Curcumin rescues Caenorhabditis elegans from a Burkholderia pseudomallei infection

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.

Nematode Peptides with Host-Directed Anti-inflammatory Activity Rescue Caenorhabditis elegans from a Burkholderia pseudomallei Infection

“…Each bacterial culture was aerobically incubated at 37°C unless otherwise stated. The B. pseudomallei Human R15 strain used in this study is a biofilm-producing clinical isolate from Malaysia that is pathogenic in the mouse and C. elegans infection models ( Lee et al, 2007 , 2011 ; Eng and Nathan, 2015 ). All experiments involving B. pseudomallei were performed in a Biosafety Level 2+ laboratory.…”

Anti-infective potential of a quorum modulatory polyherbal extract (Panchvalkal) against certain pathogenic bacteria

“…OD of the supernatant was measured at 240 nm to quantify remaining H2O2 [28], with phosphate buffer as blank. [29] In vivo efficacy of the test formulation at the concentration(s) found effective during in vitro screen was evaluated using the nematode worm Caenorhabditis elegans as the model host. Test bacterium was incubated with the PF for 24 h. Following incubation, OD of the culture suspension was equalized to that of the DMSO control.…”

Resistance to Antibiotics: Are we prepared to Handle This Growing Ghost?

“…C. elegans can prove a useful tool for identification of novel antimicrobials/anti-infectives with a higher probability of clearing subsequent clinical trials. Curcumin was reported for its protective effect in Burkholderia pseudomallei infected C. elegans [144]. Potent QS antagonists were shown to protect C. elegans from killing by P. aeruginosa [145,146] and C. violaceum [147,148].…”