Burkholderia pseudomallei Toxins and Clinical Implications

  • Ramar Perumal Samy
  • Gautam Sethi
  • Bradley G. Stiles
  • Sok Lin Foo
  • Octavio Luiz Franco
  • Frank Arfuso
  • Lina H. K. Lim
  • P. Gopalakrishnakone
Living reference work entry

Latest version View entry history

Part of the Toxinology book series (TOXI)


Burkholderia pseudomallei is the causal agent of melioidosis. In spite of ongoing studies, the molecular mechanisms underlying toxin-induced pathogenesis of this bacterium are not clearly elucidated for this potential biological warfare pathogen. In this review, we highlight current information of B. pseudomallei toxins and their roles in pathophysiological effects in various experimental models. Several secretary proteins/lethal factors show lethal toxicity to cells in culture via filtrates of B. pseudomallei culture. These toxins are released in culture from strains isolated from soil, animals and humans. Toxins are also found in infected patients, which strongly correlate with severity of melioidosis. Melioidosis progression begins with an environmental reservoir and bacterial attachment in the host, invasion of epithelial/macrophage cells and subsequent intercellular spread. The molecular and cellular basis of pathogenesis in melioidosis will provide a better, rational understanding toward design and development of new drugs with novel mechanisms of action.


Melioidosis Soil pathogen Lethal factors Exotoxins 


  1. Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, et al. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol. 2015;4:296–307.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Afroze SR, Rahman MR, Barai L, Hossain MD, Uddin KN. Successful treatment outcome of primary melioidosis pneumonia-a case report from Bangladesh. BMC Res Notes. 2016;9(1):100.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ahmad L, Hung TL, Mat Akhir NA, Mohamed R, Nathan S, Firdaus-Raih M. Characterization of Burkholderia pseudomallei protein BPSL1375 validates the putative hemolytic activity of the COG3176 N-Acyltransferase family. BMC Microbiol. 2015;15:270.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Aktories K. Bacterial protein toxins that modify host regulatory GTPases. Nat Rev Microbiol. 2011;9:487–98.CrossRefPubMedGoogle Scholar
  5. Aquino LL, Wu JJ. Cutaneous manifestations of category A bioweapons. J Am Acad Dermatol. 2011;65(6):1213.e1–e15.CrossRefGoogle Scholar
  6. Ashida H, Kim M, Sasakawa C. Exploitation of the host ubiquitin system by human bacterial pathogens. Nat Rev Microbiol. 2014;12:399–413.CrossRefPubMedGoogle Scholar
  7. Attar N. Bacterial secretion: MIXing up T6SS effectors. Nat Rev Microbiol. 2015;13:600.Google Scholar
  8. Bast A, Krause K, Schmidt IH, Pudla M, Brakopp S, Hopf V, et al. Caspase-1-dependent and -independent cell death pathways in Burkholderia pseudomallei infection of macrophages. PLoS Pathog. 2014;10(3):e1003986.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Ben Messaoud N, Katzarova I, Lopez JM. Basic properties of the p38 signaling pathway in response to hyperosmotic shock. PLoS One. 2015;10(9):e0135249.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Benoit TJ, Blaney DD, Gee JE, Elrod MG, Hoffmaster AR, Doker TJ, Bower WA, Walker HT. Melioidosis cases and selected reports of occupational exposures to Burkholderia pseudomallei-United States, 2008–2013 (CDC). MMWR Surveillance Summaries. 2015;64(SS05):1–9.Google Scholar
