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Cited by 21Burkholderia infections and melioidosisBacterial Infections and VaccinesBartonella species infections research

Burkholderia pseudomallei invades the olfactory nerve and bulb after epithelial injury in mice and causes the formation of multinucleated giant glial cells in vitro

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Walkden, Heidi, Delbaz, Ali, Nazareth, Lynn, Batzloff, Michael, Shelper, Todd, Beacham, Ifor R., Chacko, Anu, Shah, Megha +4 more·2020·PLOS Neglected Tropical Diseases
DOI 10.1371/journal.pntd.0008017PMC PMC7002012
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Abstract

The infectious disease melioidosis is caused by the bacterium Burkholderia pseudomallei. Melioidosis is characterised by high mortality and morbidity and can involve the central nervous system (CNS). We have previously discovered that B. pseudomallei can infect the CNS via the olfactory and trigeminal nerves in mice. We have shown that the nerve path is dependent on mouse strain, with outbred mice showing resistance to olfactory nerve infection. Damage to the nasal epithelium by environmental factors is common, and we hypothesised that injury to the olfactory epithelium may increase the vulnerability of the olfactory nerve to microbial insult. We therefore investigated this, using outbred mice that were intranasally inoculated with B. pseudomallei, with or without methimazole-induced injury to the olfactory neuroepithelium. Methimazole-mediated injury resulted in increased B. pseudomallei invasion of the olfactory epithelium, and only in pre-injured animals were bacteria found in the olfactory nerve and bulb. In vitro assays demonstrated that B. pseudomallei readily infected glial cells isolated from the olfactory and trigeminal nerves (olfactory ensheathing cells and trigeminal Schwann cells, respectively). Bacteria were degraded by some cells but persisted in other cells, which led to the formation of multinucleated giant cells (MNGCs), with olfactory ensheathing cells less likely to form MNGCs than Schwann cells. Double Cap mutant bacteria, lacking the protein BimA, did not form MNGCs. These data suggest that injuries to the olfactory epithelium expose the primary olfactory nervous system to bacterial invasion, which can then result in CNS infection with potential pathogenic consequences for the glial cells.

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  1. [1]Parameswaran U, Baird RW, Ward LM, Currie BJ. Melioidosis at Royal Darwin Hospital in the big 2009–2010 wet season: comparison with the preceding 20 years. The Medical journal of Australia. 2012; 196(5): 345– 8. 10.5694/mja11.11170. 22432675 · DOI
  2. [2]Cheng AC, Currie BJ. Melioidosis: epidemiology, pathophysiology, and management. Clinical microbiology reviews. 2005; 18(2): 383– 416. 10.1128/CMR.18.2.383-416.2005 15831829 PMC1082802 · DOI
  3. [3]Limmathurotsakul D, Golding N, Dance DA, Messina JP, Pigott DM, Moyes CL, et al Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol. 2016; 1(1): 15008 Epub 2016/02/16. 10.1038/nmicrobiol.2015.8 27571754 · DOI
  4. [4]Chaowagul W, White NJ, Dance DA, Wattanagoon Y, Naigowit P, Davis TM, et al Melioidosis: a major cause of community-acquired septicemia in northeastern Thailand. The Journal of infectious diseases. 1989; 159(5): 890– 9. 10.1093/infdis/159.5.890. 2708842 · DOI
  5. [5]Inglis TJ, Sousa AQ. The public health implications of melioidosis. Braz J Infect Dis. 2009; 13(1): 59– 66. Epub 2009/07/07. 10.1590/s1413-86702009000100013. 19578632 · DOI
  6. [6]Jeddeloh JA, Fritz DL, Waag DM, Hartings JM, Andrews GP. Biodefense-driven murine model of pneumonic melioidosis. Infection and immunity. 2003; 71(1): 584– 7. 10.1128/IAI.71.1.584-587.2003 12496217 PMC143420 · DOI
  7. [7]Malczewski AB, Oman KM, Norton RE, Ketheesan N. Clinical presentation of melioidosis in Queensland, Australia. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2005; 99(11): 856– 60. 10.1016/j.trstmh.2005.06.015. 16111729 · DOI
