SYNTHESIS AND BIOLOGICAL EVALUATION OF NATURALLY AND NON-NATURALLY OCCURRING HALOGENATED ANALOGUES OF N-ACYL HOMOSERINE LACTONES AS QUORUM SENSING MODULATORS

摘要

Many Gram-negative bacteria secrete N-acylated homoserine lactones (AHLs) in order to control the expression of specific target genes important for phenotype expression (e.g. biofilm formation, bioluminescence, virulence expression, etc.) in a processknown as quorum sensing (QS) (Miller & Bassler, 2001). AHLs consist of a lactone ring adjoined with an acyl chain. The acyl chain can vary in length and oxidation state. The importance of QS for virulence/ biofilm development in pathogenic bacteria nowadays is obvious. Therefore, disruption of QS by synthetic analogues or enzymatic modulation is seen as a new anti-infective and antifouling strategy. In aquatic environments, bacteria interact in various ways with other organisms as pathogens, symbiontsor competitors in the search for resources. Diatoms represent one of the largest and ecologically most significant groups of organisms in nature. They can be found in almost all aquatic environments living in close association with specific populations of heterotrophic bacteria. Several marine organisms have developed defence or deterrence mechanisms, which are often involved in the production of small diffusible signal molecules that can interfere with the QS systems. Diatoms are known to produce a variety of halogenated compounds, which were recently shown to have a role in allelopathic interactions between competing species (Vanelslander et al, 2012). However, not much is known about QS antagonistic compounds derived from diatoms or biological activity of naturally and non-naturally occurring halogenated analogues of N-acyl homoserine lactones.