  11. Bokoch GM, Diebold B, Kim JS, Gianni D. Emerging evidence for the importance of phosphorylation in the regulation of NADPH oxidases. Antioxid Redox Signal. 2009;11(10):2429–41.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Brandtzaeg P, Kierulf P, Gaustad P, Skulberg A, Bruun JN, Halvorsen S, Sorensen E. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis. 1989;159(2):195–204.CrossRefPubMedGoogle Scholar
  13. Brown L, Wolf JM, Prados-Rosales R, Casadevall A. Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi. Nat Rev Microbiol. 2015;13:620–30.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Burtnick MN, DeShazer D, Nair V, Gherardini FC, Brett PJ. Burkholderia mallei cluster 1 type VI secretion mutants exhibit growth and actin polymerization defects in RAW 264.7 murine macrophages. Infect Immun. 2010;78(1):88–99.CrossRefPubMedGoogle Scholar
  15. Butt A, Higman VA, Williams C, Crump MP, Hemsley CM, Harmer N, et al. The HicA toxin from Burkholderia pseudomallei has a role in persister cell formation. Biochem J. 2014;459(2):333–44.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Chan YY, Chua KL. The Burkholderia pseudomallei BpeAB-OprB efflux pump: expression and impact on quorum sensing and virulence. J Bacteriol. 2005;187(14):4707–19.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Chan YY, Tan TM, Ong YM, Chua KL. BpeAB-OprB, a multidrug efflux pump in Burkholderia pseudomallei. Antimicrob Agents Chemother. 2004;48(4):1128–35.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Chan YY, Bian HS, Tan TM, Mattmann ME, Geske GD, Igarashi J, Hatano T, Suga H, Blackwell HE, Chua KL. Control of quorum sensing by a Burkholderia pseudomallei multidrug efflux pump. J Bacteriol. 2007;189(11):4320–4.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Chen PS, Chen YS, Lin HH, Liu PJ, Ni WF, Hsueh PT, Liang SH, Chen C, Chen YL. Airborne transmission of melioidosis to humans from environmental aerosols contaminated with B. pseudomallei. PLoS Negl Trop Dis. 2015;9(6):e0003834.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Chirakul S, Bartpho T, Wongsurawat T, Taweechaisupapong S, Karoonutaisiri N, Talaat AM, et al. Characterization of BPSS1521 (bprD), a regulator of Burkholderia pseudomallei virulence gene expression in the mouse model. PLoS One. 2014;9(8):e104313.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Chutoam P, Charoensawan V, Wongtrakoongate P, Kum-Arth A, Buphamalai P, Tungpradabkul S. RpoS and oxidative stress conditions regulate succinyl-CoA: 3-ketoacid-coenzyme A transferase (SCOT) expression in Burkholderia pseudomallei. Microbiol Immunol. 2013;57(9):605–15.PubMedGoogle Scholar
  22. Cruz-Migoni A, Hautbergue GM, Artymiuk PJ, Baker PJ, Bokori-Brown M, Chang CT, et al. A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A. Science. 2011;334(6057):821–4.CrossRefPubMedGoogle Scholar
  23. Currie BJ. Melioidosis: an important cause of pneumonia in residents of and travelers returned from endemic regions. Eur Respir J. 2003;22(3):542–50.CrossRefPubMedGoogle Scholar
  24. Currie BJ, Fisher DA, Anstey NM, Jacups SP. Melioidosis: acute and chronic disease, relapse and re-activation. Trans R Soc Trop Med Hyg. 2000;94(3):301–4.CrossRefPubMedGoogle Scholar
