Abstract

Melioidosis is a serious infectious disease endemic to Southeast Asia and Northern Australia. This disease is caused by the Gram-negative bacterium Burkholderia pseudomallei; Burkholderia thailandensis is a closely-related organism known to be avirulent in humans. B. thailandensis has not previously been used to infect Drosophila melanogaster. We examined the effect of B. thailandensis infection on fly survival, on antimicrobial peptide expression, and on phagocytic cells. In the fruit fly, which possesses only an innate immune system, B. thailandensis is highly virulent, causing rapid death when injected or fed. One intriguing aspect of this infection is its temperature dependence: infected flies maintained at 25°C exhibit rapid bacterial proliferation and death in a few days, while infected animals maintained at 18°C exhibit very slow bacterial proliferation and take weeks to die; this effect is due in part to differences in immune activity of the host. Death in this infection is likely due at least in part to a secreted toxin, as injection of flies with sterile B. thailandensis-conditioned medium is able to kill. B. thailandensis infection strongly induces the expression of antimicrobial peptides, but this is insufficient to inhibit bacterial proliferation in infected flies. Finally, the function of fly phagocytes is not affected by B. thailandensis infection. The high virulence of B. thailandensis in the fly suggests the possibility that this organism is a natural pathogen of one or more invertebrates.

Highlights

  • Melioidosis is a serious human and animal disease caused by the Gram-negative bacterium Burkholderia pseudomallei

  • B. thailandensis E264 is pathogenic in Drosophila melanogaster and induces antimicrobial peptides

  • Burkholderia thailandensis E264 (B. thailandensis) is avirulent in people under normal conditions; it is highly pathogenic in wild-type (Oregon-R) D. melanogaster (5–10 days old). 100% of flies injected with B. thailandensis died reliably within 3.5 days of infection [Fig. 1A] and increasing bacterial dose resulted in more rapid mortality [Fig. S1A]

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Summary

Introduction

Melioidosis is a serious human and animal disease caused by the Gram-negative bacterium Burkholderia pseudomallei. Melioidosis can be contracted through damaged skin from B. pseudomalleiinfected soil and water or by inhaling aerosolised bacteria [4]. Melioidosis can manifest itself as a fever, mild or severe septicaemic pneumonia, skin and internal organ abscesses, and neurological conditions, such as brainstem encephalitis [3,5]. The treatment of melioidosis is long and frequently unsuccessful; in many cases the disease recurs [6]. Currie and colleagues conducted a 10-year study of melioidosis patients and found that approximately 86% of patients who suffer septic shock as a result of this infection die [7]. The outcome of melioidosis depends on individual circumstances and risk factors; diabetes, chronic renal disease or alcoholism have been reported to increase the rate of death in melioidosis patients [5,8]

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