  8. [8]Davis JS, Currie BJ, Fisher DA, Huffam SE, Anstey NM, Price RN, et al Prevention of opportunistic infections in immunosuppressed patients in the tropical top end of the Northern Territory. Communicable diseases intelligence quarterly report. 2003; 27(4): 526– 32.. 15508512
  9. [9]Deuble M, Aquilina C, Norton R. Neurologic melioidosis. The American journal of tropical medicine and hygiene. 2013; 89(3): 535– 9. 10.4269/ajtmh.12-0559 23836574 PMC3771296 · DOI
  10. [10]Currie BJ, Fisher DA, Howard DM, Burrow JN. Neurological melioidosis. Acta tropica. 2000; 74(2–3): 145– 51. 10.1016/s0001-706x(99)00064-9. 10674643 · DOI
  11. [11]Saravu K, Kadavigere R, Shastry AB, Pai R, Mukhopadhyay C. Neurologic melioidosis presented as encephalomyelitis and subdural collection in two male labourers in India. J Infect Dev Ctries. 2015; 9(11): 1289– 93. Epub 2015/12/02. 10.3855/jidc.6586. 26623640 · DOI
  12. [12]Wongwandee M, Linasmita P. Central nervous system melioidosis: A systematic review of individual participant data of case reports and case series. PLoS Negl Trop Dis. 2019; 13(4): e0007320 Epub 2019/04/26. 10.1371/journal.pntd.0007320 31022232 PMC6504113 · DOI
  13. [13]Hsu CC, Singh D, Kwan G, Deuble M, Aquilina C, Korah I, et al Neuromelioidosis: Craniospinal MRI Findings in Burkholderia pseudomallei Infection. J Neuroimaging. 2016; 26(1): 75– 82. Epub 2015/08/11. 10.1111/jon.12282. 26256582 · DOI
  14. [14]Dando SJ, Ipe DS, Batzloff M, Sullivan MJ, Crossman DK, Crowley M, et al Burkholderia pseudomallei Capsule Exacerbates Respiratory Melioidosis but Does Not Afford Protection against Antimicrobial Signaling or Bacterial Killing in Human Olfactory Ensheathing Cells. Infection and immunity. 2016; 84(7): 1941– 56. Epub 2016/04/20. 10.1128/IAI.01546-15 27091931 PMC4936350 · DOI
  15. [15]Nazareth L, Chen M, Shelper T, Shah M, Tello Velasquez J, Walkden H, et al Novel insights into the glia limitans of the olfactory nervous system. The Journal of comparative neurology. 2018 Epub 2018/12/29. 10.1002/cne.24618. 30592044 · DOI · Paper page
  16. [16]Owen SJ, Batzloff M, Chehrehasa F, Meedeniya A, Casart Y, Logue CA, et al Nasal-associated lymphoid tissue and olfactory epithelium as portals of entry for Burkholderia pseudomallei in murine melioidosis. The Journal of infectious diseases. 2009; 199(12): 1761– 70. 10.1086/599210. 19456230 · DOI
  17. [17]St John JA, Ekberg JA, Dando SJ, Meedeniya AC, Horton RE, Batzloff M, et al Burkholderia pseudomallei penetrates the brain via destruction of the olfactory and trigeminal nerves: implications for the pathogenesis of neurological melioidosis. mBio. 2014; 5(2): e00025 10.1128/mBio.00025-14 24736221 PMC3993850 · DOI
  18. [18]St John JA, Walkden H, Nazareth L, Beagley KW, Ulett GC, Batzloff MR, et al Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation. Infection and immunity. 2016; 84(9): 2681– 8. 10.1128/IAI.00361-16 27382023 PMC4995904 · DOI
  19. [19]Hoppe I, Brenneke B, Rohde M, Kreft A, Haussler S, Reganzerowski A, et al Characterization of a murine model of melioidosis: comparison of different strains of mice. Infection and immunity. 1999; 67(6): 2891– 900. Epub 1999/05/25. 10338496 PMC96597
  20. [20]Leakey AK, Ulett GC, Hirst RG. BALB/c and C57Bl/6 mice infected with virulent Burkholderia pseudomallei provide contrasting animal models for the acute and chronic forms of human melioidosis. Microb Pathog. 1998; 24(5): 269– 75. Epub 1998/06/13. 10.1006/mpat.1997.0179. 9600859 · DOI
  21. [21]Graziadei PP, Graziadei GA. Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons. J Neurocytol. 1979; 8(1): 1– 18. 10.1007/bf01206454. 438867 · DOI
  22. [22]Graziadei PP, Monti Graziadei GA. Neurogenesis and neuron regeneration in the olfactory system of mammals. III. Deafferentation and reinnervation of the olfactory bulb following section of the fila olfactoria in rat. J Neurocytol. 1980; 9(2): 145– 62. 10.1007/bf01205155. 7441292 · DOI
  23. [23]Graziadei PP, Monti Graziadei GA. Neurogenesis and plasticity of the olfactory sensory neurons. Ann N Y Acad Sci. 1985; 457: 127– 42. 10.1111/j.1749-6632.1985.tb20802.x. 3913359 · DOI