  25. Daimon Y, Narita S, Akiyama Y. Activation of toxin-antitoxin system toxins suppresses lethality caused by the loss of sigmaE in Escherichia coli. J Bacteriol. 2015;197(14):2316–24.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Diep DT, Phuong NT, Hlaing MM, Srimanote P, Tungpradabkul S. Role of Burkholderia pseudomallei sigma N2 in amino acids utilization and in regulation of catalase E expression at the transcriptional level. Int J Bacteriol. 2015;2015:623967.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Dubail I, Berche P, Charbit A. Listeriolysin O as a reporter to identify constitutive and in vivo-inducible promoters in the pathogen Listeria monocytogenes. Infect Immun. 2000;68(6):3242–50.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Estes DM, Dow SW, Schweizer HP, Torres AG. Present and future therapeutic strategies for melioidosis and glanders. Expert Rev Anti Infect Ther. 2010;8(3):325–38.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Gan YH. Interaction between Burkholderia pseudomallei and the host immune response: sleeping with the enemy?. J Infect Dis. 2005;192(10):1845–50.Google Scholar
  30. Gilad J. Burkholderia mallei and Burkholderia pseudomallei: the causative micro-organisms of glanders and melioidosis. Recent Pat Antiinfect Drug Discov. 2007;2(3):233–41.CrossRefPubMedGoogle Scholar
  31. Goldberg E, Bishara J. Contemporary unconventional clinical use of co-trimoxazole. Clin Microbiol Infect. 2012;18(1):8–17.CrossRefPubMedGoogle Scholar
  32. Guillaume V, Wong KT, Looi RY, Georges-Courbot MC, Barrot L, Buckland R, Wild TF, Horvat B. Acute hendra virus infection: analysis of the pathogenesis and passive antibody protection in the hamster model. Virology. 2009;387(2):459–65.CrossRefPubMedGoogle Scholar
  33. Gurnev PA, Nestorovich EM. Channel-forming bacterial toxins in biosensing and macromolecule delivery. Toxins (Basel). 2014;6(8):2483–540.CrossRefGoogle Scholar
  34. Haase A, Janzen J, Barrett S, Currie B. Toxin production by Burkholderia pseudomallei strains and correlation with severity of melioidosis. J Med Microbiol. 1997;46(7):557–63.CrossRefPubMedGoogle Scholar
  35. Hadjifrangiskou M, Kostakioti M, Hultgren SJ. Antitoxins: therapy for stressed bacteria. Nat Chem Biol. 2011;7(6):345–7.CrossRefPubMedGoogle Scholar
  36. Han J, Lee JD, Bibbs L, Ulevitch RJ. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science. 1994;265(5173):808–11.CrossRefPubMedGoogle Scholar
  37. Hauser AR, Jain M, Bar-Meir M, McColley SA. Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev. 2001;24(1):29–70.CrossRefGoogle Scholar
  38. Hautbergue G. Characterisation of Burkholderia pseudomallei lethal factor 1 (BLF1). A breakthrough against melioidosis. Méd Sci (Paris). 2012;28(3):262–4.CrossRefGoogle Scholar
  39. Hayes F. Toxins-antitoxins: plasmid maintenance, programmed cell death, and cell cycle arrest. Science. 2003;301:1496–9.CrossRefPubMedGoogle Scholar
  40. Henkel JS, Baldwin MR, Barbieri JT. Toxins from bacteria. Experientia Suppl. 2010;100:1–29.CrossRefGoogle Scholar
  41. Hunt TA, Kooi C, Sokol PA, Valvano MA. Identification of Burkholderia cenocepacia genes required for bacterial survival in vivo. Infect Immun. 2004;72(7):4010–22.CrossRefPubMedPubMedCentralGoogle Scholar
