Many microorganisms produce natural products that form the basis of antimicrobials, antivirals, and other drugs. Genome mining is routinely used to complement screening-based workflows to discover novel natural products. Since 2011, the "antibiotics and secondary metabolite analysis shell—antiSMASH" (https://antismash.secondarymetabolites.org/) has supported researchers in their microbial genome mining tasks, both as a free-to-use web server and as a standalone tool under an OSI-approved open-source license. It is currently the most widely used tool for detecting and characterising biosynthetic gene clusters (BGCs) in bacteria and fungi. Here, we present the updated version 6 of antiSMASH. antiSMASH 6 increases the number of supported cluster types from 58 to 71, displays the modular structure of multi-modular BGCs, adds a new BGC comparison algorithm, allows for the integration of results from other prediction tools, and more effectively detects tailoring enzymes in RiPP clusters.
Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Since manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized, for the first time, an open competition, in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to important practical conclusions for users and developers.
Members of the soil-dwelling prokaryotic genus Streptomyces produce many secondary metabolites, including antibiotics and anti-tumour agents. Their formation is coupled with the onset of development, which is triggered by the nutrient status of the habitat. We propose the first complete signalling cascade from nutrient sensing to development and antibiotic biosynthesis. We show that a high concentration of N-acetylglucosamine-perhaps mimicking the accumulation of N-acetylglucosamine after autolytic degradation of the vegetative mycelium-is a major checkpoint for the onset of secondary metabolism. The response is transmitted to antibiotic pathway-specific activators through the pleiotropic transcriptional repressor DasR, the regulon of which also includes all N-acetylglucosamine-related catabolic genes. The results allowed us to devise a new strategy for activating pathways for secondary metabolite biosynthesis. Such 'cryptic' pathways are abundant in actinomycete genomes, thereby offering new prospects in the fight against multiple drug-resistant pathogens and cancers.
Although bacteria frequently live as unicellular organisms, many spend at least part of their lives in complex communities, and some have adopted truly multicellular lifestyles and have abandoned unicellular growth. These transitions to multicellularity have occurred independently several times for various ecological reasons, resulting in a broad range of phenotypes. In this Review, we discuss the strategies that are used by bacteria to form and grow in multicellular structures that have hallmark features of multicellularity, including morphological differentiation, programmed cell death and patterning. In addition, we examine the evolutionary and ecological factors that lead to the wide range of coordinated multicellular behaviours that are observed in bacteria.
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