  24. [24]Doty RL, Mishra A. Olfaction and its alteration by nasal obstruction, rhinitis, and rhinosinusitis. Laryngoscope. 2001; 111(3): 409– 23. Epub 2001/02/27. 10.1097/00005537-200103000-00008. 11224769 PMC7165948 · DOI
  25. [25]Knight A. Anosmia. Lancet. 1988; 2(8609): 512 Epub 1988/08/27. 10.1016/s0140-6736(88)90160-2. 2900434 · DOI
  26. [26]Menick FJ, Salibian A. Primary intranasal lining injury cause, deformities, and treatment plan. Plast Reconstr Surg. 2014; 134(5): 1045– 56. Epub 2014/10/28. 10.1097/PRS.0000000000000694. 25347637 · DOI · Paper page
  27. [27]Nordin S, Bramerson A. Complaints of olfactory disorders: epidemiology, assessment and clinical implications. Curr Opin Allergy Clin Immunol. 2008; 8(1): 10– 5. Epub 2008/01/12. 10.1097/ACI.0b013e3282f3f473. 18188011 · DOI
  28. [28]Seo BS, Lee HJ, Mo JH, Lee CH, Rhee CS, Kim JW. Treatment of postviral olfactory loss with glucocorticoids, Ginkgo biloba, and mometasone nasal spray. Arch Otolaryngol Head Neck Surg. 2009; 135(10): 1000– 4. Epub 2009/10/21. 10.1001/archoto.2009.141. 19841338 · DOI
  29. [29]Watanabe K, Kiuna C. Epithelial damage of nasal mucosa in nasal allergy. Ann Otol Rhinol Laryngol. 1998; 107(7): 564– 70. Epub 1998/07/31. 10.1177/000348949810700704. 9682850 · DOI
  30. [30]Li Y, Field PM, Raisman G. Olfactory ensheathing cells and olfactory nerve fibroblasts maintain continuous open channels for regrowth of olfactory nerve fibres. Glia. 2005; 52(3): 245– 51. 10.1002/glia.20241. 15968636 · DOI
  31. [31]Chehrehasa F, Ekberg JA, Lineburg K, Amaya D, Mackay-Sim A, St John JA. Two phases of replacement replenish the olfactory ensheathing cell population after injury in postnatal mice. Glia. 2012; 60(2): 322– 32. Epub 2011/11/09. 10.1002/glia.22267. 22065423 · DOI
  32. [32]Brittebo EB. Metabolism-dependent toxicity of methimazole in the olfactory nasal mucosa. Pharmacology & toxicology. 1995; 76(1): 76– 9. Epub 1995/01/01. 10.1111/j.1600-0773.1995.tb00107.x. 7753763 · DOI · Paper page
  33. [33]Chehrehasa F, Windus LCE, Ekberg JAK, Scott SE, Amaya D, Mackay-Sim A, et al Olfactory glia enhance neonatal axon regeneration. Molecular and Cellular Neuroscience. 2010; 45(3): 277– 88. 10.1016/j.mcn.2010.07.002 20621189 · DOI
  34. [34]Nazareth L, Lineburg KE, Chuah MI, Tello Velasquez J, Chehrehasa F, St John JA, et al Olfactory ensheathing cells are the main phagocytic cells that remove axon debris during early development of the olfactory system. The Journal of comparative neurology. 2015; 523(3): 479– 94. 10.1002/cne.23694. 25312022 · DOI · Paper page
  35. [35]Beecher K, Hafner LM, Ekberg J, St John JA, Chehrehasa F. Combined VEGF/PDGF improves olfactory regeneration after unilateral bulbectomy in mice. Neural Regen Res. 2018; 13(10): 1820– 6. Epub 2018/08/24. 10.4103/1673-5374.238713 30136698 PMC6128065 · DOI
  36. [36]Chehrehasa F, Ekberg JA, St John JA. A novel method using intranasal delivery of EdU demonstrates that accessory olfactory ensheathing cells respond to injury by proliferation. Neuroscience letters. 2014; 563: 90– 5. Epub 2014/02/04. 10.1016/j.neulet.2014.01.043. 24486842 · DOI
  37. [37]Horton RE, Grant GD, Matthews B, Batzloff M, Owen SJ, Kyan S, et al Quorum sensing negatively regulates multinucleate cell formation during intracellular growth of Burkholderia pseudomallei in macrophage-like cells. PloS one. 2013; 8(5): e63394 Epub 2013/05/25. 10.1371/journal.pone.0063394 23704903 PMC3660431 · DOI
  38. [38]Windus LCE, Claxton C, Allen CL, Key B, St John JA. Motile membrane protrusions regulate cell–cell adhesion and migration of olfactory ensheathing glia. Glia. 2007; 55(16): 1708– 19. 10.1002/glia.20586 17893920 · DOI
  39. [39]Boddey JA, Day CJ, Flegg CP, Ulrich RL, Stephens SR, Beacham IR, et al The bacterial gene lfpA influences the potent induction of calcitonin receptor and osteoclast-related genes in Burkholderia pseudomallei-induced TRAP-positive multinucleated giant cells. Cellular microbiology. 2007; 9(2): 514– 31. Epub 2006/09/22. 10.1111/j.1462-5822.2006.00807.x. 16987331 · DOI
