Development and validation of an updated computational model of Streptomyces coelicolor primary and secondary metabolism.

BACKGROUND: Streptomyces species produce a vast diversity of secondary metabolites of clinical and biotechnological importance, in particular antibiotics. Recent developments in metabolic engineering, synthetic and systems biology have opened new opportunities to exploit Streptomyces secondary metabolism, but achieving industry-level production without time-consuming optimization has remained challenging. Genome-scale metabolic modelling has been shown to be a powerful tool to guide metabolic engineering strategies for accelerated strain optimization, and several generations of models of Streptomyces metabolism have been developed for this purpose. RESULTS: Here, we present the most recent update of a genome-scale stoichiometric constraint-based model of the metabolism of Streptomyces coelicolor, the major model organism for the production of antibiotics in the genus. We show that the updated model enables better metabolic flux and biomass predictions and facilitates the integrative analysis of multi-omics data such as transcriptomics, proteomics and metabolomics. CONCLUSIONS: The updated model presented here provides an enhanced basis for the next generation of metabolic engineering attempts in Streptomyces.

The human microbial exposome: expanding the Exposome-Explorer database with gut microbial metabolites.

Metabolites produced by the gut microbiota play an important role in the cross-talk with the human host. Many microbial metabolites are biologically active and can pass the gut barrier and make it into the systemic circulation, where they form the gut microbial exposome, i.e. the totality of gut microbial metabolites in body fluids or tissues of the host. A major difficulty faced when studying the microbial exposome and its role in health and diseases is to differentiate metabolites solely or partially derived from microbial metabolism from those produced by the host or coming from the diet. Our objective was to collect data from the scientific literature and build a database on gut microbial metabolites and on evidence of their microbial origin. Three types of evidence on the microbial origin of the gut microbial exposome were defined: (1) metabolites are produced in vitro by human faecal bacteria; (2) metabolites show reduced concentrations in humans or experimental animals upon treatment with antibiotics; (3) metabolites show reduced concentrations in germ-free animals when compared with conventional animals. Data was manually collected from peer-reviewed publications and inserted in the Exposome-Explorer database. Furthermore, to explore the chemical space of the microbial exposome and predict metabolites uniquely formed by the microbiota, genome-scale metabolic models (GSMMs) of gut bacterial strains and humans were compared. A total of 1848 records on one or more types of evidence on the gut microbial origin of 457 metabolites was collected in Exposome-Explorer. Data on their known precursors and concentrations in human blood, urine and faeces was also collected. About 66% of the predicted gut microbial metabolites (n = 1543) were found to be unique microbial metabolites not found in the human GSMM, neither in the list of 457 metabolites curated in Exposome-Explorer, and can be targets for new experimental studies. This new data on the gut microbial exposome, freely available in Exposome-Explorer ( http://exposome-explorer.iarc.fr/ ), will help researchers to identify poorly studied microbial metabolites to be considered in future studies on the gut microbiota, and study their functionalities and role in health and diseases.

Comparison of breath-guards and face-masks on droplet spread in eye clinics.

INTRODUCTION: COVID-19 has impacted ophthalmic care delivery, with many units closed and several ophthalmologists catching COVID-19. Understanding droplet spread in clinical and training settings is paramount in maintaining productivity, while keeping patients and practitioners safe. OBJECTIVES: We aimed to assess the effectiveness of a breath-guard and a face mask in reducing droplet spread within an eye clinic. METHODS: We performed a randomised trial of droplet spread using a fluorescein-based cough model to assess the efficacy of a 'breath-guard' and 'face-mask' to prevent the spread of droplets. The 'cough' spray was collected on calibrated paper targets. The sheets were photographed under blue light, with an orange filter on the camera; the position and size of the spots was measured with software originally developed for astronomy. We performed 44 randomised coughs; 22 controls with no breath-guard or face-mask, 11 using breath-guard only and 11 with combined breath-guard and face-mask. We compared both the number of droplets detected and the area of drops on paper targets. RESULTS: The average number of droplets in the controls was 19,430 (SE 2691), the breath-guard group 80 (SE 19) droplets (P < 0.001); in the combined In the group the count was 5 (SE 2), a significant drop from shield only (P = 0.008). The mean areas of each target covered by spots for each group were 5.7 ± 0.857% (95% CI), 0.004 ± 0.000104% (95% CI) and 0.001 ± 0.0000627% (95% CI) respectively. CONCLUSION: These results show that the breath-guard alone reduced the droplet count by 99.93%. Combining the breath-guard with a face-mask reduced the droplet count by over 99.98%. Breath-guards are widely used in clinics and this trial demonstrates that breath-guards with face-masks effectively block droplet spray.

