Displaying publications 1 - 20 of 33 in total

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  1. 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.

    Matched MeSH terms: Lung/microbiology
  2. 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.

    Matched MeSH terms: Lung/microbiology
  3. 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.
    Matched MeSH terms: Lung/microbiology
  4. 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.
    Matched MeSH terms: Lung/microbiology
  5. Nyanti LE, Kho SS, Tie ST
    Med J Malaysia, 2019 02;74(1):79-81.
    PMID: 30846667
    Primary lung malignancy presenting as empyema is rare, with a reported incidence of 0.3%. We report a case of a 60- year-old man presenting with unilateral pleural effusion; diagnostic thoracocentesis confirmed Salmonella empyema. Post-drainage, chest radiograph showed persisting right hemithorax opacity; subsequent computed tomography revealed a right lung mass with right upper lobe bronchus obliteration. Percutaneous biopsy confirmed advanced stage lung adenocarcinoma. We discuss the mechanism of post-obstructive pneumonia in lung cancerassociated empyema and the utility of bedside ultrasound in diagnosis of lung masses. Clinicians are alerted to the possibility of lung malignancy in elderly patients presenting with empyema.
    Matched MeSH terms: Lung/microbiology
  6. Tan RZ, Mohd Nor F, Shafie S, Tan LJ
    Forensic Sci Med Pathol, 2019 03;15(1):151-154.
    PMID: 30293222 DOI: 10.1007/s12024-018-0026-3
    Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a gram-negative intracellular bacillus. Tuberculosis, also an infectious disease, is caused by Mycobacterium tuberculosis, an acid fast bacillus. In both diseases, patients commonly present with fever and respiratory symptoms due to sepsis which might lead to respiratory failure or sudden death if left untreated. Not only are these two entities similar in clinical presentation, but the autopsy findings may mimic each other, giving rise to difficulties in determining the cause of death. We report a case of melioidosis and compare it to a typical case of miliary tuberculosis. Similarities between the cases on gross and histopathological examinations are discussed. In such circumstances, microbiological culture of bodily fluids and internal organs should be performed to ascertain the correct cause of death.
    Matched MeSH terms: Lung/microbiology
  7. Muda Z, Ibrahim H, Abdulrahman EJ, Menon BS, Zahari Z, Zaleha AM, et al.
    Med J Malaysia, 2008 Dec;63(5):415-6.
    PMID: 19803305 MyJurnal
    Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.
    Matched MeSH terms: Lung/microbiology
  8. Davidson RM, Hasan NA, de Moura VC, Duarte RS, Jackson M, Strong M
    Infect Genet Evol, 2013 Dec;20:292-7.
    PMID: 24055961 DOI: 10.1016/j.meegid.2013.09.012
    Rapidly growing, non-tuberculous mycobacteria (NTM) in the Mycobacterium abscessus (MAB) species are emerging pathogens that cause various diseases including skin and respiratory infections. The species has undergone recent taxonomic nomenclature refinement, and is currently recognized as two subspecies, M. abscessus subsp. abscessus (MAB-A) and M. abscessus subsp. bolletii (MAB-B). The recently reported outbreaks of MAB-B in surgical patients in Brazil from 2004 to 2009 and in cystic fibrosis patients in the United Kingdom (UK) in 2006 to 2012 underscore the need to investigate the genetic diversity of clinical MAB strains. To this end, we sequenced the genomes of two Brazilian MAB-B epidemic isolates (CRM-0019 and CRM-0020) derived from an outbreak of skin infections in Rio de Janeiro, two unrelated MAB strains from patients with pulmonary infections in the United States (US) (NJH8 and NJH11) and one type MAB-B strain (CCUG 48898) and compared them to 25 publically available genomes of globally diverse MAB strains. Genome-wide analyses of 27,598 core genome single nucleotide polymorphisms (SNPs) revealed that the two Brazilian derived CRM strains are nearly indistinguishable from one another and are more closely related to UK outbreak isolates infecting CF patients than to strains from the US, Malaysia or France. Comparative genomic analyses of six closely related outbreak strains revealed geographic-specific large-scale insertion/deletion variation that corresponds to bacteriophage insertions and recombination hotspots. Our study integrates new genome sequence data with existing genomic information to explore the global diversity of infectious M. abscessus isolates and to compare clinically relevant outbreak strains from different continents.
    Matched MeSH terms: Lung/microbiology*
  9. Zamri-Saad M, Effendy WM, Maswati MA, Salim N, Sheikh-Omar AR
    Br. Vet. J., 1996 Jul;152(4):453-8.
