A Novel Virulent Clinical Isolate of Burkholderia pseudomallei Imported from Thailand Exhibiting Resistance to Trimethoprim-Sulfamethoxazole

Sharon Amit Clinical Microbiology, Sheba Medical Center, Ramat-Gan, Israel;
Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel;

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David Gur Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Moshe Aftalion Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Asaf Biber Infectious Diseases Unit, The Center for Geographic Medicine and Tropical Diseases, Sheba Medical Center, Ramat-Gan, Israel;

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Paula David Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel;

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Inbar Cohen-Gihon Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Hila Cohen Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Ron Alcalay Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Galia Zaide Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Ofir Israeli Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Raphael Ber Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Shahar Rotem Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Ma’ayan Israeli Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Shirley Lazar Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Anat Zvi Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Adi Beth-Din Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Erez Bar-Haim Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Uri Elia Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Shay Weiss Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Ofer Cohen Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Emanuelle Mamroud Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;

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Theodor Chitlaru Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel;
Faculty of Digital Technologies in Medicine, Holon Institute of Technology, Holon, Israel

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ABSTRACT.

We present the investigation of a Burkholderia pseudomallei strain isolated from the urine of a 56-year-old male returning from a recreational trip to Thailand. The patient initially presented with fever and chills, and lobar as well as bladder and prostate involvement was demonstrated on imaging. Treatment first involved trimethoprim-sulfamethoxazole, the backbone of melioidosis therapy, but was discontinued upon the discovery of resistance to the drug through antimicrobial sensitivity testing via broth microdilution. Further analysis included genomic sequencing, immunotyping, and phenotypic assessment, including virulence testing in an animal model. Results indicated that this strain is a distinct, novel variant with antigenic similarity to other Thai strains displaying high virulence, with a significantly low murine intranasal lethal dose 50% inoculum. The emergence of such a strain, particularly if prevalent in tourist destinations in Thailand, could pose a substantial public health risk, highlighting the need for ongoing vigilance among infectious disease specialists and clinical microbiologists.

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Author Notes

Disclosure: Animal studies were approved by the local ethical committee on animal experiments (protocol number Rb-10-18).

Current contact information: Sharon Amit, Clinical Microbiology, Sheba Hospital, Tel Aviv, Israel, E-mail: sharon.amit@sheba.health.gov.il. David Gur, Moshe Aftalion, Inbar Cohen-Gihon, Hila Cohen, Ron Alcalay, Galia Zaide, Ofir Israeli, Raphael Ber, Shahar Rotem, Ma’ayan Israeli, Shirley Lazar, Anat Zvi, Adi Beth-Din, Erez Bar-Haim, Uri Elia, Shay Weiss, Ofer Cohen, Emanuelle Mamroud, and Theodor Chitlaru, Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel, E-mails: gurd@iibr.gov.il, moshea@iibr.gov.il, inbarg@iibr.gov.il, hilac@iibr.gov.il, rona@iibr.gov.il, galiaz@iibr.gov.il, ofiri@iibr.gov.il, raphaelb@iibr.gov.il, shaharr@iibr.gov.il, maayani@iibr.gov.il, shirleyl@iibr.gov.il, anatZ@iibr.gov.il, adib@iibr.gov.il, erezb@iibr.gov.il, urie@iibr.gov.il, shayw@iibr.gov.il, oferc@iibr.gov.il, emmym@iibr.gov.il, and theodorc@iibr.gov.il. Asaf Biber, The Center for Geographic Medicine and Tropical Diseases, The Chaim Sheba Medical Center, Tel Aviv, Israel, E-mail: asafbib@gmail.com. Paula David, Department of Internal Medicine, Sheba Medical Center, Tel Aviv, Israel, E-mail: paula.david@sheba.health.gov.il.

Address correspondence to Theodor Chitlaru, Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel. E-mail: theodorc@iibr.gov.il
  • 1.

    Wiersinga WJ, Virk HS, Torres AG, Currie BJ, Peacock SJ, Dance DAB, Limmathurotsakul D, 2018. Melioidosis. Nat Rev Dis Primers 4: 17107.

  • 2.

    Limmathurotsakul D, et al., 2016. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol 1: 15008.

  • 3.

    Gilad J, Harary I, Dushnitsky T, Schwartz D, Amsalem Y, 2007. Burkholderia mallei and Burkholderia pseudomallei as bioterrorism agents: National aspects of emergency preparedness. Isr Med Assoc J 9: 499503.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Meumann EM, Limmathurotsakul D, Dunachie SJ, Wiersinga WJ, Currie BJ, 2024. Burkholderia pseudomallei and melioidosis. Nat Rev Microbiol 22: 155169.

  • 5.

    Le Tohic S, Montana M, Koch L, Curti C, Vanelle P, 2019. A review of melioidosis cases imported into Europe. Eur J Clin Microbiol Infect Dis 38: 13951408.

  • 6.

    Loveleena, Chaudhry R, Dhawan B, 2004. Melioidosis; the remarkable imitator: Recent perspectives. J Assoc Physicians India 52: 417420.

  • 7.

    Holden MT, et al., 2004. Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei. Proc Natl Acad Sci USA 101: 1424014245.

  • 8.

    Brosh-Nissimov T, et al., 2019. Case Report: Imported melioidosis from Goa, India to Israel, 2018. Am J Trop Med Hyg 101: 580584.

  • 9.

    Cahn A, et al., 2009. Imported melioidosis, Israel, 2008. Emerg Infect Dis 15: 18091811.

  • 10.

    Israeli O, et al., 2019. Draft genome sequence of a rare Israeli clinical isolate of Burkholderia pseudomallei. Microbiol Resour Announc 8: e00281-19.

