1887

Abstract

The increase of disease outbreaks caused by species in aquatic organisms as well as in humans, together with the emergence of antibiotic resistance in species, has led to a growing interest in alternative disease control measures. Quorum sensing (QS) is a mechanism for regulating microbial gene expression in a cell density-dependent way. While there is good evidence for the involvement of auto-inducer 2 (AI-2)-based interspecies QS in the control of virulence in multiple species, only few inhibitors of this system are known. From the screening of a small panel of nucleoside analogues for their ability to disturb AI-2-based QS, an adenosine derivative with a -methoxyphenylpropionamide moiety at C-3′ emerged as a promising hit. Its mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of AI-2 QS mutants. Our results indicate that this compound, as well as a truncated analogue lacking the adenine base, block AI-2-based QS without interfering with bacterial growth. The active compounds affected neither the bioluminescence system as such nor the production of AI-2, but most likely interfered with the signal transduction pathway at the level of LuxPQ in . The most active nucleoside analogue (designated LMC-21) was found to reduce the species starvation response, to affect biofilm formation in , and , to reduce pigment and protease production in , and to protect gnotobiotic from -induced mortality.

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2009-12-01
2019-10-22
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