Structural studies suggest aggregation as one of the modes of action for teixobactin
Öster, Carl, Walkowiak, Grzegorz P., Hughes, Dallas E., Spoering, Amy L., Peoples, Aaron J., Catherwood, Anita C., Tod, Julie A., Lloyd, Adrian J., Herrmann, Torsten, Lewis, Kim, Dowson, Christopher G. and Lewandowski, Józef R.
Teixobactin is a new promising antibiotic that targets cell wall biosynthesis by binding to lipid II and has no detectable resistance thanks to its unique but yet not fully understood mechanism of operation. To aid in the structure-based design of teixobactin analogues with improved pharmacological properties, we present a 3D structure of native teixobactin in membrane mimetics and characterise its binding to lipid II through a combination of solution NMR and fast (90 kHz) magic angle spinning solid state NMR. Our study provides several new clues to teixobactin's modes of action.
Updates of the in-gel digestion method for protein analysis by mass spectrometry
Goodman JK, Zampronio CG, Jones AME, Hernandez-Fernaud JR
The in‐gel digestion of proteins for analysis by liquid chromatograph mass spectrometry has been used since the early 1990s. Although several improvements have contributed to increasing the quality of the data obtained, many recent publications still use sub‐optimal approaches. We present updates of the in‐gel digestion protocol. The updates are efficient and offer flexibility to be incorporated in any proteomic laboratory.
A GFP-strategy for efficient recombinant protein overexpression and purification in Mycobacterium smegmatis
Anjana Radhakrishnan, Christopher M Furze, Mohd Syed Ahangar and Elizabeth Fullam
One of the major obstacles to obtaining a complete structural and functional understanding of proteins encoded by the Mycobacterium tuberculosis (Mtb) pathogen is due to significant difficulties in producing recombinant mycobacterial proteins. Here we have developed a method for the rapid screening of both protein production and purification strategies of mycobacterial proteins in whole M. smegmatis cells following green fluorescent protein (GFP) fluorescence as an indicator. The GFP system described here will accelerate the production of mycobacterial proteins that can be used to understand the molecular mechanisms of Mtb proteins and facilitate drug discovery efforts
Bayesian inference of ancestral dates on bacterial phylogenetic trees
Xavier Didelot, Nicholas J Croucher, Stephen D Bentley, Simon R Harris, Daniel J Wilson
The sequencing and comparative analysis of a collection of bacterial genomes from a single species or lineage of interest can lead to key insights into its evolution, ecology or epidemiology. The tool of choice for such a study is often to build a phylogenetic tree, and more specifically when possible a dated phylogeny, in which the dates of all common ancestors are estimated. Here, we propose a new Bayesian methodology to construct dated phylogenies which is specifically designed for bacterial genomics.
Dynamical and biological panspermia constraints within multi-planet exosystems
As discoveries of multiple planets in the habitable zone of their parent star mount, developing analytical techniques to quantify extrasolar intra-system panspermia will become increasingly important. Here, we provide user-friendly prescriptions that describe the asteroid impact characteristics which would be necessary to transport life both inwards and outwards within these systems within a single framework. We derive a probability distribution function for life-bearing debris to reach a planetary orbit and describe the survival of microorganisms during planetary ejection, their journey through interplanetary space, and atmospheric entry.
Estimating the efficacy of community-wide use of systemic insecticides in dogs to control zoonotic visceral leishmaniasis: a modelling study in a Brazilian scenario
Systemic insecticides in dogs have been suggested as a public health intervention to prevent human cases of Zoonotic Visceral Leishmaniasis (ZVL) To reduce the number of ZVL cases, a large proportion of dogs in the community should be treated and the systemic insecticide used should be effective in killing phlebotomine flies acting as vectors of L. infantum parasites for a significant amount of time. We used a mathematical model mimicking L. infantum transmission to show that this novel vector control strategy could be effective. We identified the combination of different key parameters (e.g. insecticide efficacy, duration and proportion of dogs treated) that could lead to a significant reduction of the risk of L. infantum infection in humans.