Synergistic activity of cosecreted natural products from amoebae-associated bacteria

Abstract

Investigating microbial interactions from an ecological perspective is a particularly fruitful approach to unveil both new chemistry and bioactivity. Microbial predator-prey interactions in particular rely on natural products as signal or defense molecules. In this context, we identified a grazing-resistant strain, isolated from the bacterivorous amoeba Genome analysis of this bacterium revealed the presence of two biosynthetic gene clusters that were found adjacent to each other on a contiguous stretch of the bacterial genome. Although one cluster codes for the polyketide synthase producing the known antibiotic mupirocin, the other cluster encodes a nonribosomal peptide synthetase leading to the unreported cyclic lipopeptide jessenipeptin. We describe its complete structure elucidation, as well as its synergistic activity against methicillin-resistant , when in combination with mupirocin. Both biosynthetic gene clusters are regulated by quorum-sensing systems, with 3-oxo-decanoyl homoserine lactone (3-oxo-C10-AHL) and hexanoyl homoserine lactone (C6-AHL) being the respective signal molecules. This study highlights the regulation, richness, and complex interplay of bacterial natural products that emerge in the context of microbial competition.

Chemical Interactions of Cryptic Actinomycete Metabolite 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines through Aggregate Formation

“…Thedistribution of the size did not depend on the length of the alkyl chain substituted at C-5 (Supporting Information, Figure S6). In contrast, the CACv alue for 5aTHQ-10n (8)a t5 0 8 8Cw as still 13.0 AE 0.8 mm,s imilar to that of 5aTHQ-9n (5)at258 8C, which revealed the thermal stability of the aggregates of 5aTHQ-10n (8). At low concentrations of 5aTHQ-9n (5; 5 mm), the turbidity was almost zero (Supporting Information, Figure S7).…”

“…The equimolar mixture of the two congeners exhibited growth inhibitory activity comparable with that of 5aTHQ-7n (1), although the concentration of 1 in the mixture was reduced to 50 %ofits total concentration ( Figure 2). This result suggested the possibility that the potencyo ft his active congener 1 was increased by 5aTHQ-10n (8), or that 5aTHQ-10n (8) gained activity in the presence of 5aTHQ-7n (1). Either way, these data indicated the presence of af unctional interaction between the two congeners.…”

“…Both Figure 1. Cells were treated with 5aTHQ-7n( 1), 5aTHQ-10n ( 8), or an equimolar mixture of 5aTHQ-7n (1)a nd 5aTHQ-10n ( 8). Figure 2.…”

“…We investigated the physical nature of the mixture of 5aTHQ-7n (1)a nd 5aTHQ-10n (8). Both compounds hardly showed binding to the lipid membrane at 40 mm (Figure 5a; Supporting Information, Figure S8).…”

“…[7][8][9] Metabolites with different pharmacophores can have different cellular targets in as ame biological pathway,t hus enabling synergistic effect. [7][8][9] Metabolites with different pharmacophores can have different cellular targets in as ame biological pathway,t hus enabling synergistic effect.…”