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Distinct Pathogenic Patterns of Burkholderia pseudomallei Isolates Selected from Caenorhabditis elegans and Dictyostelium discoideum Models

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  • 1 Department of Biotechnology, National Kaohsiung Normal University, Kaohsiung, Taiwan;
  • | 2 Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;
  • | 3 Medical Research Department, General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan;
  • | 4 School of Medicine, Institute of Public Health, National Yang-Ming University, Taipei, Taiwan;
  • | 5 Department of Internal Medicine, National Yang-Ming University, Taipei, Taiwan

Burkholderia pseudomallei is a selective agent that causes septic melioidosis and exhibits a broad range of lethal doses in animals. Host cellular virulence and phagocytic resistance are pathologic keys of B. pseudomallei. We first proposed Caenorhabditis elegans as the host cellular virulence model to mimic bacterial virulence against mammals and second established the resistance of B. pseudomallei to predation by Dictyostelium discoideum as the phagocytosis model. The saprophytic sepsis–causing Burkholderia sp. (B. pseudomallei, Burkholderia thailandensis, Burkholderia cenocepacia, and Burkholderia multivorans) exhibited different virulence patterns in both simple models, but B. pseudomallei was the most toxic. Using both models, attenuated isolates of B. pseudomallei were selected from a transposon-mutant library and a panel of environmental isolates and reconfirmed by in vitro mouse peritoneal exudate cell association and invasion assays. The distinct pathological patterns of melioidosis were inducted by different selected B. pseudomallei isolates. Fatal melioidosis was induced by the isolates with high virulence in both simple models within 4–5 day, whereas the low-virulence isolates resulted in prolonged survival greater than 30 day. Infection with the isolates having high resistance to D. discoideum predation but a low C. elegans killing effect led to 83% of mice with neurologic melioidosis. By contrast, infection with the isolates having low resistance to D. discoideum predation but high C. elegans killing effect led to 20% cases with inflammation in the salivary glands. Our results indicated that individual B. pseudomallei isolates selected from simple biological models contribute differently to disease progression and/or tissue tropism.

Author Notes

Address correspondence to Yao-Shen Chen, Department of Internal Medicine, Kaohsiung Veterans General Hospital, No. 386, Ta-Chung 1st Rd., Kaohsiung 81346, Taiwan. E-mail: yschen@vghks.gov.tw

Authors’ addresses: Ya-Lei Chen, Duen-Wei Hsu, Jou-An Chen, and Pei-Jyun Shih, Department of Biotechnology, National Kaohsiung Normal University, Kaohsiung, Taiwan, E-mails: dan1001@ms31.hinet.net, duenwei.hsu@gmail.com, kaiko1101@gmail.com, and spg831105@gmail.com. Pei-Tan Hsueh, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, E-mail: mulberrymonster@gmail.com. Susan Lee, Section of Infectious Disease, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, E-mail: ssjlee@vghks.gov.tw. Hsi-Hsun Lin, Institute of Public Health, National Yang-Ming University, Taipei, Taiwan, E-mail: ed100233@yahoo.com.tw. Yao-Shen Chen, Department of Internal Medicine, National Yang-Ming University, Taipei, Taiwan, E-mail: yschen@vghks.gov.tw.

These authors contributed equally to this work.

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