TY - JOUR
T1 - The bacterial signalling molecule indole attenuates the virulence of the fungal pathogen Candida albicans
AU - Oh, S.
AU - Go, G. W.
AU - Mylonakis, E.
AU - Kim, Y.
PY - 2012/9
Y1 - 2012/9
N2 - Aims: Indole is a signalling molecule, produced by a number of Gram-positive and Gram-negative bacteria both in nature as well as clinical environments. Here, we explored the effect of bacterial indole and one of its main derivatives on the virulence of the fungal pathogen Candida albicans. Methods and Results: We found that indole and its derivate indole-3-acetonitrile (IAN) did not affect the viability of C. albicans. Interestingly, indole and IAN repressed C. albicans biofilm formation as well as the attachment of C. albicans to intestinal epithelial HT-29 cells and inhibited the ability of the yeast to make filaments that are the main virulence factor of C. albicans. In addition, we used the heterologous model host Caenorhabditis elegans to demonstrate in vivo that the presence of indole or IAN attenuates C. albicans infection (P = 0·0188 and P < 0·0001 for indole and IAN, respectively, compared to worms exposed to C. albicans DAY185 alone) and decreases fungal colonization in the nematode gut. Importantly, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that in C. albicans, indole and IAN strongly stimulated the transcription of NRG1. Conclusions: Indole and IAN attenuates fungal virulence by regulating the transcription of NRG1, a transcriptional factor that influences filamentation and biofilm formation in C. albicans. Significance and Impact of the Study: Our findings indicate that the bacterial signalling molecules indole and its derivatives play an inter-kingdom role in dynamic network of microbiota and directly modulate the virulence of fungal C. albicans via NRG1.
AB - Aims: Indole is a signalling molecule, produced by a number of Gram-positive and Gram-negative bacteria both in nature as well as clinical environments. Here, we explored the effect of bacterial indole and one of its main derivatives on the virulence of the fungal pathogen Candida albicans. Methods and Results: We found that indole and its derivate indole-3-acetonitrile (IAN) did not affect the viability of C. albicans. Interestingly, indole and IAN repressed C. albicans biofilm formation as well as the attachment of C. albicans to intestinal epithelial HT-29 cells and inhibited the ability of the yeast to make filaments that are the main virulence factor of C. albicans. In addition, we used the heterologous model host Caenorhabditis elegans to demonstrate in vivo that the presence of indole or IAN attenuates C. albicans infection (P = 0·0188 and P < 0·0001 for indole and IAN, respectively, compared to worms exposed to C. albicans DAY185 alone) and decreases fungal colonization in the nematode gut. Importantly, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that in C. albicans, indole and IAN strongly stimulated the transcription of NRG1. Conclusions: Indole and IAN attenuates fungal virulence by regulating the transcription of NRG1, a transcriptional factor that influences filamentation and biofilm formation in C. albicans. Significance and Impact of the Study: Our findings indicate that the bacterial signalling molecules indole and its derivatives play an inter-kingdom role in dynamic network of microbiota and directly modulate the virulence of fungal C. albicans via NRG1.
KW - Biofilms
KW - C. albicans
KW - C. elegans
KW - Indole signalling
KW - Virulence
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U2 - 10.1111/j.1365-2672.2012.05372.x
DO - 10.1111/j.1365-2672.2012.05372.x
M3 - Article
C2 - 22726313
AN - SCOPUS:84865291502
VL - 113
SP - 622
EP - 628
JO - Journal of Applied Microbiology
JF - Journal of Applied Microbiology
SN - 1364-5072
IS - 3
ER -