  42. Joshi S, Platanias LC. Mnk kinase pathway: cellular functions and biological outcomes. World J Biol Chem. 2014;5(3):321–33.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Kimelman A, Levy A, Sberro H, Kidron S, Leavitt A, Amitai G, Yoder-Himes DR, Wurtzel O, Zhu Y, Rubin EM, Sorek R. A vast collection of microbial genes that are toxic to bacteria. Genome Res. 2012;22(4):802–9.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Kitt H, Lenney W, Gilchrist FJ. Two case reports of the successful eradication of new isolates of Burkholderia cepacia complex in children with cystic fibrosis. BMC Pharmacol Toxicol. 2016;17:14.CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lazar Adler NR, Govan B, Cullinane M, Harper M, Adler B, Boyce JD. The molecular and cellular basis of pathogenesis in melioidosis: how does Burkholderia pseudomallei cause disease?. FEMS Microbiol Rev. 2009;33:1079–99.Google Scholar
  46. Le Hello S, Currie BJ, Godoy D, Spratt BG, Mikulski M, Lacassin F, Garin B. Melioidosis in New Caledonia. Emerg Infect Dis. 2005;11(10):1607–9.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. Lee SW, Yi J, Joo SI, Kang YA, Yoon YS, Yim JJ, Yoo CG, Han SK, Shim YS, Kim EC, Kim YW. A case of melioidosis presenting as migrating pulmonary infiltration: the first case in Korea. J Korean Med Sci. 2005;20:139–42.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Leelarasamee A. Melioidosis in Southeast Asia. Acta Trop. 2000;74(2–3):129–32.CrossRefPubMedGoogle Scholar
  50. Lever MS, Nelson M, Stagg AJ, Beedham RJ, Simpson AJH. Experimental acute respiratory Burkholderia pseudomallei infection in BALB/c mice. Int J Exp Pathol. 2009;90(1):16–25.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Lubran MM. Bacterial toxins. Ann Clin Lab Sci. 1988;18(1):58–71.PubMedGoogle Scholar
  52. Maniam P, Nurul Aiezzah Z, Mohamed R, Embi N, Hasidah MS. Regulatory role of GSK3beta in the activation of NF-kappaB and modulation of cytokine levels in Burkholderia pseudomallei-infected PBMC isolated from streptozotocin-induced diabetic animals. Trop Biomed. 2015;32(1):36–48.PubMedGoogle Scholar
  53. Martin GS. Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes. Expert Rev Anti Infect Ther. 2012;10(6):701–6.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Martín MC, Fueyo JM, González-Hevia MA, Mendoza MC. Genetic procedures for identification of enterotoxigenic strains of Staphylococcus aureus from three food poisoning outbreaks. Int J Food Microbiol. 2004;94:279–86.CrossRefPubMedGoogle Scholar
  55. Massey S, Yeager LA, Blumentritt CA, Vijayakumar S, Sbrana E, Peterson JW, Brasel T, LeDuc JW, Endsley J, Torres AG. Comparative Burkholderia pseudomallei natural history virulence studies using an aerosol murine model of infection. Sci Rep. 2014;4:4305.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Michael H, Silverman MJO. Bacterial endotoxin in human disease. BioStrategies Consulting; Wako Chemicals USA, Inc. - LAL Division; 1998. p. 1–35.Google Scholar
  57. Mima T, Schweizer HP. The BpeAB-OprB effux pump of Burkholderia pseudomallei 1026b does not play a role in quorum sensing, virulence factor production, or extrusion of aminoglycosides but is a broad-spectrum drug effux system. Antimicrob Agents Chemother. 2010;54:3113–20. doi:10.1128/AAC.01803-09.Google Scholar
  58. Mohamed R, Nathan S, Embi N, Razak N, Ismail G. Inhibition of macromolecular synthesis in cultured macrophages by Pseudomonas pseudomallei exotoxin. Microbiol Immunol. 1989;33(10):811–20.CrossRefPubMedGoogle Scholar
  59. Morgan MP, Szakmany T, Power SG, Olaniyi P, Hall JE, Rowan K, Eberl M. Sepsis patients with first and second-hit infections show different outcomes depending on the causative organism. Front Microbiol. 2016;7:207.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Morosini MI, Quereda C, Gil H, Anda P, Núñez-Murga M, Cantón R, López-Vélez R. Melioidosis in travelers from Africa to Spain. Emerg Infect Dis. 2013;19(10):1656–9.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Nelson M, Nunez A, Ngugi SA, Sinclair A, Atkins TP. Characterization of lesion formation in marmosets following inhalational challenge with different strains of Burkholderia pseudomallei. Int J Exp Pathol. 2015;96(6):414–26.CrossRefPubMedGoogle Scholar
