the likely pathogenesis mechanisms underlying melioidosis, and could contribute to development of novel intervention strategies to combat B. pseudomallei infections.

  9. Mariappan V, Thimma J, Vellasamy KM, Shankar EM, Vadivelu J
    Environ Microbiol Rep, 2018 04;10(2):217-225.
    PMID: 29393577 DOI: 10.1111/1758-2229.12624
    Physiological constituents in airway surface liquids (ASL) appear to impact the adherence and invasion potentials of Burkholderia pseudomallei contributing to recrudescent melioidosis. Here, we investigated the factors present in ASL that is likely to influence bacterial adhesion and invasion leading to improved understanding of bacterial pathogenesis. Six B. pseudomallei clinical isolates from different origins were used to investigate the ability of the bacteria to adhere and invade A549 human lung epithelial cells using a system that mimics the physiological ASL with different pH, NaCl, KCl, CaCl2 and glucose concentrations. These parameters resulted in markedly differential adherence and invasion abilities of B. pseudomallei to the lung epithelial cells. The concentration of 20 mM glucose dramatically increased adherence and invasion by increasing the rate of pili formation in depiliated bacteria. Glucose significantly increased adherence and invasion of B. pseudomallei to A549 cells, and presence of NaCl, KCl and CaCl2 markedly ablated the effect despite the presence of glucose. Our data established a link between glucose, enhanced adhesion and invasion potentials of B. pseudomallei, hinting increased susceptibility of individuals with diabetes mellitus to clinical melioidosis.
  10. Mariappan V, Vellasamy KM, Mohamad NA, Subramaniam S, Vadivelu J
    Front Microbiol, 2021;12:718774.
    PMID: 34759896 DOI: 10.3389/fmicb.2021.718774
    On a global scale, antimicrobial resistance (AMR) is recognized as a One Health challenge due to the continual and increased development and distribution of resistant microbes and genes among humans, animals, and the environment. These sectors contribute to the increase in AMR, as antibiotics are widely used in healthcare to treat or prevent bacterial infection; as growth enhancers, therapeutics and metaphylactics in animal husbandry; and transmitted in the environment through irrigation using wastewater or inappropriate disposal and treatment of human and agricultural waste. However, there is a major drawback in terms of the lack of research assessing the coexistence of AMR in these sectors. Extensive research highlighted food-animal manufacture structures that are likely to harbor reservoirs or promote transmission of AMR, in addition to increasing human colonization with AMR commensal bacteria. Numerous antibiotic stewardship policies have been designed and implemented in medical practices and animal husbandry in high- and middle-income countries. However, research concentrating on high-income settings, attitudes, emotions, and beliefs on the utilization of antimicrobials remain underexplored in lower- and middle-income countries such as Malaysia. Microbiological, epidemiological, and social science exploration are required at community and farming across the One Health range to fill huge gaps in information and knowledge of AMR. Manipulating human activities and character associated with antibiotics is a multifaceted progression that includes elements like knowledge, social behavior, attitudes, approaches, social standards, socioeconomic settings, peer pressure, experiences, and biophysical environment. Therefore, understanding these aspects in the utilization of antimicrobial drugs among the different sectors is essential to develop and implement policies to curb AMR development and transmission that overarch all sectors within the One Health consortium in Malaysia.
  11. Barathan M, Vellasamy KM, Mariappan V, Venkatraman G, Vadivelu J
    Appl Biochem Biotechnol, 2024 Jul;196(7):4644-4660.
    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.
  12. Al-Maleki AR, Mariappan V, Vellasamy KM, Shankar EM, Tay ST, Vadivelu J
    J Proteomics, 2014 Jun 25;106:205-20.
    PMID: 24742602 DOI: 10.1016/j.jprot.2014.04.005
    Colony morphology variation is a characteristic of Burkholderia pseudomallei primary clinical isolates, associated with variations in expression of virulence factors. Here, we performed comparative investigations on adhesion, invasion, plaque-forming abilities and protein profiles of B. pseudomallei wild-type (WT) and a small colony variant (SCV). The percentage of SCV adherence to A549 cells was significantly higher (2.73%) than WT (1.91%). In contrast, WT was significantly more efficient (0.63%) than SCV (0.31%) in invasiveness and in inducing cellular damage. Using 2-DE and MALDI TOF/TOF, 263 and 258 protein spots were detected in WT and SCV, respectively. Comparatively, 49 proteins were differentially expressed in SCV when compared with WT. Of these, 31 proteins were up-regulated, namely, nucleoside diphosphate kinase (Ndk), phosphoglycerate kinase (Pgk), thioredoxin (TrxA), putative ferritin DPS-family DNA-binding protein (DPS) and oxidoreductase (AhpC) that are known to be involved in adhesion, intracellular survival and persistence. However, among the 18 down-regulated proteins, enolase (Eno), elongation factor (EF-Tu) and universal stress-related proteins were associated with invasion and virulence. Differences observed in these protein profiles provide ample clues to their association with the morphotypic and phenotypic characteristics of colony variants, providing additional insights into the potential association of B. pseudomallei colony morphotypes with disease pathogenesis.
  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. Mariappan V, Vellasamy KM, Thimma JS, Hashim OH, Vadivelu J
    Vaccine, 2010 Feb 3;28(5):1318-24.
    PMID: 19944788 DOI: 10.1016/j.vaccine.2009.11.027
    Burkholderia cepacia is an opportunistic human pathogen associated with lung infections. Secretory proteins of B. cepacia are known to be involved in virulence and may mediate important host-pathogen interactions. In the present study, secretory proteins isolated from B. cepacia culture supernatant were separated using two-dimensional gel electrophoresis, followed by Western blot analysis to identify the immunogenic proteins. Mice antibodies raised to B. cepacia inactivated whole bacteria, outer membrane protein and culture filtrate antigen detected 74, 104 and 32 immunogenic proteins, respectively. Eighteen of these immunogenic proteins which reacted with all three antibodies were identified and might be potential molecules as a diagnostic marker or a putative candidate vaccine against B. cepacia infections.
  15. 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.
  16. 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.

  17. 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.
  18. 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.
  19. 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.

  20. 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.
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