    PMID: 8791853
    A model of pneumonic pasteurellosis has been established in goats using Pasteurella multocida harvested from pneumonic lungs of goats (types A and D), rabbits (type A) and sheep (type D). The resultant infections were acute, subacute or chronic. The gross and histological lesions of the subacute and chronic infections were typical of pneumonic pasteurellosis. P. multocida type D produced significantly (P < 0.01) more severe lesions when compared with other isolates. There were strong correlations between the clinical signs and the severity of lesions.
    Matched MeSH terms: Lung/microbiology
  10. Al-Haddawi MH, Jasni S, Zamri-Saad M, Mutalib AR, Son R, Sheikh-Omar AR
    Vet Res Commun, 2000 Apr;24(3):153-67.
    PMID: 10836274
    Sixteen 8- to 9-week-old Pasteurella multocida-free rabbits were divided into two equal groups. Eight rabbits in one group were inoculated intranasally with P. multoida type A:3. The other eight were inoculated intranasally with phosphate-buffered saline and used as controls. Nasal swabs taken before and after inoculation were cultured for bacterial isolation. Post-mortem nasal swabs and lung samples were cultured for bacteriological isolation. Nasal mucosa and lung samples were collected and processed for transmission electron microscopy. Pasteurella multocida was isolated from the nasal cavity of all infected rabbits and from the lungs of four infected rabbits. Degenerative ultrastructural changes in epithelial cells and endothelial cells were seen in the infected rabbits. Deciliation of the ciliated epithelium and hyperplasia of the goblet cells in the nasal mucosa were noted. Thickening of the alveolar septa due to hyperplasia of type II pneumocytes, swelling of the endothelial lining of capillaries and infiltration of inflammatory cells were also observed. Intracellular invasion of the nasal epithelial cells and of type II pneumocytes by the organism was observed. Coccobacilli were observed in membrane-bound vacuoles in the cytoplasm of these cells. The vacuoles were adjacent to the host-cell mitochondria and some of these vacuoles appeared to be fused to the mitochondrial membrane. Some type I pneumocytes with intracellular membrane-bound vacuoles containing bacterial cells showed protrusions, which appeared to detach into the alveolar lumina. These results indicated that P. multocida serotype A:3 in rabbits can invade the epithelial cell and cause structural changes in the interstitium, epithelium and endothelium. Heterophils and macrophages appear to play important roles in tissue injury.
    Matched MeSH terms: Lung/microbiology*
  11. Al-Haddawi MH, Jasni S, Zamri-Saad M, Mutalib AR, Zulkifli I, Son R, et al.
    Vet J, 2000 May;159(3):274-81.
    PMID: 10775473
    In vitro experiments were undertaken to study the adhesion and colonization to tracheal mucosa, lung and aorta explants from freshly killed rabbits of two different strains of Pasteurella multocida. Serotype A:3 (capsulated, fimbriae +, haemagglutination -, dermonecrotic toxin -) isolated from a rabbit with rhinitis, and serotype D:1 (non-capsulated, fimbriae +, haemagglutination +, dermonecrotic toxin +) isolated from a dead rabbit with septicaemia, were used. When the explants were observed under the scanning electron microscope, the type D strain was highly adherent to trachea and aorta explants compared to the type A strain. Adhesion to lung explants was best achieved by the type A strain after 45 min incubation, but after 2 h incubation no significant difference was observed between the strains. Our data indicate that the presence of fimbriae and the absence of capsule seem to enhance the adherence of P. multocida type D strain to tracheal tissue. The capsular material of P. multocida type A strain and the toxin of the type D strain seem to influence the adherence to lung tissue in rabbit. Adhesion of strain D to aorta may indicate the expression of receptors on the endothelium to that strain and may also explain the ability of certain strains to cause septicaemia.
    Matched MeSH terms: Lung/microbiology
  12. 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.
    Matched MeSH terms: Lung/microbiology
  13. Rosdina Z, Nurul Yaqeen ME, Hanafiah M, Nor Salmah B
    Med J Malaysia, 2017 04;72(2):147-149.
    PMID: 28473686 MyJurnal
    We report a case of a 34-year-old man who was initially treated as community acquired pneumonia following a three-month-history of productive cough, loss of weight and loss of appetite. However, three months after discharged from the hospital, he presented again with worsening respiratory symptoms and radiological evidence of a lung cavitation with intracavitary lesion resembling an aspergilloma associated with surrounding consolidation. Unfortunately, he remained symptomatic despite on antifungal therapy. The repeat computed-tomography demonstrated persistent cavitating lesion with development of necrotising pneumonia. He underwent lobectomy and the histopathological analysis of the resected specimen however revealed the diagnosis of actinomycosis.
    Matched MeSH terms: Lung/microbiology
  14. Menon BS, Shuaib IL, Zamari M, Haq JA, Aiyar S, Noh LM
    Ann Trop Paediatr, 1998 Mar;18(1):45-8.
