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Liver sinusoidal cells eliminate blood-borne phage K1F

Javier Sánchez Romano, Jaione Simón-Santamaria, Peter McCourt, Bård Smedsrød, Kim Erlend Mortensen, Antonia P. Sagona, Karen Kristine Sørensen, Anett Kristin Larsen

Blood-borne phages are believed to be captured by macrophages in the liver and spleen. Since liver sinusoids also consist of specialized scavenger liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), this study investigated the contribution of both cell types in the elimination of Escherichia coli phage K1Fg10b::gfp (K1Fgfp) in mice. The results presented herein contribute to increased knowledge about the pharmacokinetics of the T7-like phage K1F in the mammalian system. The cell types of the liver that are responsible for rapid phage blood clearance are identified. Our results highlight the need for more research about appropriate dose regimens when phage therapy is delivered intravenously and advise essential knowledge about cell systems that should be investigated further for detailed phage pharmacodynamics.

mSphere. February 2024


First archaeological evidence for ginger consumption as a potential medicinal ingredient in a late medieval leprosarium at St Leonard, Peterborough, England

Elena Fiorin, Charlotte A. Roberts, Marica Baldoni, Erin Connelly, Christina Lee, Claudio Ottoni & Emanuela Cristiani

Leprosy was one of the most outwardly visible diseases in the European Middle Ages, a period during which leprosaria were founded to provide space for the sick. In the present study, microremains and DNA were analysed from the calculus of individuals buried in the late medieval cemetery of St Leonard, a leprosarium located in Peterborough, England. The results show the presence of ginger (Zingiber officinale), a culinary and medicinal ingredient, as well as evidence of consumption of cereals and legumes. This research suggests that affected individuals consumed ingredients mentioned in medieval medical textbooks that were used to treat regions of the body typically impacted by leprosy. To the authors' knowledge, this is the first study which has identified Zingiber officinale in human dental calculus in England or on the wider European continent.

Scientific Reports. January 2024

Thu 29 Feb 2024, 08:11 | Tags: Microbiology & Infectious Disease

Genetic manipulation of Indian mustard genotypes with WRR-gene(s) confers resistance against Albugo candida

Nirwan, Shradha, Chatterjee, Anupriya, Cevik, Volkan, Holub, Eric B., Jones, Jonathan D. G., Tewari, Anand Kumar, Shrivastava, Neeraj, Agnihotri, Abha and Sharma, Pankaj

In an effort to develop resistant plants, Agrobacterium mediated genetic transformation of three B. juncea genotypes viz., susceptible host var. Varuna, along with its doubled haploid mutant lines C66 and C69 (showing moderate tolerance to field isolates of A. candida) was initiated to transfer resistance genes (WRR8Sf-2 and WRR9Hi-0) identified in Arabidopsis thaliana against race Ac2V, that encode for Toll-like/interleukin-1 receptor-nucleotide binding-leucine-rich repeat proteins that recognize effectors of the pathogen races. Our results demonstrate that introduction of resistance genes from a tertiary gene pool by genetic transformation enhances disease resistance in B. juncea genotypes to a highly virulent Ac2V isolate.

Molecular Biology Reports. January 2024

Mon 26 Feb 2024, 08:11 | Tags: Plant & Agricultural Bioscience

Xavier Didelot publications

Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes

Y Wan, AC Myall, A Boonyasiri, F Bolt, A Ledda, S Mookerjee, AY Weiße, M Getino, JF Turton, H Abbas, R Prakapaite, A Sabnis, A Abdolrasouli, K Malpartida-Cardenas, L Miglietta, H Donaldson, M Gilchrist, KL Hopkins, MJ Ellington, JA Otter, G Larrouy-Maumus, M Edwards, J Rodriguez-Manzano, X Didelot, M Barahona, AH Holmes, E Jauneikaite, F Davies

Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. Our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.