  40. [40]Panni P, Ferguson IA, Beacham I, Mackay-Sim A, Ekberg JA, St John JA. Phagocytosis of bacteria by olfactory ensheathing cells and Schwann cells. Neuroscience letters. 2013; 539: 65– 70. Epub 2013/02/19. 10.1016/j.neulet.2013.01.052. 23415759 · DOI
  41. [41]Windus LC, Claxton C, Allen CL, Key B, St John JA. Motile membrane protrusions regulate cell-cell adhesion and migration of olfactory ensheathing glia. Glia. 2007; 55(16): 1708– 19. Epub 2007/09/26. 10.1002/glia.20586. 17893920 · DOI
  42. [42]Nazareth L, Tello Velasquez J, Lineburg KE, Chehrehasa F, St John JA, Ekberg JA. Differing phagocytic capacities of accessory and main olfactory ensheathing cells and the implication for olfactory glia transplantation therapies. Mol Cell Neurosci. 2015; 65: 92– 101. 10.1016/j.mcn.2015.03.005. 25752729 · DOI · Paper page
  43. [43]Ekberg JA, Amaya D, Chehrehasa F, Lineburg K, Claxton C, Windus LC, et al OMP-ZsGreen fluorescent protein transgenic mice for visualisation of olfactory sensory neurons in vivo and in vitro. J Neurosci Methods. 2011; 196(1): 88– 98. Epub 2011/01/18. 10.1016/j.jneumeth.2011.01.008. 21236301 · DOI
  44. [44]Xie F, Zhou X, Genter MB, Behr M, Gu J, Ding X. The tissue-specific toxicity of methimazole in the mouse olfactory mucosa is partly mediated through target-tissue metabolic activation by CYP2A5. Drug metabolism and disposition: the biological fate of chemicals. 2011; 39(6): 947– 51. 10.1124/dmd.110.037895. 21415250 PMC3100904 · DOI · Paper page
  45. [45]Harley VS, Dance DA, Tovey G, Drasar BS. Interaction of Pseudomonas pseudomallei with macrophages. Biochem Soc Trans. 1994; 22(2): 88S Epub 1994/05/01. 10.1042/bst022088s. 7525379 · DOI
  46. [46]Krakauer T. Living dangerously: Burkholderia pseudomallei modulates phagocyte cell death to survive. Med Hypotheses. 2018; 121: 64– 9. Epub 2018/11/07. 10.1016/j.mehy.2018.09.028. 30396496 · DOI
  47. [47]Pruksachartvuthi S, Aswapokee N, Thankerngpol K. Survival of Pseudomonas pseudomallei in human phagocytes. J Med Microbiol. 1990; 31(2): 109– 14. Epub 1990/02/01. 10.1099/00222615-31-2-109. 2304065 · DOI
  48. [48]Kespichayawattana W, Rattanachetkul S, Wanun T, Utaisincharoen P, Sirisinha S. Burkholderia pseudomallei Induces Cell Fusion and Actin-Associated Membrane Protrusion: a Possible Mechanism for Cell-to-Cell Spreading. Infection and immunity. 2000; 68(9): 5377– 84. 10.1128/iai.68.9.5377-5384.2000 10948167 PMC101801 · DOI
  49. [49]Brooks PJ, Glogauer M, McCulloch CA. An Overview of the Derivation and Function of Multinucleated Giant Cells and Their Role in Pathologic Processes. Am J Pathol. 2019; 189(6): 1145– 58. Epub 2019/03/31. 10.1016/j.ajpath.2019.02.006. 30926333 · DOI
  50. [50]Leskovar A, Turek J, Borgens RB. Giant multinucleated macrophages occur in acute spinal cord injury. Cell Tissue Res. 2001; 304(2): 311– 5. Epub 2001/06/09. 10.1007/s004410000325. 11396724 · DOI
  51. [51]Milde R, Ritter J, Tennent GA, Loesch A, Martinez FO, Gordon S, et al Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction. Cell Rep. 2015; 13(9): 1937– 48. Epub 2015/12/03. 10.1016/j.celrep.2015.10.065 26628365 PMC4675895 · DOI
  52. [52]Benanti EL, Nguyen CM, Welch MD. Virulent Burkholderia species mimic host actin polymerases to drive actin-based motility. Cell. 2015; 161(2): 348– 60. 10.1016/j.cell.2015.02.044 25860613 PMC4393530 · DOI
  53. [53]Macedo-Ramos H, Ruiz-Mendoza S, Mariante RM, Guimarães EV, Quadros-de-Souza LC, Paiva MM, et al Streptococcus pneumoniae resists intracellular killing by olfactory ensheathing cells but not by microglia. Scientific Reports. 2016; 6: 36813 10.1038/srep36813 PMC5101813. 27827453 PMC5101813 · DOI
  54. [54]Tacchi L, Musharrafieh R, Larragoite ET, Crossey K, Erhardt EB, Martin SAM, et al Nasal immunity is an ancient arm of the mucosal immune system of vertebrates. Nat Commun. 2014; 5: 5205 Epub 2014/10/23. 10.1038/ncomms6205 25335508 PMC4321879 · DOI
