SummaryBacteria, which prey on other microorganisms, are commonly found in the environment. While some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. Anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. Consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. Here, we will present the results from recent chemical investigations of this bacterial group, compare the biosynthetic potential with that of non-predatory bacteria and discuss the link between predation and secondary metabolism.
A bioactivity-guided approach was taken to identify the acetylcholinesterase (AChE) inhibitory agents in the ethanolic extract of Chuquiraga erinacea D. Don. subsp. erinacea leaves using a bioautographic method. This permitted the isolation of the pentacyclic triterpenes calenduladiol (1), faradiol (2), heliantriol B2 (3), lupeol (4), and a mixture of alpha-and beta-amyrin ( 5A and 5B) as active constituents. Pseudotaraxasterol (6) and taraxasterol (7) were also isolated from this extract and showed no activity at the same analytical conditions. Compound 1 showed the highest AChE inhibitory activity with 31.2 % of inhibition at 0.5 mM. Looking forward to improve the water solubility of the active compounds, the sodium sulfate ester of 1 was prepared by reaction with the (CH3)3N.SO3 complex. The semisynthetic derivative disodium calenduladiol disulfate (8) elicited higher AChE inhibition than 1 with 94.1 % of inhibition at 0.5 mM (IC (50) = 0.190 +/- 0.003 mM). Compounds 1, 2, 3, 5, 6, and 7 are reported here for the first time in C. erinacea. This is the first report of AChE inhibition from calenduladiol (1) as well as from a sulfate derived from a natural product.
Nematode parasites cause substantial morbidity to billions of people and considerable losses in livestock and food crops. The repertoire of effective anthelmintic compounds for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance has become a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system, we here screened the nematicidal potential of novel imidazolium and imidazole derivatives. One of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C. elegans at both mature and immature stages. This lethal effect appears to be specific because DII concentrations which prove to be toxic to C. elegans do not induce significant lethality on bacteria, Drosophila melanogaster, and HEK-293 cells. Our analysis of DII action on C. elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 has been largely reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously unidentified UNC-29-containing muscle AChR, different from the classical L-AChR. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. Its lethality on C. elegans, its harmlessness in non-nematode species and its novel and dual mechanism of action make DII a promising candidate compound for anthelmintic therapy.
Aims
Cells limit the cell number of dense biofilms by releasing self‐inhibitory molecules. Here, we aim to assess the effectiveness of yeast quorum sensing (QS) molecules and the antifungal agent natamycin against yeast biofilms of strains commonly isolated from fruit juice ultrafiltration membranes.
Methods and Results
Yeast QS molecules, such as tyrosol, 2‐phenylethanol and farnesol, were detected by solvent extraction and HS‐SPME GC‐MS in Candida tropicalis cultures. The effect of QS molecules on mono‐ and multispecies biofilms formed by Rhodotorula mucilaginosa, C. tropicalis, Candida krusei and Candida kefyr was evaluated by plate count and epifluorescence microscopy. Farnesol caused a decrease in cell number and disrupted mono‐ and multispecies yeast biofilms during adhesion (0·6 mmol l−1). 2‐phenyl ethanol 1·2 mmol l−1 stimulated biofilm density and increased cell number in both mono‐ and multispecies biofilms, while tyrosol did not show effects when tested against C. tropicalis biofilms (0·05–1·2 mmol l−1). Natamycin caused a strong decrease in cell number and disruption of biofilm structure in C. tropicalis biofilms at high concentrations (0·3–1·2 mmol l−1). The combination of farnesol 0·6 mmol l−1 and natamycin at 0·01 mmol l−1, the maximum concentration of natamycin accepted for direct addition into fruit juices, effectively reduced cell counts and disrupted the structure of C. tropicalis biofilms.
Conclusion
Farnesol 0·6 mmol l−1 significantly increased the inhibition exerted by natamycin 0·01 mmol l−1 (~5 ppm) reducing biofilm development from juice on stainless steel surfaces.
Significance and Impact of the Study
These results support the use of QS molecules as biofilm inhibitors in beverages and would certainly inspire the design of novel preservative and cleaning products for the food industry based on combinatory approaches.
A Gram-stain-positive, spore-forming actinomycete strain (HKI0641 T ) was isolated from a soil sample collected in the Black Forest, Germany. During screening for antimicrobial natural products this bacterium was identified as a producer of the antibiotic telomycin. Morphological characteristics and chemotaxonomic data indicated that the strain belonged to the genus Micromonospora. The peptidoglycan of strain HKI0641T contained meso-diaminopimelic acid, and the fatty acid profile consisted predominantly of anteiso-C 15 : 0 , iso-C 15 : 0 , iso-C 16 : 0 and C 16 : 0 . MK-10(H 4 ), MK-10(H 2 ) and MK-10 were identified as the major menaquinones. To determine the taxonomic positioning of strain HKI0641T , we computed a binary tanglegram of two rooted phylogenetic trees that were based upon 16S rRNA and gyrB gene sequences. The comparative analysis of the two common classification methods strongly supported the phylogenetic affiliation with the genus Micromonospora, but it also revealed discrepancies in the assignment at the level of the genomic species. 16S rRNA gene sequence analysis identified Micromonospora coxensis DSM 45161 T (99.1 % sequence similarity) and Micromonospora marina DSM 45555 T (99.0 %) as the nearest taxonomic neighbours, whereas the gyrB sequence of strain HKI0641 T indicated a closer relationship to Micromonospora aurantiaca DSM 43813 T (95.1 %). By means of DNA-DNA hybridization experiments, it was possible to resolve this issue and to clearly differentiate strain HKI0641 T from other species of the genus Micromonospora. The type strains of the aforementioned species of the genus Micromonospora could be further distinguished from strain HKI0641 T by several phenotypic properties, such as colony colour, NaCl tolerance and the utilization of carbon sources. The isolate was therefore assigned to a novel species of the genus Micromonospora, for which the name Micromonospora schwarzwaldensis sp. nov. is proposed. The type strain is HKI0641 T (5DSM 45708 T 5CIP 110415 T ).
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