Latest Publications
Isolation and Characterisation of Novel Lytic Bacteriophages for Therapeutic Applications in Biofilm-Associated Prosthetic Joint Infections
Nathan J. Burton, Luís D R. Melo, Michaël F D. Tadesse, Bethany Pearce, Evangelos Vryonis, Antonia P. Sagona
In this study, we produced a cocktail of novel bacteriophages and assessed their viability to eradicate nosocomial staphylococcal biofilms. Here, we used clinical isolates from prosthetic joint infections to isolate and identify four new bacteriophages from sewage effluent. These novel phages were characterized through electron microscopy and full genome sequencing. Subsequently, we combined them into a phage cocktail, which effectively re-sensitized biofilms to vancomycin and flucloxacillin. Notably, this phage cocktail demonstrated low cytotoxicity in vitro to human epithelial cells, even when used alongside antibiotic treatments. These findings highlight the potential of the phage cocktail as a tool to increase antibiotic treatment success in prosthetic joint infections.
Cutaneous leishmaniasis in British troops following jungle training in Belize: Cumulative incidence and potential risk practices
Rawlings, Ngwa Niba, Bailey, Mark, Craig, Peter, Courtenay, Orin
British soldiers undergoing jungle training in Belize typically experience a relatively low risk of developing cutaneous leishmaniasis. However, an uncharacteristically large outbreak of cutaneous leishmaniasis occurred in 2022. This study aimed to determine the cumulative incidence of the disease and highlight potential shortcomings in personal protective measures to mitigate exposure to sand fly vector bites. A retrospective analysis was conducted on medical records of cutaneous leishmaniasis cases between 2005 and 2022, as well as on questionnaire responses regarding personal protective measures administered to cutaneous leishmaniasis cases in 2022. The reasons behind the unusually high numbers of cutaneous leishmaniasis cases and cumulative incidence in 2022 remain unclear, emphasising the need to improve personal protective measures provision and implement a comprehensive health education programme for troops undergoing jungle training in Belize.
Emergence of synchronised growth oscillations in filamentous fungi
Praneet Prakash, Xue Jiang , Luke Richards, Zoe Schofield, Patrick Schafer Marco Polin, Orkun S. Soyer & Munehiro Asally
Many species of soil fungi grow in the form of branched networks that enable long-range communication and mass flow of nutrient. While there have been investigations on the branching of the fungal networks, their long-term growth dynamics in space and time is still not very well understood. In this study, we monitor the spatio-temporal growth dynamics of the plant-promoting filamentous fungus Serendipita indica for several days in a controlled environment within a microfluidic chamber. We find that S. indica cells display synchronised growth oscillations with the onset of sporulation and at a period of 3 hours. Quantifying this experimental synchronisation of oscillatory dynamics, we show that the synchronisation can be recapitulated by the nearest neighbour Kuramoto model with a millimetre-scale cell-cell coupling.
Complement-mediated killing of Escherichia coli by mechanical destabilization of the cell envelope
Georgina Benn, Christian Bortolini, David M Roberts, Alice L B Pyne, Seamus Holden, Bart W Hoogenboom
Complement proteins eliminate Gram-negative bacteria in the blood via the formation of membrane attack complex (MAC) pores in the outer membrane. However, it remains unclear how outer membrane poration leads to inner membrane permeation and cell lysis. Using atomic force microscopy (AFM) on living Escherichia coli (E. coli), we probed MAC-induced changes in the cell envelope and correlated these with subsequent cell death. We conclude that bacterial cell lysis is only an indirect effect of MAC formation; outer membrane poration leads to mechanical destabilization of the cell envelope, reducing its ability to contain the turgor pressure, leading to inner membrane permeation and cell death.
Comparative genomics and transcriptomics reveal differences in effector complement and expression between races of Fusarium oxysporum f.sp. lactucae
Helen J. Bates, Jamie Pike, R. Jordan Price, Sascha Jenkins, John Connell, Andrew Legg, Andrew Armitage, Richard J. Harrison and John P. Clarkson
This study presents the first genome and transcriptome analyses for Fusarium oxysporum f. sp. lactucae (Fola) which causes Fusarium wilt disease of lettuce. Long-read genome sequencing of three race 1 (Fola1) and three race 4 (Fola4) isolates revealed key differences in putative effector complement between races and with other F. oxysporum ff. spp. following mimp-based bioinformatic analyses.
Early Steps of the Biosynthesis of the Anticancer Antibiotic Pleurotin
Jack A. Weaver, Duha Alkhder, Panward Prasongpholchai, Michaël D. Tadesse, Emmanuel L. de los Santos, Lijiang Song, Christophe Corre, Fabrizio Alberti
Pleurotin is a meroterpenoid specialized metabolite made by the fungus Hohenbuehelia grisea, and it is a lead anticancer molecule due to its irreversible inhibition of the thioredoxin-thioredoxin reductase system. Total synthesis of pleurotin has been achieved, including through a stereoselective route; however, its biosynthesis has not been characterized. In this study, we used isotope-labeled precursor feeding to show that the nonterpenoid quinone ring of pleurotin and its congeners is derived from phenylalanine. This work sets the foundation to fully elucidate the biosynthesis of pleurotin and its congeners, with long-term potential to optimize their production for therapeutic use and engineer the pathway toward the biosynthesis of valuable analogues.