  55. [55]Wu HY, Russell MW. Nasal lymphoid tissue, intranasal immunization, and compartmentalization of the common mucosal immune system. Immunol Res. 1997; 16(2): 187– 201. Epub 1997/01/01. 10.1007/bf02786362. 9212364 · DOI · Paper page
  56. [56]Yoshida SH, Gershwin ME. Immunity, infection, and nasal disease. Clin Rev Allergy Immunol. 1998; 16(1–2): 3– 24. Epub 1998/04/30. 10.1007/BF02739326. 9561335 · DOI
  57. [57]Bearoff F, Del Rio R, Case LK, Dragon JA, Nguyen-Vu T, Lin CY, et al Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity. Genes Immun. 2016; 17(7): 386– 95. Epub 2016/09/23. 10.1038/gene.2016.37 27653816 PMC5133152 · DOI
  58. [58]Chia R, Achilli F, Festing MF, Fisher EM. The origins and uses of mouse outbred stocks. Nat Genet. 2005; 37(11): 1181– 6. Epub 2005/10/29. 10.1038/ng1665. 16254564 · DOI
  59. [59]Harrison DE, Astle CM, Niazi MKK, Major S, Beamer GL. Genetically diverse mice are novel and valuable models of age-associated susceptibility to Mycobacterium tuberculosis. Immun Ageing. 2014; 11(1): 24 Epub 2015/01/22. 10.1186/s12979-014-0024-6 25606048 PMC4299371 · DOI
  60. [60]Jonker MA, Hermsen JL, Gomez FE, Sano Y, Kudsk KA. Injury induces localized airway increases in pro-inflammatory cytokines in humans and mice. Surg Infect (Larchmt). 2011; 12(1): 49– 56. Epub 2010/12/21. 10.1089/sur.2010.040 21166596 PMC3064869 · DOI
  61. [61]Lutz CM, Linder CC, Davidson MT. Strains, Stocks and Mutant Mice In: Hedrich HJ, editor. The Laboratory Mouse. 2nd ed: Academic Press; 2012 p. 37– 56.
  62. [62]Niazi MK, Dhulekar N, Schmidt D, Major S, Cooper R, Abeijon C, et al Lung necrosis and neutrophils reflect common pathways of susceptibility to Mycobacterium tuberculosis in genetically diverse, immune-competent mice. Dis Model Mech. 2015; 8(9): 1141– 53. Epub 2015/07/25. 10.1242/dmm.020867 26204894 PMC4582107 · DOI
  63. [63]Poltorak A, Apalko S, Sherbak S. Wild-derived mice: from genetic diversity to variation in immune responses. Mamm Genome. 2018; 29(7–8): 577– 84. Epub 2018/07/30. 10.1007/s00335-018-9766-3. 30056578 PMC12022659 · DOI
  64. [64]Sunagar R, Kumar S, Namjoshi P, Rosa SJ, Hazlett KRO, Gosselin EJ. Evaluation of an outbred mouse model for Francisella tularensis vaccine development and testing. PloS one. 2018; 13(12): e0207587 Epub 2018/12/12. 10.1371/journal.pone.0207587 30533047 PMC6289435 · DOI
  65. [65]Tuttle AH, Philip VM, Chesler EJ, Mogil JS. Comparing phenotypic variation between inbred and outbred mice. Nat Methods. 2018; 15(12): 994– 6. Epub 2018/12/07. 10.1038/s41592-018-0224-7. 30504873 PMC6518396 · DOI · Paper page
  66. [66]Herbert RP, Harris J, Chong KP, Chapman J, West AK, Chuah MI. Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway. Journal of neuroinflammation. 2012; 9: 109 10.1186/1742-2094-9-109 22642871 PMC3411416 · DOI · Paper page
  67. [67]Crowell J, Wiley JA, Bessen RA. Lesion of the olfactory epithelium accelerates prion neuroinvasion and disease onset when prion replication is restricted to neurons. PloS one. 2015; 10(3): e0119863 Epub 2015/03/31. 10.1371/journal.pone.0119863 25822718 PMC4379011 · DOI
  68. [68]Upadhyay UD, Holbrook EH. Olfactory loss as a result of toxic exposure. Otolaryngol Clin North Am. 2004; 37(6): 1185– 207. Epub 2004/11/27. 10.1016/j.otc.2004.05.003. 15563910 · DOI
  69. [69]Genter MB, Deamer NJ, Blake BL, Wesley DS, Levi PE. Olfactory toxicity of methimazole: dose-response and structure-activity studies and characterization of flavin-containing monooxygenase activity in the Long-Evans rat olfactory mucosa. Toxicol Pathol. 1995; 23(4): 477– 86. Epub 1995/07/01. 10.1177/019262339502300404. 7501959 · DOI
  70. [70]Sakamoto T, Kondo K, Kashio A, Suzukawa K, Yamasoba T. Methimazole-induced cell death in rat olfactory receptor neurons occurs via apoptosis triggered through mitochondrial cytochrome c-mediated caspase-3 activation pathway. J Neurosci Res. 2007; 85(3): 548– 57. Epub 2006/12/16. 10.1002/jnr.21155. 17171702 · DOI
  71. [71]Cooper DS. The side effects of antithyroid drugs. Endocrinologist. 1999; 9(6): 457– 67.