    PMID: 9692001
    We describe a Malay girl with disseminated cryptococcosis affecting the lungs, liver, lymph nodes and bones. The diagnosis was made by culture of the bone marrow. Tests of immune function showed that she was HIV-negative but the CD4 percentage was persistently low. Idiopathic CD4+ T-lymphocytopenia was diagnosed. The child died despite two courses of anti-fungal therapy.
    Matched MeSH terms: Lung/microbiology
  15. Dasgupta B, Nandalal P
    Trans R Soc Trop Med Hyg, 1974;68(2):173.
    PMID: 4460305
    Matched MeSH terms: Lung/microbiology*
  16. Sabri MY, Zamri-Saad M, Mutalib AR, Israf DA, Muniandy N
    Vet Microbiol, 2000 Apr 04;73(1):13-23.
    PMID: 10731614
    The outer membrane proteins (OMP) were extracted from the P. haemolytica A2, A7 and A9 to determine their potential as immunogens and their capability for cross-protection. Sixty lambs of approximately 9 months old were divided into four main groups. Animals in Group 1 were vaccinated with 2ml vaccine containing 100microg/ml of the outer membrane proteins of P. haemolytica A2. Animals in Group 2 were similarly vaccinated with the OMPs of P. haemolytica A7 while Group 3 with OMPs of P. haemolytica A9. Animals in Group 4 were unvaccinated control. During the course of the study, serum was collected to evaluate the antibody levels toward each OMP. There appeared to be good immune responses. However, high antibody levels did not necessarily result in good protection of the animals, particularly against cross-infection with P. haemolytica A9 in animals vaccinated with the OMPs of P. haemolytica A2. It seemed that the antibody responses were more specific toward the homologous challenge but generally did not cross-protect against heterologous serotype challenge. However, the OMPs of P. haemolytica A7 produced good in vivo cross-protection and excellent correlations when good antibody responses against all serotypes led to successful reductions of the extent of lung lesions following homologous and heterologous challenge exposures. Thus, the OMPs of P. haemolytica A7 was effective in protecting animals against homologous and heterologous infection by live P. haemolytica A2, A7 and A9.
    Matched MeSH terms: Lung/microbiology
  17. Ohno H, Ogata Y, Suguro H, Yokota S, Watanabe A, Kamei K, et al.
    Intern. Med., 2010;49(5):491-5.
    PMID: 20190491
    Histoplasmosis, caused by Histoplasma capsulatum, is an endemic mycosis in many countries of the world except for Japan. Outbreaks of histoplasmosis among Japanese people are very rare and are mainly imported by travelers. We report an outbreak of histoplasmosis among healthy Japanese people who traveled to a resort area in Southeast Asia. Three young Japanese women traveled to Langkawi island, Malaysia and stayed on the island for five days without visiting caves, a known reservoir of H. capsulatum. All three individuals developed flu-like symptoms with multiple nodule shadows on chest X rays or chest CT scans at around ten days after their return to Japan. Serum samples obtained from the three subjects were positive for anti-Histoplasma antibody and specific PCR for H. capsulatum on lung biopsy specimens and the serum from one patient was positive. The clinical course of all three patients improved without the use of anti-fungal agents and no recurrence has been confirmed. Clinical attendants should consider histoplasmosis when they see patients with flu-like symptoms with abnormal chest X-rays after visiting H. capsulatum endemic areas, especially Southeast Asia.
    Matched MeSH terms: Lung/microbiology
  18. Dahlia H, Tan LJ, Zarrahimah Z, Maria J
    Trop Biomed, 2009 Dec;26(3):341-5.
    PMID: 20237449 MyJurnal
    The isolation of Mycoplasma hyosynoviae from a piglet with severe pneumonia is described. This is the first report of M. hyosynoviae isolation in the country. The lung sample where the isolation was made was severely consolidated, suppurative and pleurisy. The pathogenicity of the M. hyosynoviae isolated has yet to be determined.
    Matched MeSH terms: Lung/microbiology*
  19. Boo YL, How KN, Pereira DS, Chin PW, Foong KK, Lim SY
    Med J Malaysia, 2017 08;72(4):246-247.
    PMID: 28889138 MyJurnal
    Pulmonary actinomycosis is a rare yet important and challenging diagnosis to make. It is commonly confused with other lung diseases, such as tuberculosis and bronchogenic carcinoma, leading to delay diagnosis or misdiagnosis. A 49-year-old man presented with a chronic cough, hemoptysis, and pleuritic chest pain. His initial imaging studies including computed tomography (CT) was suggestive of bronchogenic carcinoma. A subsequent CTguided biopsy was consistent with pulmonary actinomycosis and excluded the possibility of bronchogenic carcinoma. He was treated with antibiotic therapy and achieved remission with complete radiological resolution upon follow-up.
    Matched MeSH terms: Lung/microbiology
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