Curcumin rescues Caenorhabditis elegans from a Burkholderia pseudomallei infection

Su Anne Eng, Sheila Nathan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The tropical pathogen Burkholderia pseudomallei requires long-term parenteral antimicrobial treatment to eradicate the pathogen from an infected patient. However, the development of antibiotic resistance is emerging as a threat to this form of treatment. To meet the need for alternative therapeutics, we proposed a screen of natural products for compounds that do not kill the pathogen, but in turn, abrogate bacterial virulence. We suggest that the use of molecules or compounds that are non-bactericidal (bacteriostatic) will reduce or abolish the development of resistance by the pathogen. In this study, we adopted the established Caenorhabditis elegans-B. pseudomallei infection model to screen a collection of natural products for any that are able to extend the survival of B. pseudomallei infected worms. Of the 42 natural products screened, only curcumin significantly improved worm survival following infection whilst not affecting bacterial growth. This suggested that curcumin promoted B. pseudomallei-infected worm survival independent of pathogen killing. To validate that the protective effect of curcumin was directed toward the pathogen, bacteria were treated with curcumin prior to infection. Worms fed with curcumin-treated bacteria survived with a significantly extended mean-time-to-death (p < 0.0001) compared to the untreated control. In in vitro assays, curcumin reduced the activity of known virulence factors (lipase and protease) and biofilm formation. To determine if other bacterial genes were also regulated in the presence of curcumin, a genome-wide transcriptome analysis was performed on curcumin-treated pathogen. A number of genes involved in iron acquisition and transport as well as genes encoding hypothetical proteins were induced in the presence of curcumin. Thus, we propose that curcumin may attenuate B. pseudomallei by modulating the expression of a number of bacterial proteins including lipase and protease as well as biofilm formation whilst concomitantly regulating iron transport and other proteins of unknown function.

Original languageEnglish
Article number290
JournalFrontiers in Microbiology
Volume6
Issue numberAPR
DOIs
Publication statusPublished - 2015

Fingerprint

Burkholderia Infections
Burkholderia pseudomallei
Curcumin
Caenorhabditis elegans
Biological Products
Biofilms
Lipase
Survival
Peptide Hydrolases
Iron
Bacteria
Bacterial Genes
Bacterial Proteins
Gene Expression Profiling
Virulence Factors
Microbial Drug Resistance
Infection
Genes
Virulence

Keywords

  • Antibiotic resistance
  • Bacterial attenuation
  • Burkholderia pseudomallei
  • Caenorhabditis elegans
  • Curcumin

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Curcumin rescues Caenorhabditis elegans from a Burkholderia pseudomallei infection. / Eng, Su Anne; Nathan, Sheila.

In: Frontiers in Microbiology, Vol. 6, No. APR, 290, 2015.

Research output: Contribution to journalArticle

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