  72. [72]Hallman BL, Hurst JW. Loss of taste as toxic effect of methimazole (tapazole) therapy; report of three cases. J Am Med Assoc. 1953; 152(4): 322 Epub 1953/05/23. 10.1001/jama.1953.63690040006007d. 13044528 · DOI
  73. [73]Schiffman SS, Gatlin CA. Clinical physiology of taste and smell. Annu Rev Nutr. 1993; 13: 405– 36. Epub 1993/01/01. 10.1146/annurev.nu.13.070193.002201. 8369152 · DOI
  74. [74]Clayton AJ, Lisella RS, Martin DG. Melioidosis: a serological survey in military personnel. Mil Med. 1973; 138(1): 24– 6. Epub 1973/01/01.. 4630052
  75. [75]Currie BJ. Melioidosis: evolving concepts in epidemiology, pathogenesis, and treatment. Seminars in respiratory and critical care medicine. 2015; 36(1): 111– 25. Epub 2015/02/03. 10.1055/s-0034-1398389. 25643275 · DOI
  76. [76]Chadwick DR, Ang B, Sitoh YY, Lee CC. Cerebral melioidosis in Singapore: a review of five cases. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2002; 96(1): 72– 6. Epub 2002/04/03. 10.1016/s0035-9203(02)90248-8. 11926000 · DOI
  77. [77]Doty RL, Riklan M, Deems DA, Reynolds C, Stellar S. The olfactory and cognitive deficits of Parkinson's disease: evidence for independence. Annals of neurology. 1989; 25(2): 166– 71. 10.1002/ana.410250210. 2919866 · DOI
  78. [78]Doty RL, Stern MB, Pfeiffer C, Gollomp SM, Hurtig HI. Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson's disease. Journal of neurology, neurosurgery, and psychiatry. 1992; 55(2): 138– 42. 10.1136/jnnp.55.2.138 1538221 PMC488979 · DOI
  79. [79]Mesholam RI, Moberg PJ, Mahr RN, Doty RL. Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer's and Parkinson's diseases. Archives of neurology. 1998; 55(1): 84– 90. 10.1001/archneur.55.1.84. 9443714 · DOI · Paper page
  80. [80]Kurtz P, Schuurman T, Prinz H. Loss of smell leads to dementia in mice: is Alzheimer's disease a degenerative disorder of the olfactory system? Journal of protein chemistry. 1989; 8(3): 448– 51. 10.1007/bf01674321. 2789687 · DOI
  81. [81]Nordin S, Monsch AU, Murphy C. Unawareness of smell loss in normal aging and Alzheimer's disease: discrepancy between self-reported and diagnosed smell sensitivity. The journals of gerontology Series B, Psychological sciences and social sciences. 1995; 50(4): P187– 92. 10.1093/geronb/50b.4.p187. 7606530 · DOI
  82. [82]Velayudhan L, Pritchard M, Powell JF, Proitsi P, Lovestone S. Smell identification function as a severity and progression marker in Alzheimer's disease. International psychogeriatrics. 2013; 25(7): 1157– 66. 10.1017/S1041610213000446. 23597130 · DOI
  83. [83]Haehner A, Hummel T, Reichmann H. Olfactory loss in Parkinson's disease. Parkinson's disease. 2011; 2011: 450939 10.4061/2011/450939 21687752 PMC3109349 · DOI
  84. [84]Pentzek M, Grass-Kapanke B, Ihl R. Odor identification in Alzheimer's disease and depression. Aging clinical and experimental research. 2007; 19(3): 255– 8. 10.1007/bf03324698. 17607095 · DOI
  85. [85]Kovacs I, Torok I, Zombori J, Kasa P. Neuropathologic changes in the olfactory bulb in Alzheimer's disease. Neurobiology. 1996; 4(1–2): 123– 6.. 9116690
  86. [86]Kovacs T, Cairns NJ, Lantos PL. beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer's disease. Neuropathology and applied neurobiology. 1999; 25(6): 481– 91. 10.1046/j.1365-2990.1999.00208.x. 10632898 · DOI
  87. [87]Ohm TG, Braak H. Olfactory bulb changes in Alzheimer's disease. Acta neuropathologica. 1987; 73(4): 365– 9. 10.1007/bf00688261. 3618129 · DOI
  88. [88]Struble RG, Clark HB. Olfactory bulb lesions in Alzheimer's disease. Neurobiology of aging. 1992; 13(4): 469– 73. 10.1016/0197-4580(92)90074-8. 1508297 · DOI
  89. [89]Thomann PA, Dos Santos V, Toro P, Schonknecht P, Essig M, Schroder J. Reduced olfactory bulb and tract volume in early Alzheimer's disease—a MRI study. Neurobiology of aging. 2009; 30(5): 838– 41. 10.1016/j.neurobiolaging.2007.08.001. 17875348 · DOI
  90. [91]Beach TG, White CL 3rd, Hladik CL, Sabbagh MN, Connor DJ, Shill HA, et al Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders. Acta neuropathologica. 2009; 117(2): 169– 74. 10.1007/s00401-008-0450-7 18982334 PMC2631085 · DOI
