Biology subjects

Harrison, F.

Publications and source records attributed to Harrison, F..

22 records · Page 2Linked to original sources

bioRxiv2019

An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic Staphylococcus aureus infection

Staphylococcus aureus is one of the most prevalent organisms isolated from the airways of people with cystic fibrosis (CF), predominantly early in life. Yet its role in the pathology of lung disease is poorly understood. Clinical studies are limited in scope by age and health of participants and in vitro studies are not always able to accurately recapitulate chronic disease characteristics such as the development of small colony variants. Further, animal models also do not fully represent features of clinical disease: in particular, mice are not readily colonized by S. aureus and when infection is established it leads to the formation of abscesses, a phenomenon almost never observed in the human CF lung. Here, we present details of the development of an existing ex vivo pig lung model of CF infection to investigate the growth of S. aureus. We show that S. aureus is able to establish infection and demonstrates clinically significant characteristics including small colony variant phenotype, increased antibiotic tolerance and preferential localisation in mucus. Tissue invasion and the formation of abscesses were not observed, in line with clinical data.

microbiology↗

bioRxiv2018

Datamining a medieval medical text reveals patterns in ingredient choice that reflect biological activity against the causative agents of specified infections

The pharmacopeia used by physicians and lay people in medieval Europe has largely been dismissed as placebo or superstition. While we now recognise that some of the materia medica used by medieval physicians could have had useful biological properties, research in this area is limited by the labour-intensive process of searching and interpreting historical medical texts. Here, we demonstrate the potential power of turning medieval medical texts into contextualised electronic databases amenable to exploration by algorithm. We use established methodologies from network science to reveal statistically significant patterns in ingredient selection and usage in a key text, the fifteenth-century Lylye of Medicynes, focusing on remedies to treat symptoms of microbial infection. We discuss the potential that these patterns reflect rational medical decisions. In providing a worked example of data-driven textual analysis, we demonstrate the potential of this approach to encourage interdisciplinary collaboration and to shine a new light on the ethnopharmacology of historical medical texts.

scientific communication and education↗

bioRxiv2016

The social evolution of siderophore production in Pseudomonas aeruginosa is environmentally determined.

Bacteria secrete various exoproducts whose benefits can be shared by all cells in the vicinity. The potential importance of these \"public goods\" in bacterial evolutionary ecology has been extensively studied. Cheating by siderophore-null mutants of the opportunistic pathogen Pseudomonas aeruginosa has received particular attention. The potential of siderophore mutants to attenuate virulence, and the possibility of exploiting this for clinical ends, have generated a wealth of publications. However, the possibility that genotype {middle dot} environment interactions govern the evolutionary consequences of siderophore loss has been almost entirely ignored. A review of the available literature revealed (i) widespread use of an undefined mutant as a siderophore cheat; and (ii) a reliance on experiments conducted in iron-limited minimal medium. Whole genome sequencing of the undefined mutant revealed a range of mutations affecting phenotypes other than siderophore production. We then conducted cheating assays using defined deletion mutants, grown in conditions designed to model infected fluids and tissue in CF lung infection and non-healing wounds. Depending on the environment, we found that siderophore loss could lead to cheating, simple fitness defects, or no fitness effect at all. It is therefore crucial to develop appropriate in vitro growth conditions in order to better predict the social evolution of traits in vivo.

microbiology↗

bioRxiv2016

The fitness of Pseudomonas aeruginosa quorum sensing signal cheats is influenced by the diffusivity of the environment

Experiments examining the social dynamics of bacterial quorum sensing (QS) have focused on mutants which do not respond to signals, and the role of QS-regulated exoproducts as public goods. The potential for QS signal molecules to themselves be social public goods has received much less attention. Here, we analyse how signal-deficient (lasI-) mutants of the opportunistic pathogen Pseudomonas aeruginosa interact with wild-type cells in an environment where QS is required for growth. We show that when growth requires a private intracellular metabolic mechanism activated by the presence of QS signal, lasI- mutants act as social cheats and outcompete signal-producing wild-type bacteria in mixed cultures, because they can use the signals produced by wild type cells. However, reducing the ability of signal molecules to diffuse through the growth medium, results in signal molecules becoming less accessible to mutants, leading to reduced cheating. Our results indicate that QS signal molecules can be considered as social public goods in a way that has been previously described for other exoproducts, but that spatial structuring of populations reduces exploitation by non-cooperative signal cheats.\n\nImportanceBacteria communicate via signaling molecules to regulate the expression of a whole range of genes. This process, termed quorum sensing (QS), moderates bacterial metabolism in many environmental conditions, from soil and water (where QS-regulated genes influence nutrient cycling) to animal hosts (where QS-regulated genes determine pathogen virulence). Understanding the ecology of QS could therefore yield vital clues as to how we might modify bacterial behaviour for environmental or clinical gains. Here, we demonstrate that QS signals act as shareable public goods. This means that their evolution, and therefore population-level responses to interference with QS, will be constrained by population structure. Further, we show that environmental structure (constraints on signal diffusion) alters the accessibility of QS signals and demonstrates that we need to consider population and environmental structure to help us further our understanding of QS signaling systems.

microbiology↗