  62. Nikolakakis K, Amber S, Wilbur JS, Diner EJ, Aoki SK, Poole SJ, Tuanyok A, Keim PS, Peacock S, Hayes CS, Low DA. The toxin/immunity network of Burkholderia pseudomallei contact-dependent growth inhibition (CDI) systems. Mol Microbiol. 2012;84(3):516–29.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Overtoom R, Khieu V, Hem S, Cavailler P, Te V, Chan S, Lau P, Guillard B, Vong S. A first report of pulmonary melioidosis in Cambodia. Trans R Soc Trop Med Hyg. 2008;102:S21–5.CrossRefPubMedGoogle Scholar
  64. Panomket P, Wongsana P, Wanram S, Wongratanacheewin S, Bartpho T. Relapsed melioidosis model in C57BL/6 mice. J Med Assoc Thai. 2016;99 Suppl 1:S1–6.PubMedGoogle Scholar
  65. Pelerito A, Nunes A, Coelho S, Piedade C, Paixao P, Cordeiro R, Sampaio D, Vieira L, Gomes JP, Nuncio S. Burkholderia pseudomallei: first case of melioidosis in Portugal. IDCases. 2016;3:10–1.CrossRefPubMedPubMedCentralGoogle Scholar
  66. Podnecky NL, Rhodes KA, Schweizer HP. Efflux pump-mediated drug resistance in Burkholderia. Front Microbiol. 2015;6:305.CrossRefPubMedPubMedCentralGoogle Scholar
  67. Reckseidler-Zenteno SL, Moore R, Woods DE. Genetics and function of the capsules of Burkholderia pseudomallei and their potential as therapeutic targets. Mini Rev Med Chem. 2009;9(2):265–71.CrossRefPubMedGoogle Scholar
  68. Riyapa D, Buddhisa S, Korbsrisate S, Cuccui J, Wren BW, Stevens MP, Ato M, Lertmemongkolchai G. Neutrophil extracellular traps exhibit antibacterial activity against Burkholderia pseudomallei and are influenced by bacterial and host factors. Infect Immun. 2012;80(11):3921–9.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004;68(2):320–44.CrossRefPubMedPubMedCentralGoogle Scholar
  70. Saravu K, Vishwanath S, Kumar RS, Barkur AS, Varghese GK, Mukhyopadhyay C, Bairy I. Melioidosis – a case series from south India. Trans R Soc Trop Med Hyg. 2008;102 suppl 1:S18–20.CrossRefPubMedGoogle Scholar
  71. Sarovich DS, Price EP, Webb JR, Ward LM, Voutsinos MY, Tuanyok A, Mayo M, Kaestli M, Currie BJ. Variable virulence factors in Burkholderia pseudomallei (melioidosis) associated with human disease. PLoS One. 2014;9(3):e91682.CrossRefPubMedPubMedCentralGoogle Scholar
  72. Schuster CF, Bertram R. Toxin-antitoxin systems are ubiquitous and versatile modulators of prokaryotic cell fate. FEMS Microbiol Lett. 2013;340(2):73–85.CrossRefPubMedGoogle Scholar
  73. Schweizer HP. Mechanisms of antibiotic resistance in Burkholderia pseudomallei: implications for treatment of melioidosis. Future Microbiol. 2012;7(12):1389–99.CrossRefPubMedPubMedCentralGoogle Scholar
  74. Shenoy V, Kamath MP, Hegde MC, D’Souza T, Mammen SS. Melioidosis and tuberculosis: dual pathogens in a neck abscess. J Laryngol Otol. 2009;123(11):1285–7.CrossRefPubMedGoogle Scholar
  75. Silverman MH, Ostro MJ. Bacterial endotoxin in human disease. XOMA Ltd. 1999.Google Scholar
  76. Stevens MP, Wood MW, Taylor LA, Monaghan P, Hawes P, Jones PW, Wallis TS, Galyov EE. An Inv/Mxi-Spa-like type III protein secretion system in Burkholderia pseudomallei modulates intracellular behaviour of the pathogen. Mol Microbiol. 2002;46(3):649–59.CrossRefPubMedGoogle Scholar