  91. [92]Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiology of aging. 2003; 24(2): 197– 211. 10.1016/s0197-4580(02)00065-9. 12498954 · DOI · Paper page
  92. [93]Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004; 318(1): 121– 34. 10.1007/s00441-004-0956-9. 15338272 · DOI · Paper page
  93. [94]Zapiec B, Dieriks BV, Tan S, Faull RLM, Mombaerts P, Curtis MA. A ventral glomerular deficit in Parkinson's disease revealed by whole olfactory bulb reconstruction. Brain: a journal of neurology. 2017; 140(10): 2722– 36. 10.1093/brain/awx208 28969383 PMC5841151 · DOI
  94. [95]Hasegawa-Ishii S, Shimada A, Imamura F. Lipopolysaccharide-initiated persistent rhinitis causes gliosis and synaptic loss in the olfactory bulb. Sci Rep. 2017; 7(1): 11605 10.1038/s41598-017-10229-w 28912588 PMC5599676 · DOI
  95. [96]Doty RL. The olfactory vector hypothesis of neurodegenerative disease: is it viable? Annals of neurology. 2008; 63(1): 7– 15. 10.1002/ana.21327. 18232016 · DOI
  96. [97]Block ML, Calderon-Garciduenas L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. 2009; 32(9): 506– 16. Epub 2009/09/01. 10.1016/j.tins.2009.05.009 19716187 PMC2743793 · DOI
  97. [98]Arking EJ, Appelt DM, Abrams JT, Kolbe S, Hudson AP, Balin BJ. Ultrastructural Analysis of Chlamydia Pneumoniae in the Alzheimer's Brain. Pathogenesis: the journal of mechanisms in disease processes. 1999; 1(3): 201– 11. 20671799 PMC2910921
  98. [99]Balin BJ, Gerard HC, Arking EJ, Appelt DM, Branigan PJ, Abrams JT, et al Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain. Medical microbiology and immunology. 1998; 187(1): 23– 42. 10.1007/s004300050071. 9749980 · DOI · Paper page
  99. [100]Gerard HC, Dreses-Werringloer U, Wildt KS, Deka S, Oszust C, Balin BJ, et al Chlamydophila (Chlamydia) pneumoniae in the Alzheimer's brain. FEMS immunology and medical microbiology. 2006; 48(3): 355– 66. 10.1111/j.1574-695X.2006.00154.x. 17052268 · DOI · Paper page
  100. [101]Gerard HC, Wildt KL, Whittum-Hudson JA, Lai Z, Ager J, Hudson AP. The load of Chlamydia pneumoniae in the Alzheimer's brain varies with APOE genotype. Microb Pathog. 2005; 39(1–2): 19– 26. 10.1016/j.micpath.2005.05.002. 15998578 · DOI
  101. [103]Little CS, Joyce TA, Hammond CJ, Matta H, Cahn D, Appelt DM, et al Detection of bacterial antigens and Alzheimer's disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae. Frontiers in aging neuroscience. 2014; 6: 304 10.3389/fnagi.2014.00304 25538615 PMC4257355 · DOI · Paper page
  102. [104]Shima K, Kuhlenbaumer G, Rupp J. Chlamydia pneumoniae infection and Alzheimer's disease: a connection to remember? Medical microbiology and immunology. 2010; 199(4): 283– 9. Epub 2010/05/07. 10.1007/s00430-010-0162-1. 20445987 · DOI
  103. [105]Liu B, Gao HM, Hong JS. Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation. Environmental health perspectives. 2003; 111(8): 1065– 73. Epub 2003/06/27. 10.1289/ehp.6361 12826478 PMC1241555 · DOI
  104. [107]Balin BJ, Hammond CJ, Little CS, Hingley ST, Al-Atrache Z, Appelt DM, et al Chlamydia pneumoniae: An Etiologic Agent for Late-Onset Dementia. Frontiers in aging neuroscience. 2018; 10: 302 10.3389/fnagi.2018.00302 30356749 PMC6189393 · DOI · Paper page
  105. [108]Caggiu E, Arru G, Hosseini S, Niegowska M, Sechi G, Zarbo IR, et al Inflammation, Infectious Triggers, and Parkinson's Disease. Frontiers in neurology. 2019; 10: 122 10.3389/fneur.2019.00122 30837941 PMC6389614 · DOI
  106. [109]Ng CS, Azmin S, Law ZK, Sahathevan R, Wan Yahya WN, Remli R, et al An unusual neurological complication from a garden-variety organism: post-melioidosis parkinsonism. The Medical journal of Australia. 2015; 202(6): 333– 4. Epub 2015/04/04. 10.5694/mja14.00229. 25832163 · DOI
  107. [110]Dando SJ, Mackay-Sim A, Norton R, Currie BJ, St John JA, Ekberg JA, et al Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Clinical microbiology reviews. 2014; 27(4): 691– 726. Epub 2014/10/04. 10.1128/CMR.00118-13 25278572 PMC4187632 · DOI · Paper page
