Latest Publications
Bacterial catabolism of membrane phospholipids links marine biogeochemical cycles
Linda M. Westermann, Ian D. E. A. Lidbury Chun-Yang Li, Ning Wang, Andrew R. J. Murphy, Maria del Mar Aguilo Ferretjans, Mussa Quareshy, Muralidharan Shanmugan , Alberto Torcello-Requena, Eleonora Silvano, Yu-Zhong Zhang, Claudia A. Blindauer, Yin Chen, David J. Scanlan
In marine systems, the availability of inorganic phosphate can limit primary production leading to bacterial and phytoplankton utilization of the plethora of organic forms available. Among these are phospholipids that form the lipid bilayer of all cells as well as released extracellular vesicles. However, information on phospholipid degradation is almost nonexistent despite their relevance for biogeochemical cycling. Here, we identify complete catabolic pathways for the degradation of the common phospholipid headgroups phosphocholine (PC) and phosphorylethanolamine (PE) in marine bacteria.
The carbon footprint of products used in five common surgical operations: identifying contributing products and processes
Chantelle Rizan, Robert Lillywhite, Malcolm Reed, Mahmood F Bhutta
The aim of this study was to evaluate the carbon footprint of products used within five common operations, and to identify the biggest contributors (hotspots). We determined the carbon footprint of the products used in each of the five operations, alongside greatest contributors through analysis of individual products and of underpinning processesAcross the five operations, 23% of product types were responsible for 80% of the operation carbon footprint. Mean average contribution from production of single-use items was 54%, decontamination of reusables 20%, waste disposal of single-use items 8%, production of packaging for single-use items 6% and linen laundering 6%. Change in practice and policy should be targeted towards those products making greatest contribution, and should include reducing single-use items and switching to reusables, alongside optimising processes for decontamination and waste disposal, modelled to reduce carbon footprint of these operations by 23%-42%.
Penicillin Binding Protein Substitutions Cooccur with Fluoroquinolone Resistance in Epidemic Lineages of Multidrug-Resistant Clostridioides difficile
Dingle KE, Freeman J, Didelot X, Quan TP, Eyre DW, Swann J, Spittal WD, Clark EV, Jolley KA, Walker AS, Wilcox MH
Clostridioides difficile remains a key cause of healthcare-associated infection, with multidrug-resistant (MDR) lineages causing high-mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship is a key control. A mechanism underlying raised cephalosporin MICs has not been identified in C. difficile, but among other species, this is often acquired via amino acid substitutions in cell wall transpeptidases (penicillin binding proteins [PBPs]). Here, we investigated five C. difficile transpeptidases (PBP1 to PBP5) for recent substitutions, associated cephalosporin MICs, and co-occurrence with fluoroquinolone resistance. Here, we identify a mechanism associated with raised cephalosporin MICs in C. difficile comprising amino acid substitutions in two cell wall transpeptidase enzymes (penicillin binding proteins). Our study identifies a mechanism that may explain the contribution of cephalosporin stewardship to resolving outbreak conditions. However, due to the co-occurrence of raised cephalosporin MICs and fluoroquinolone resistance, further work is needed to determine the relative importance of each.
Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations
Jessica Brown, Elena Camporesi, Juan Lantero-Rodriguez, Maria Olsson, Alice Wang, Blanca Medem, Henrik Zetterberg, Kaj Blennow, Thomas K. Karikari, Mark Wall and Emily Hill
Alzheimer’s disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input–output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future.
Water flow plays a key role in determining chemical biodegradation in water-sediment systems
Rebecca V. Southwell, Sally L. Hilton, Jonathan M. Pearson, Laurence H. Hand, Gary D. Bending
Before agrochemicals can be registered and sold, the chemical industry is required to perform regulatory tests to assess their environmental persistence, using defined guidelines. Aquatic fate tests (e.g. OECD 308) lack environmental realism as they are conducted under dark conditions and in small-scale static systems, which can affect microbial diversity and functionality. In this study, water-sediment microflumes were used to investigate the impact of these deficiencies in environmental realism on the fate of the fungicide, isopyrazam. We conclude that both water velocity and non-UV light increased isopyrazam dissipation, but the contribution of light depended on the flow conditions. These differences may have resulted from impacts on microbial communities and via mixing processes, particularly hyporheic exchange. Inclusion of both light and flow in studies could improve the extent they mimic natural environments and predict chemical environmental persistence, thus bridging the gap between laboratory and field studies.
Phylogenomic analysis uncover a nine-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains
Grace Nabakooza, D. Collins Owuor, Zaydah R. de Laurent, Ronald Galiwango, Nicholas Owor, John T. Kayiwa, Daudi Jjingo, Charles N. Agoti, D. James Nokes, David P. Kateete, John M. Kitayimbwa, Simon D. W. Frost, Julius J. Lutwama
Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. The newly-generated sequences were genetically and phylogenetically compared to the WHO-recommended vaccines and other Africa strains sampled since 1994. We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017–2019.