Detection of dental fomites using topical fluorescein.

Background Thorough disinfection of dental facilities is of paramount importance during the COVID-19 pandemic. Patients, clinicians, students and nurses can all be infected by aerosols and dental droplets bearing COVID-19. However, droplets are transparent and often microscopic, so are difficult to detect in clinical practice.Methods To better understand the spread of dental droplets, we stained the dental irrigant with fluorescein and performed a series of procedures on a dental manikin. We then viewed droplets and fomite spread around the dental chair, with and without an ultraviolet (UV) light.Results Observations without the UV light showed minimal or no fluid spread. However, using UV light, we detected fluorescein on the dentist, chairs and the handpiece, as well as splatter on the floor and on the instrument tray. This was of educational value to the staff, who were reminded how far droplets had spread.Conclusion Fluorescein facilitates the detection of droplet spread and helps clinical staff to see high-risk areas that require in-depth cleaning. As clinical grade fluorescein is cheap and widely available, this technique may be useful for dental practices to train staff in the thorough decontamination of the clinical environment.

Networks and Graphs Discovery in Metabolomics Data Analysis and Interpretation.

Both targeted and untargeted mass spectrometry-based metabolomics approaches are used to understand the metabolic processes taking place in various organisms, from prokaryotes, plants, fungi to animals and humans. Untargeted approaches allow to detect as many metabolites as possible at once, identify unexpected metabolic changes, and characterize novel metabolites in biological samples. However, the identification of metabolites and the biological interpretation of such large and complex datasets remain challenging. One approach to address these challenges is considering that metabolites are connected through informative relationships. Such relationships can be formalized as networks, where the nodes correspond to the metabolites or features (when there is no or only partial identification), and edges connect nodes if the corresponding metabolites are related. Several networks can be built from a single dataset (or a list of metabolites), where each network represents different relationships, such as statistical (correlated metabolites), biochemical (known or putative substrates and products of reactions), or chemical (structural similarities, ontological relations). Once these networks are built, they can subsequently be mined using algorithms from network (or graph) theory to gain insights into metabolism. For instance, we can connect metabolites based on prior knowledge on enzymatic reactions, then provide suggestions for potential metabolite identifications, or detect clusters of co-regulated metabolites. In this review, we first aim at settling a nomenclature and formalism to avoid confusion when referring to different networks used in the field of metabolomics. Then, we present the state of the art of network-based methods for mass spectrometry-based metabolomics data analysis, as well as future developments expected in this area. We cover the use of networks applications using biochemical reactions, mass spectrometry features, chemical structural similarities, and correlations between metabolites. We also describe the application of knowledge networks such as metabolic reaction networks. Finally, we discuss the possibility of combining different networks to analyze and interpret them simultaneously.

Are synthetic biology standards applicable in everyday research practice?

The issue of standardization in synthetic biology is a recurring one. As a discipline that incorporates engineering principles into biological designs, synthetic biology needs effective ways to communicate results and allow different researchers (both academic and industrial) to build upon previous results and improve on existing designs. An aspect that is left out of the discussions, especially when they happen at the level of academic and industrial consortia or policymaking, is whether or not standards are applicable or even useful in everyday research practice. In this caucus article, we examine this particular issue with the hope of including it in the standardization discussions agenda and provide insights into a topic that synthetic biology researchers experience daily.

CASH 2021: commercial access and space habitation.

Issues about commercialization of space have been a growing concern in the past decade for the space community. This paper focuses on the work from a team of 51 students attending the Summer Session Program of the International Space University in Bremen, Germany. CASH 2021 (Commercial Access and Space Habitation) documents a plan that identifies commercial opportunities for space utilization that will extend human presence in space, and will chart the way forward for the next 20 years. The group selected four commercial sectors that show the most promise for the future: tourism, entertainment, space system service, assembly and debris removal, and research and development/production. The content of this document presents the results of their research. Historical activities in each of the commercial sectors are reviewed along with the current market situation. To provide a coherent background for future commercialization possibilities a scenario has been developed. This scenario includes a postulated upon ideal future and includes social, political and economic factors that may affect the space industry over the timeline of the study. The study also presents a roadmap, within the limited optimistic scenario developed, for the successful commercialization of space leading to future human presence in space. A broad range of commercially viable opportunities, not only within the current limits of the International Space Station, but also among the many new developments that are expected by 2021 are discussed.