New approaches to antimicrobial discovery are needed to address the growing threat of antibiotic resistance. The Streptomyces genus, a proven source of antibiotics, is recognized as having a large reservoir of untapped secondary metabolic genes, many of which are likely to produce uncharacterized compounds. However, most of these compounds are currently inaccessible, as they are not expressed under standard laboratory conditions. Here, we present a novel methodology for activating these "cryptic" metabolites by heterologously expressing a constitutively active pleiotropic regulator. By screening wild Streptomyces isolates, we identified the antibiotic siamycin-I, a lasso peptide that we show is active against multidrug pathogens. We further revealed that siamycin-I interferes with cell wall integrity via lipid II. This new technology has the potential to be broadly applied for use in the discovery of additional "cryptic" metabolites.

Antibiotic biosynthesis in the streptomycetes is a complex and highly regulated process. Here, we provide evidence for the contribution of a novel genetic locus to antibiotic production in Streptomyces coelicolor. The overexpression of a gene cluster comprising four protein-encoding genes (abeABCD) and an antisense RNAencoding gene (␣-abeA) stimulated the production of the blue-pigmented metabolite actinorhodin on solid medium. Actinorhodin production also was enhanced by the overexpression of an adjacent gene (abeR) encoding a predicted Streptomyces antibiotic regulatory protein (SARP), while the deletion of this gene impaired actinorhodin production. We found the abe genes to be differentially regulated and controlled at multiple levels. Upstream of abeA was a promoter that directed the transcription of abeABCD at a low but constitutive level. The expression of abeBCD was, however, significantly upregulated at a time that coincided with the initiation of aerial development and the onset of secondary metabolism; this expression was activated by the binding of AbeR to four heptameric repeats upstream of a promoter within abeA. Expressed divergently to the abeBCD promoter was ␣-abeA, whose expression mirrored that of abeBCD but did not require activation by AbeR. Instead, ␣-abeA transcript levels were subject to negative control by the double-strand-specific RNase, RNase III.

Purpose: To describe the perspectives of people with stroke and their physiotherapists on the use of biomechanics technology to assess balance and mobility. Methods: This qualitative study used semi-structured interviews with patients with stroke and a focus group with their physiotherapists. Coding of interview and focus-group data used a line-by-line inductive approach, with qualitative software to develop codes into themes. Results: The quantitative data from the assessment were seen as beneficial to providing patients with insight into balance and mobility problems. Physiotherapists found that the assessment confirmed clinical reasoning and aided in precise evaluation of progress but expressed mixed opinions as to whether treatment choice was influenced. Patients would have liked more communication regarding the purpose of the assessment. Patients also stated that trust in their physiotherapists helped them overcome anxieties and that confidence was gained through exposure to more challenging balance assessments. Physiotherapists advocated for the use of a harness system to safely incorporate reactive balance control assessment and training into practice. Conclusion: Both patients and therapists saw value in the quantitative data provided by the assessment. Regardless of the technology used, patients value a strong physiotherapistpatient relationship. Ongoing collaboration between clinicians and researchers should guide the evolution of technology into clinically useful tools.Key Words: patient outcome assessment, technology; postural balance; stroke. RÉ SUMÉObjectif : Dé crire les vues des gens ayant subi une attaque et de leurs physiothé rapeutes au sujet du recours à la biomé canique pour l'é valuation de l'é quilibre et de la mobilité . Mé thodes : Dans cette é tude qualitative, on a mené des interviews semi-structuré es auprè s de patients ayant subi un accident vasculaire cé ré bral et organisé un groupe de discussion avec leurs physiothé rapeutes. Pour coder les donné es de ces interviews et de ce groupe, on a procé dé par induction ligne à ligne en se servant d'un logiciel qualitatif pour convertir les codes en thè mes. Ré sultats : On a jugé que les donné es quantitatives de cette é valuation pouvaient é clairer les patients sur les problè mes d'é quilibre et de mobilité . Les physiothé rapeutes ont constaté que l'é valuation confirmait le raisonnement clinique et contribuait à une appré ciation pré cise des progrè s, mais leurs opinions é taient partagé es en matiè re d'incidence sur le choix de traitement. Les patients auraient voulu plus de communication sur le but de l'é valuation. Ils ont aussi dit que la confiance dans leurs physiothé rapeutes les aidait à vaincre leurs anxié té s et que cette confiance s'acqué rait par une exposition à des é valuations d'é quilibre plus exigeantes. Les physiothé rapeutes pré conisaient l'emploi d'un systè me de harnais pour une inté gration en toute sé curité à leur pratique de l'é valuation et de la formation en maîtrise ré active de l'é quilibre. Co...