Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions.

Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here we describe an integrated methodology for the construction and screening of an elicited and pre-fractionated library of marine bacteria. In this pilot study, chemical elicitors were evaluated to mimic the natural environment and to induce the expression of cryptic BGCs in deep-sea bacteria. By integrating high-resolution untargeted metabolomics with cheminformatics analyses, it was possible to visualize, mine, identify and map the chemical and biological space of the elicited bacterial metabolites. The results show that elicited bacterial metabolites correspond to ~45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (~70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (~90% of the collection) and the detection of biological activity. This pilot work pinpoints strategies for constructing and evaluating chemically diverse bacterial natural product libraries towards the identification of novel bacterial metabolites in natural product-based drug discovery pipelines.

Seroprevalence of Leptospira spp infection and its risk factors among domestic dogs in Bogotá, Colombia.

Different analytical tools were used to determine the seroprevalence of and risk factors associated with Leptospira spp infection in 192 domestic dogs (Canis familiaris) in Bogotá, Colombia. Using the microscopic agglutination test (MAT), a battery of 16 Leptospira serovars were tested. The seroprevalence of Leptospira spp was calculated as 36.46% (95% CI 0.30-0.43). A questionnaire was applied to the dogs' owners at the time of sampling and the variables "Water sources near home" and "Dog hunting rodents" were identified as risk factors for leptospirosis occurrence in the urban area of Bogotá. Geographical coordinates relating to the dogs' households were obtained in order to map out the spatial distribution of reactive and unreactive dogs. Additionally, we found that the mean annual precipitation was higher at geographical locations with reactive animals than at those with unreactive dogs (p < 0.05). Preventing exposure of dogs to rodents and waste-water bodies that could be contaminated with Leptospira might effectively reduce occurrences of leptospirosis. Moreover, promoting preventive programs and vaccination of dogs against leptospirosis in areas of higher precipitation and prior to rainy months could be an effective strategy for leptospirosis prevention.