  • 11.

    Cohen-Gihon I, et al., 2024. Genome sequence of two novel virulent clinical strains of Burkholderia pseudomallei isolated from acute melioidosis cases imported to Israel from India and Thailand. BMC Genom Data 25: 47.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Wick RR, Judd LM, Gorrie CL, Holt KE, 2017. Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLOS Comput Biol 13: e1005595.

  • 13.

    Treangen TJ, Ondov BD, Koren S, Phillippy AM, 2014. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 15: 524.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ, 1990. Basic local alignment search tool. J Mol Biol 215: 403410.

  • 15.

    Podnecky NL, et al., 2017. Mechanisms of resistance to folate pathway inhibitors in Burkholderia pseudomallei: Deviation from the norm. mBio 8: e01357-17.

  • 16.

    Price EP, et al., 2012. Development and validation of Burkholderia pseudomallei-specific real-time PCR assays for clinical, environmental or forensic detection applications. PLoS One 7: e37723.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    CLSI, 2015. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria, 3rd ed. CLSI Guideline M45. Wayne, PA: Clinical and Laboratory Standards Institute.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    CLSI, 2022. Performance Standards for Antimicrobial Susceptibility Testing; 32nd ed. CLSI Supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Lonsway DR, Elrod MG, Kendrick N, Tiller R, Sullivan MM, Edwards JR, Blaney DD, Karlsson M, 2020. Correlation between Etest and reference broth microdilution for antimicrobial susceptibility testing of Burkholderia pseudomallei. Microb Drug Resist 26: 311318.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Fehlberg LC, Nicoletti AG, Ramos AC, Rodrigues-Costa F, de Matos AP, Girardello R, Marques EA, Gales AC, 2016. In vitro susceptibility of Burkholderia cepacia complex isolates: Comparison of disk diffusion, Etest(R), agar dilution, and broth microdilution methods. Diagn Microbiol Infect Dis 86: 422427.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Amemiya K, Bozue JA, Cote CK, Deshazer D, Soffler C, Welkos SL, Worsham PL, 2017. Animal models for melioidosis. Curr Trop Med Rep 4: 208222.

  • 22.

    Titball RW, Russell P, Cuccui J, Easton A, Haque A, Atkins T, Sarkar-Tyson M, Harley V, Wren B, Bancroft GJ, 2008. Burkholderia pseudomallei: Animal models of infection. Trans R Soc Trop Med Hyg 102 (Suppl 1 ):S111S116.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Warawa JM, 2010. Evaluation of surrogate animal models of melioidosis. Front Microbiol 1: 141.

  • 24.

    Massey S, Yeager LA, Blumentritt CA, Vijayakumar S, Sbrana E, Peterson JW, Brasel T, LeDuc JW, Endsley JJ, Torres AG, 2014. Comparative Burkholderia pseudomallei natural history virulence studies using an aerosol murine model of infection. Sci Rep 4: 4305.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Balder R, Lipski S, Lazarus JJ, Grose W, Wooten RM, Hogan RJ, Woods DE, Lafontaine ER, 2010. Identification of Burkholderia mallei and Burkholderia pseudomallei adhesins for human respiratory epithelial cells. BMC Microbiol 10: 250.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Dowling AJ, 2012. Novel gain of function approaches for vaccine candidate identification in Burkholderia pseudomallei. Front Cell Infect Microbiol 2: 139.

  • 27.

    Lazar Adler NR, Govan B, Cullinane M, Harper M, Adler B, Boyce JD, 2009. The molecular and cellular basis of pathogenesis in melioidosis: How does Burkholderia pseudomallei cause disease? FEMS Microbiol Rev 33: 10791099.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Welkos SL, et al., 2015. Characterization of Burkholderia pseudomallei strains using a murine intraperitoneal infection model and in vitro macrophage assays. PLoS One 10: e0124667.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Weppelmann TA, Norris MH, von Fricken ME, Rahman Khan MS, Okech BA, Cannella AP, Schweizer HP, Sanford DC, Tuanyok A, 2018. Seroepidemiology of Burkholderia pseudomallei, etiologic agent of melioidosis, in the Ouest and Sud-Est Departments of Haiti. Am J Trop Med Hyg 99: 12221228.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Rongkard P, et al., 2020. Human immune responses to melioidosis and cross-reactivity to low-virulence Burkholderia species, Thailand. Emerg Infect Dis 26: 463471.

  • 31.

    Scott AE, Laws TR, D’Elia RV, Stokes MG, Nandi T, Williamson ED, Tan P, Prior JL, Atkins TP, 2013. Protection against experimental melioidosis following immunization with live Burkholderia thailandensis expressing a manno-heptose capsule. Clin Vaccine Immunol 20: 10411047.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Sullivan RP, Marshall CS, Anstey NM, Ward L, Currie BJ, 2020. 2020 Review and revision of the 2015 Darwin melioidosis treatment guideline; paradigm drift not shift. PLoS Negl Trop Dis 14: e0008659.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Gee JE, et al., 2022. Multistate outbreak of melioidosis associated with imported aromatherapy spray. N Engl J Med 386: 861868.

  • 34.

    Petras JK, et al., 2022. Notes from the field: Burkholderia pseudomallei detected in a raccoon carcass linked to a multistate aromatherapy-associated melioidosis outbreak—Texas, 2022. MMWR Morb Mortal Wkly Rep 71: 15971598.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Petras JK, et al., 2023. Locally acquired melioidosis linked to environment—Mississippi, 2020–2023. N Engl J Med 389: 23552362.

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