  108. [111]Vincent AJ, Choi-Lundberg DL, Harris JA, West AK, Chuah MI. Bacteria and PAMPs activate nuclear factor κB and Gro production in a subset of olfactory ensheathing cells and astrocytes but not in Schwann cells. Glia. 2007; 55(9): 905– 16. 10.1002/glia.20512 17427933 · DOI · Paper page
  109. [112]Möller J, Lühmann T, Chabria M, Hall H, Vogel V. Macrophages lift off surface-bound bacteria using a filopodium-lamellipodium hook-and-shovel mechanism. Scientific Reports. 2013; 3: 2884 10.1038/srep02884 https://www.nature.com/articles/srep02884#supplementary-information. 24097079 PMC3791455 · DOI
  110. [113]Stevens JM, Ulrich RL, Taylor LA, Wood MW, Deshazer D, Stevens MP, et al Actin-binding proteins from Burkholderia mallei and Burkholderia thailandensis can functionally compensate for the actin-based motility defect of a Burkholderia pseudomallei bimA mutant. Journal of bacteriology. 2005; 187(22): 7857– 62. 10.1128/JB.187.22.7857-7862.2005 16267310 PMC1280302 · DOI
  111. [114]Stevens MP, Stevens JM, Jeng RL, Taylor LA, Wood MW, Hawes P, et al Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei. Mol Microbiol. 2005; 56(1): 40– 53. Epub 2005/03/19. 10.1111/j.1365-2958.2004.04528.x. 15773977 · DOI
  112. [115]Whiteley L, Meffert T, Haug M, Weidenmaier C, Hopf V, Bitschar K, et al Entry, Intracellular Survival, and Multinucleated-Giant-Cell-Forming Activity of Burkholderia pseudomallei in Human Primary Phagocytic and Nonphagocytic Cells. Infection and immunity. 2017; 85(10): e00468– 17. 10.1128/IAI.00468-17. 28760929 PMC5607410 · DOI
  113. [116]Barton MJ, John JS, Clarke M, Wright A, Ekberg J. The Glia Response after Peripheral Nerve Injury: A Comparison between Schwann Cells and Olfactory Ensheathing Cells and Their Uses for Neural Regenerative Therapies. International journal of molecular sciences. 2017; 18(2). 10.3390/ijms18020287 28146061 PMC5343823 · DOI
  114. [117]Hess S, Rambukkana A. Cell Biology of Intracellular Adaptation of Mycobacterium leprae in the Peripheral Nervous System. Microbiology spectrum. 2019; 7(4). 10.1128/microbiolspec.BAI-0020-2019 31322104 PMC6700727 · DOI

Cited by

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Authors
Walkden, H., Delbaz, A., Nazareth, L., Batzloff, M., Shelper, T., Beacham, I. R., Chacko, A., Shah, M., Beagley, K. W., Tello Velasquez, J., St John, J. A., & Ekberg, J. A. K.
Affiliations
  • Griffith University (AU)
  • Queensland University of Technology (AU)
Corresponding author
Ekberg, Jenny A. K.
ORCID
Venue
PLOS Neglected Tropical Diseases
Publisher
Public Library of Science (PLoS)
Published
2020-01-24
Volume
14
Issue
1
Pages
e0008017
ISSN
  • 1935-2727 (ISSN-L)
  • 1935-2735
DOI
10.1371/journal.pntd.0008017
PMC
PMC7002012
OpenAlex
W3001329897
Cited by
21
References
3
Citations by year
2026: 4 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 1
FWCI
2.10
Type
journal article
Language
en
Update notices
new_version (2020-02-05)
Open access
Licence
Locations
  • PLoS neglected tropical diseases (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by)
  • Griffith Research Online (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Australian Research Council (DP150104495)
  • Clem Jones Foundation (.)
  • Menzies Health Institute Queensland (.)
  • Goda Foundation (.)
  • Australian Government Research Training Program (.)
  • Griffith University International Postgraduate Research Scholarship (.)
Topics
  • Health Sciences › Medicine › Epidemiology › Burkholderia infections and melioidosis
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
  • Life Sciences › Immunology and Microbiology › Parasitology › Bartonella species infections research
Keywords
Burkholderia pseudomallei, melioidosis, olfactory nerve, olfactory bulb, olfactory ensheathing cells, multinucleated giant cells, central nervous system infection, Bima
MeSH terms
Animals, Humans, Melioidosis, Methimazole, Mice, Transgenic, Olfactory Bulb, Olfactory Nerve, Antithyroid Agents, Giant Cells, Burkholderia pseudomallei, Genes, Reporter, Respiratory Mucosa, Mice, S100 Calcium Binding Protein beta Subunit

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