  77. Stevens MP, Haque A, Atkins T, Hill J, Wood MW, Easton A, Nelson M, Underwood-Fowler C, Titball RW, Bancroft GJ, Galyov EE. Attenuated virulence and protective efficacy of a Burkholderia pseudomallei bsa type III secretion mutant in murine models of melioidosis. Microbiology. 2004;150(Pt 8):2669–76.CrossRefPubMedGoogle Scholar
  78. Stevens MP, Stevens JM, Jeng RL, Taylor LA, Wood MW, Hawes P, Monaghan P, Welch MD, Galyov EE. Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei. Mol Microbiol. 2005;56(1):40–53.CrossRefPubMedGoogle Scholar
  79. Stevens JM, Galyov EE, Stevens MP. Actin-dependent movement of bacterial pathogens. Nat Rev Microbiol. 2006;4(2):91–101.CrossRefPubMedGoogle Scholar
  80. Stone JK, DeShazer D, Brett PJ, Burtnick MN. Melioidosis: molecular aspects of pathogenesis. Expert Rev Anti Infect Ther. 2014;12(12):1487–99.CrossRefPubMedPubMedCentralGoogle Scholar
  81. Sulaiman H, Ponnampalavanar S, Mun KS, Italiano CM. Cervical abscesses due to co-infection with Burkholderia pseudomallei, Salmonella enterica serovar Stanley and Mycobacterium tuberculosis in a patient with diabetes mellitus. BMC Infect Dis. 2013;13:527.CrossRefPubMedPubMedCentralGoogle Scholar
  82. Sun J, Deng Z, Yan A. Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun. 2014;453(2):254–67.CrossRefPubMedGoogle Scholar
  83. Tay TF, Maheran M, Too SL, Hasidah MS, Ismail G, Embi N. Glycogen synthase kinase-3beta inhibition improved survivability of mice infected with Burkholderia pseudomallei. Trop Biomed. 2012;29(4):551–67.PubMedGoogle Scholar
  84. Truong KK, Moghaddam S, Al Saghbini S, Saatian B. Case of a lung mass due to melioidosis in Mexico. Am J Case Rep. 2015;16:272–5.CrossRefPubMedPubMedCentralGoogle Scholar
  85. Tsang TY, Lai ST. A case of thoracic empyema due to suppurative melioidosis. Hong Kong Med J. 2001;7(2):201–4.PubMedGoogle Scholar
  86. Ulett GC, Ketheesan N, Hirst RG. Cytokine gene expression in innately susceptible BALB/c mice and relatively resistant C57BL/6 mice during infection with virulent Burkholderia pseudomallei. Infect Immun. 2000;68(4):2034–42.CrossRefPubMedPubMedCentralGoogle Scholar
  87. Utaisincharoen P, Tangthawornchaikul N, Kespichayawattana W, Anuntagool N, Chaisuriya P, Sirisinha S. Kinetic studies of the production of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) in macrophages stimulated with Burkholderia pseudomallei endotoxin. Clin Exp Immunol. 2000;122(3):324–9.CrossRefPubMedPubMedCentralGoogle Scholar
  88. Waiwarawooth J, Jutiworakul K, Joraka W. Epidemiology and clinical outcome of melioidosis at Chonburi Hospital, Thailand. J Infect Dis Antimicrob Agents. 2008;25:1–11.Google Scholar
  89. Warner JM, Pelowa DB, Gal D, Rai G, Mayo M, Currie BJ, Govan B, Skerratt LF, Hirst RG. The epidemiology of melioidosis in the Balimo region of Papua New Guinea. Epidemiol Infect. 2008;136:965–71.CrossRefPubMedGoogle Scholar
  90. Whitby PW, VanWagoner TM, Taylor AA, Seale TW, Morton DJ, LiPuma JJ, Stull TL. Identification of an RTX determinant of Burkholderia cenocepacia J2315 by subtractive hybridization. J Med Microbiol. 2006;55(Pt 1):11–21.CrossRefPubMedGoogle Scholar
  91. Whitmore A, Krishnaswami CS. An account of the discovery of a hither to undescribed infective disease occurring among the population of Rangoon. Ind Med Gaz. 1912;47:262–7.Google Scholar