Journal of Infectious Diseases. January 2024

Genomic epidemiology of the clinically dominant clonal complex 1 in the Listeria monocytogenes population in the UK

Emily T. Fotopoulou​, Claire Jenkins, Clare R. Barker​, Anais Painset​, Xavier Didelot​, Ameze Simbo​, Amy Douglas​, Gauri Godbole​, Frieda Jorgensen​, Saheer Gharbia​, Jim McLauchlin

Listeria monocytogenes is a food-borne pathogen, typically affecting the elderly, immunocompromised patients and pregnant women. The aim of this study was to determine the population structure of L. monocytogenes clonal complex 1 (CC1) in the UK and describe the genomic epidemiology of this clinically significant CC. We interrogated a working dataset of 4073 sequences of L. monocytogenes isolated between January 2015 and December 2020 from human clinical specimens, food and/or foodproduction environments. Analysis of demographic and clinical outcome data identified CC1 as a clinically significant cause of invasive listeriosis in the elderly population and in women of child-bearing age. Phylogenetic analysis revealed the population structure of CC1 in the UK comprised small, sparsely populated genomic clusters. Only clusters containing isolates from an implicated food vehicle, or food processing or farming environments, were resolved, emphasizing the need for clinical, food and animal-health agencies to share sequencing data in real time, and the importance of a One Health approach to public-health surveillance of listeriosis.

Microbial Genomics. January 2024

Thu 22 Feb 2024, 08:28 | Tags: Microbiology & Infectious Disease

Temporal changes in the positivity rate of common enteric viruses among paediatric admissions in coastal Kenya, during the COVID-19 pandemic, 2019-2022

Arnold W. Lambisia, Nickson Murunga, Martin Mutunga, Robinson Cheruiyot, Grace Maina, Timothy O. Makori, D. James Nokes and Charles N. Agoti

The non-pharmaceutical interventions (NPIs) implemented to curb the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic, substantially disrupted the activity of other respiratory viruses. However, there is limited data from low-and-middle income countries (LMICs) to determine whether these NPIs also impacted the transmission of common enteric viruses. Here, we investigated the changes in the positivity rate of five enteric viruses among hospitalised children who presented with diarrhoea to a referral hospital in coastal Kenya, during COVID-19 pandemic period. Our study finds that in 2020 the transmission of common enteric viruses, especially RVA and astrovirus, in Kilifi Kenya may have been disrupted due to the COVID-19 NPIs. After 2020, local enteric virus transmission patterns appeared to return to pre-pandemic levels coinciding with the removal of most of the government COVID-19 NPIs.

Gut Pathogens. January 2024

Mon 19 Feb 2024, 08:28 | Tags: Microbiology & Infectious Disease

Slow release of a synthetic auxin induces formation of adventitious roots in recalcitrant woody plants

O Roth, S Yechezkel, O Serero, A Eliyahu, I Vints, P Tzeela, A Carignano, DP Janacek, V Peters, A Kessel, V Dwivedi, M Carmeli-Weissberg, F Shaya, i Faigenboim-Doron, KL Ung, B Panyella Pedersen, J Riov, E Klavins, C Dawid, Z Hammes, N Ben-Tal, R Napier, E Sadot, R Weinstain

Clonal propagation of plants by induction of adventitious roots (ARs) from stem cuttings is a requisite step in breeding programs. Due to the central role of auxin in organogenesis, indole-3-butyric acid is often used as part of commercial rooting mixtures, yet many recalcitrant plants do not form ARs in response to this treatment. Here we describe the synthesis and screening of a focused library of synthetic auxin conjugates in Eucalyptus grandis cuttings and identify 4-chlorophenoxyacetic acid-L-tryptophan-OMe as a competent enhancer of adventitious rooting in a number of recalcitrant woody plants, including apple and argan. Comprehensive metabolic and functional analyses reveal that this activity is engendered by prolonged auxin signaling due to initial fast uptake and slow release and clearance of the free auxin 4-chlorophenoxyacetic acid. This work highlights the utility of a slow-release strategy for bioactive compounds for more effective plant growth regulation.

Nature Biotechnology. January 2024

Thu 15 Feb 2024, 08:18 | Tags: Plant & Agricultural Bioscience

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