Epistasis refers to the dependence of a mutation on other mutation(s) and the genetic context in general. In the context of human disorders, epistasis complicates the spectrum of disease symptoms and has been proposed as a major contributor to variations in disease outcome. The nonadditive relationship between mutations and the lack of complete understanding of the underlying physiological effects limit our ability to predict phenotypic outcome. Here, we report positive epistasis between intragenic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)—the gene responsible for cystic fibrosis (CF) pathology. We identified a synonymous single-nucleotide polymorphism (sSNP) that is invariant for the CFTR amino acid sequence but inverts translation speed at the affected codon. This sSNP in cis exhibits positive epistatic effects on some CF disease–causing missense mutations. Individually, both mutations alter CFTR structure and function, yet when combined, they lead to enhanced protein expression and activity. The most robust effect was observed when the sSNP was present in combination with missense mutations that, along with the primary amino acid change, also alter the speed of translation at the affected codon. Functional studies revealed that synergistic alteration in ribosomal velocity is the underlying mechanism; alteration of translation speed likely increases the time window for establishing crucial domain–domain interactions that are otherwise perturbed by each individual mutation.

The actinomycetes are Gram-positive bacteria belonging to the order Actinomycetales within the phylum Actinobacteria . They include members with significant economic and medical importance, for example filamentous actinomycetes such as Streptomyces species, which have a propensity to produce a plethora of bioactive secondary metabolites and form symbioses with higher organisms, such as plants and insects. Studying these bacteria is challenging, but also fascinating and very rewarding. As a Microbiology Society initiative, members of the actinomycete research community have been developing a Wikipedia-style resource, called ActinoBase, the purpose of which is to aid in the study of these filamentous bacteria. This review will highlight 10 publications from 2019 that have been of special interest to the ActinoBase community, covering 4 major components of actinomycete research: (i) development and regulation; (ii) specialized metabolites; (iii) ecology and host interactions; and (iv) technology and methodology.

Here, we characterize an uncommon set of telomeres from Streptomyces rimosus ATCC 10970, the parental strain of a lineage of one of the earliest-discovered antibiotic producers. Following the closure of its genome sequence, we compared unusual telomeres from this organism with the other five classes of replicon ends found amongst streptomycetes. Closed replicons of streptomycete chromosomes were organized with respect to their phylogeny and physical orientation, which demonstrated that different telomeres were not associated with particular clades and are likely shared amongst different strains by plasmid-driven horizontal gene transfer. Furthermore, we identified a ~50 kb origin island with conserved synteny that is located at the core of all streptomycete chromosomes and forms an axis around which symmetrical chromosome inversions can take place. Despite this chromosomal bilateral symmetry, a bias in parS sites to the right of oriC is maintained across the family Streptomycetaceae and suggests that the formation of ParB/parS nucleoprotein complexes on the right replichore is a conserved feature in streptomycetes. Consequently, our studies reveal novel features of linear bacterial replicons that, through their manipulation, may lead to improvements in growth and productivity of this important industrial group of bacteria.

Actinobacteria is an ancient phylum of Gram-positive bacteria with a characteristic high GC content to their DNA. The ActinoBase Wiki is focused on the filamentous actinobacteria, such as Streptomyces species, and the techniques and growth conditions used to study them. These organisms are studied because of their complex developmental life cycles and diverse specialised metabolism which produces many of the antibiotics currently used in the clinic. ActinoBase is a community effort that provides valuable and freely accessible resources, including protocols and practical information about filamentous actinobacteria. It is aimed at enabling knowledge exchange between members of the international research community working with these fascinating bacteria. ActinoBase is an anchor platform that underpins worldwide efforts to understand the ecology, biology and metabolic potential of these organisms. There are two key differences that set ActinoBase apart from other Wiki-based platforms: [] ActinoBase is specifically aimed at researchers working on filamentous actinobacteria and is tailored to help users overcome challenges working with these bacteria and [] it provides a freely accessible resource with global networking opportunities for researchers with a broad range of experience in this field.

Endophytic actinobacteria offer great potential as a source of novel bioactive compounds. In order to investigate the potential for the production of secondary metabolites by endophytes, we recovered a filamentous microorgansism from the tree Antidesma neurocarpum Miq. After phenotypic analysis and whole genome sequencing we demonstrated that this organism, SUK42 was a member of the actinobacterial genus Kitasatospora. This strain has a small genome in comparison with other type strains of this genus and has lost metabolic pathways associated with Stress Response, Nitrogen Metabolism and Secondary Metabolism. Despite this SUK42 can grow well in a laboratory environment and encodes a core genome that is consistent with other members of the genus. Finally, in contrast to other members of Kitasatospora, SUK42 encodes saccharide secondary metabolite biosynthetic gene clusters, one of which with similarity to the acarviostatin cluster, the product of which displays α-amylase inhibitory activity. As extracts of the host plant demonstrate this inhibitory activity, it suggests that the potential medicinal properties of A. neurocarpum Miq might be provided by the endophytic partner and illustrate the potential for exploitation of endophytes for clinical or industrial uses.