1pm – 2.30pm GMT, 24 March 2021 ‐ 1 hour 30 mins
Presentation
Denver Russel Memorial Lecture: FMT and going beyond “What did you say you are going to do!” and C. difficile infection - Professor Julian Marchesi
These talks are led by professionals in their field and are an opportunity to explore research conducted beyond your institution or organisation. This session is themed around medical microbiology.
ECS talks are an opportunity for scientists who are beginning their career to showcase their recent work. The project being presented does not have to be complete, but it’s a great way to practice presenting and answering audience questions in a friendly, supportive environment.
This research sought to develop an ultrasound-responsive agent capable of delivering nitric oxide (NO) contained in lipid-shelled microbubbles (MBs), which can co-administered with antimicrobial compounds for dispersal and elimination of biofilms.
Pseudomonas aeruginosa biofilms were grown on Ibidi® dishes for 48 hours in wound constituent media (WCM), featuring key pathophysiological components of the in vivo wound environment. The anti-biofilm (dispersal) and bactericidal (killing) efficacy of ultrasound-responsive, neutral and cationic lipid-shelled MBs with an air or NO-filled core, was assessed in the presence and absence of sub-inhibitory (4 µg/mL) concentrations of gentamicin. Ultrasound stimulation was carried out for 40 seconds at 0.9 MHz, 20% duty cycle and 500 Hz PRF, achieving an acoustic pressure of 0.5 MPa. Insonified NO-loaded MBs demonstrated a significant 99.9% reduction in viable cells, by enhancing the efficacy of gentamicin. Fluorescence microscopy of treated biofilms showed that the combination of NO and ultrasound-mediated perturbations, achieved a 99.9% reduction in biofilm surface area.
A major challenge in the delivery of NO in antimicrobial therapies is that it has a very limited half-life. By encapsulating it as the gaseous core of an ultrasound-responsive microbubble, NO is shielded from the external environment and allows successful control over its delivery and release. By inducing dispersal and perturbation of the biofilm with NO-loaded MBs, the physical barrier imposed by the extracellular matrix can be negated to improve treatment outcomes.
Biofilms are implicated in over 90% of chronic wounds, the management of which represents an annual cost of £5.6 billion to the NHS as well as significant patient morbidity and mortality. This research is the first of its kind to report the efficacy of lipid-shelled NO-loaded MBs, for the elimination of biofilms with a sub-inhibitory concentration of gentamicin. A proof-of-concept clinically viable translation of this research has been developed, which has the potential to alter the clinical outcome of these patients.
LuTheryn, G., Glynne‐Jones, P., Webb, J. S. and Carugo, D. (2019) ‘Ultrasound‐mediated therapies for the treatment of biofilms in chronic wounds: a review of present knowledge’, Microbial Biotechnology. Wiley Online Library, pp. 1751-7915.13471. doi: 10.1111/1751-7915.13471.
Stride, E. P. and Coussios, C. C. (2009) ‘Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy’, Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 224. doi: 10.1243/09544119JEIM622.
Lafond, M., Shekhar, H., Panmanee, W., Collins, S. D., Palaniappan, A., McDaniel, C. T., Hassett, D. J. and Holland, C. K. (2020) ‘Bactericidal activity of lipid-shelled nitric oxide-loaded microbubbles’, Frontiers in Pharmacology. Frontiers Media S.A., 10. doi: 10.3389/fphar.2019.01540.
Howlin, R. P., Cathie, K., Hall-Stoodley, L., Cornelius, V., Duignan, C., Allan, R. N., Fernandez, B. O., Barraud, N., Bruce, K. D., Jefferies, J., Kelso, M., Kjelleberg, S., Rice, S. A., Rogers, G. B., Pink, S., Smith, C., Sukhtankar, P. S., Salib, R., Legg, J., Carroll, M., Daniels, T., Feelisch, M., Stoodley, P., Clarke, S. C., Connett, G., Faust, S. N. and Webb, J. S. (2017) ‘Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis’, Molecular Therapy. Cell Press, 25(9), pp. 2104–2116. doi: 10.1016/J.YMTHE.2017.06.021
Cardiff University
The human microbiome has recently been found to be an integral part of human biology. For many years it was viewed as a source of infection, but now we know it is an essential component of the host and needed for normal development and function. Professor Julian Marchesi's research since 2001 has focused on understanding the roles that the bacterial component of the microbiome plays in maintaining health and promoting diseases.
Some people are more attractive than others to mosquitoes, and consequently at higher risk of contracting vector borne diseases. The skin microbiome has a key role in producing volatiles which make up distinctive body odour profiles. Here, we aimed to identify differentially abundant bacteria between attractive and poorly attractive groups involved in production of repellent body odour.
We used behavioural assays to measure attractiveness of participants to Anopheles coluzzii mosquitoes, 16S rRNA amplicon sequencing of the bacteria on human skin and gas chromatography of volatiles in body odour. We found differences in skin microbiome composition between the highly and poorly attractive groups. We identified eight differentially abundant amplicon sequence variants between poorly and highly attractive groups of participants. We found strong associations between the differentially abundant genera identified and known Anopheles attractants.
Bacterial genera we have identified explain some of the differences in attractiveness to mosquitoes between highly and poorly attractive people.
Understanding of the bacteria on human skin and associated volatile compounds within body odour offers potential for development of next generation vector control tools in the future.