Building a better biofilm - Formation of in vivo-like biofilm structures by Pseudomonas aeruginosa in a porcine model of cystic fibrosis lung infection
Niamh E Harrington, Esther Sweeney, Freya Harrison
Pseudomonas aeruginosa biofilm infections in the cystic fibrosis (CF) lung are highly resistant to current antimicrobial treatments and are associated with increased mortality rates. The existing models for such infections are not able to reliably mimic the clinical biofilms observed. We further optimise an ex vivo pig lung (EVPL) model for P. aeruginosa CF lung infection that can be used to increase understanding of chronic CF biofilm infection. We propose the high-throughput EVPL model as a validated biofilm platform to bridge the gap between in vitro work and CF lung infection. The EVPL model will facilitate discovery of novel infection prevention methods and treatments, and enhanced exploration of biofilm architecture.
Novel markers for high-throughput protoplast-based analyses of phytohormone signaling
Silke Lehmann, Ana Dominguez-Ferreras, Wei-Jie Huang, Katherine Denby, Vardis Ntoukakis, Patrick Schäfer
Phytohormones mediate most diverse processes in plants, ranging from organ development to immune responses. Receptor protein complexes perceive changes in intracellular phytohormone levels and trigger a signaling cascade to effectuate downstream responses. While promoter-reporter constructs have been used successfully to identify internal or external factors that change phytohormone signaling, the range of available marker constructs does not meet the potential of the protoplast technique for large scale approaches. In this study, we recommend novel markers for the analysis of auxin, abscisic acid, cytokinin, salicylic acid and jasmonic acid responses that will facilitate future screens for biological elements and environmental stimuli affecting phytohormone signaling.
Pattern Engineering of Living Bacterial Colonies Using Meniscus Driven Fluidic Channels
Vasily Kantsler, Elena Ontañón-McDonald, Cansu Kuey, Manjari J. Ghanshyam, Maria Chiara Roffin, and Munehiro Asally
Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage l is one of the smallest known repressors (66 amino acids), and activators are typically much larger (e.g., l cI, 237 amino acids). In this study, we show that directed evolution results in a new Cro activator-repressor that functions as efficiently as l cI in vivo. This is the smallest protein activator that enables polymerase recruitment, highlighting the capacity of transcription factors to evolve from very short peptide sequences.
Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function
Bacterial neonatal meningitis results in high mortality and morbidity rates for those affected. Although improvements in diagnosis and treatment have led to a decline in mortality rates, morbidity rates have remained relatively unchanged. Bacterial resistance to antibiotics in this clinical setting further underlines the need for developing other technologies, such as phage therapy. This study illustrates the potential of phage therapy targeting infections such as bacterial neonatal meningitis and is an important step for the continued development of phage therapy targeting antibiotic-resistant bacterial infections generally.
Matt Keeling publications
Policy implications of the potential use of a novel vaccine to prevent infection with Schistosoma mansoni with or without mass drug administration
Klodeta Kura, Benjamin S Collyer, Jaspreet Toor, James E Trusott, T Deidre Hollingsworth, Matt J Keeling, Roy M Anderson
Schistosomiasis is one of the most important neglected tropical diseases (NTDs) affecting millions of people in 79 different countries. The World Health Organization (WHO) has specified two control goals to be achieved by 2020 and 2025 - morbidity control and elimination as a public health problem (EPHP). Mass drug administration (MDA) is the main method for schistosomiasis control but it has sometimes proved difficult to both secure adequate supplies of the most efficacious drug praziquantel to treat the millions infected either annually or biannually, and to achieve high treatment coverage in targeted communities in regions of endemic infection. The development of alternative control methods remains a priority. In this paper, we analyze whether the addition of a novel vaccine alone or in combination with drug treatment, is a more effective control strategy, in terms of achieving the WHO goals, as well as the time and costs to achieve these goals when compared to MDA alone. Vaccine. June 2020
Improving pairwise approximations for network models with susceptible-infected-susceptible dynamics
Leng, Trystan and Keeling, Matthew
Network models of disease spread play an important role in elucidating the impact of long-lasting infectious contacts on the dynamics of epidemics. Moment-closure approximation is a common method of generating low-dimensional deterministic models of epidemics on networks, which has found particular success for diseases with susceptible-infected-recovered (SIR) dynamics. However, the effect of network structure is arguably more important for sexually transmitted infections, which are in general modelled via the susceptible-infected-susceptible (SIS)-paradigm. In this paper, we introduce an improvement to the standard pairwise approximation for network models with SIS-dynamics for two different network structures: the isolated open triple) and the k-regular network. This improvement is achieved by tracking the rate of change of errors between triple values and their standard pairwise approximation.
Microsatellite marker development in the crop wild relative Linum bienne using genome skimming
Beatrice Landoni, Juan Viruel, Rocio Gómez, Robin G. Allaby, Adrian C. Brennan, F.Xavier Picó, and Rocio Pérez‐Barrales
Nuclear microsatellite markers were developed for Linum bienne, the sister species of the crop L. usitatissimum, to provide molecular genetic tools for the investigation of L. bienne genetic diversity and structure. The 16 microsatellite loci developed here can be used for population genetic studies in L. bienne, and 28 additional loci that successfully amplified are available for further testing.avier Picó, and Rocio Pérez‐Barrales