  92. Wiersinga WJ, Wieland CW, Dessing MC, Chantratita N, Cheng AC, Limmathurotsakul D, Chierakul W, Leendertse M, Florguin S, de Vos AF, White N, Dondorp AM, Day NP, Peacock SJ, van der Poll T. Toll-like receptor 2 impairs host defense in gram-negative sepsis caused by Burkholderia pseudomallei (Melioidosis). PLoS Med. 2007;4(7):e248.CrossRefPubMedPubMedCentralGoogle Scholar
  93. Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med. 2012;367(11):1035–44.CrossRefPubMedGoogle Scholar
  94. Willett JL, Ruhe ZC, Goulding CW, Low DA, Hayes CS. Contact-dependent growth inhibition (CDI) and CdiB/CdiA two-partner secretion proteins. J Mol Biol. 2015;427(23):3754–65.CrossRefPubMedPubMedCentralGoogle Scholar
  95. Williams NL, Morris JL, Rush CM, Ketheesan N. Plasmacytoid dendritic cell bactericidal activity against Burkholderia pseudomallei. Microbes Infect. 2015;17(4):311–6.CrossRefPubMedGoogle Scholar
  96. Woodman ME, Worth RG, Wooten RM. Capsule influences the deposition of critical complement C3 levels required for the killing of Burkholderia pseudomallei via NADPH-oxidase induction by human neutrophils. PLoS One. 2012;7(12):e52276.CrossRefPubMedPubMedCentralGoogle Scholar
  97. Wuthiekanun V, Langa S, Swaddiwudhipong W, Jedsadapanpong W, Kaengnet Y, Chierakul W, Day NP, Peacock SJ. Short report: melioidosis in Myanmar: forgotten but not gone?. Am J Trop Med Hyg. 2006;75:945–6.PubMedGoogle Scholar
  98. Yamaguchi Y, Park JH, Inouye M. Toxin-antitoxin systems in bacteria and archaea. Annu Rev Genet. 2011;45:61–79.CrossRefPubMedGoogle Scholar
  99. Yan XX, Porter CJ, Hardy SP, Steer D, Smith AI, Quinsey NS, Hughes V, Cheung JK, Keyburn AL, Kaldhusdal M, Moore RJ, Bannam TL, Whisstock JC, Rood JI. Structural and functional analysis of the pore-forming toxin NetB from Clostridium perfringens. MBio. 2013;4(1):e00019–13.CrossRefPubMedPubMedCentralGoogle Scholar
  100. Zong Z, Wang X, Deng Y, Zhou T. Misidentification of Burkholderia pseudomallei as Burkholderia cepacia by the VITEK 2 system. J Med Microbiol. 2012;61:1483–4.CrossRefPubMedGoogle Scholar
  101. Zulkiflee AB, Prepageran N, Philip R. Melioidosis: an uncommon cause of neck abscess. Am J Otolaryngol. 2008;29(1):72–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Ramar Perumal Samy
    • 1
    • 2
  • Gautam Sethi
    • 3
  • Bradley G. Stiles
    • 4
    • 9
  • Sok Lin Foo
    • 2
    • 8
  • Octavio Luiz Franco
    • 5
    • 6
  • Frank Arfuso
    • 7
  • Lina H. K. Lim
    • 2
    • 8
  • P. Gopalakrishnakone
    • 1
  1. 1.Venom and Toxin Research Programme, Department of AnatomyNational University of SingaporeSingaporeSingapore
  2. 2.Department of Physiology, NUS Immunology Programme, Centre for Life Sciences, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  3. 3.Department of Pharmacology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  4. 4.Integrated Toxicology DivisionUS Army Medical Research Institute of Infectious DiseasesFort DetrickUSA
  5. 5.Centro de Análises Proteômicas e Bioquímicas/Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, UCBBrasíliaBrazil
  6. 6.S. Inova Biotech Programa de Pós-Graduação em BiotecnologiaUniversidade Católica Dom BoscoCampo GrandeBrazil
  7. 7.School of Biomedical Sciences, Curtin Health Innovation Research InstituteCurtin UniversityPerthAustralia
  8. 8.NUS Graduate School for Integrative Sciences and EngineeringNational University of SingaporeSingaporeSingapore
  9. 9.Department of BiologyWilson CollegeChambersburgUSA

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