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  • Journal article
    Pruski P, Dos Santos Correia G, Lewis H, Capuccini K, Inglese P, Chan D, Brown R, Kindinger L, Lee Y, Smith A, Marchesi J, McDonald J, Cameron S, Alexander-Hardiman K, David A, Stock S, Norman J, Terzidou V, Teoh TG, Sykes L, Bennett P, Takats Z, MacIntyre Det al., 2021,

    Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth

    , Nature Communications, Vol: 12, ISSN: 2041-1723

    The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.
  • Journal article
    Liu B, Li S, Liu Y, Chen H, Hu Z, Wang Z, Zhao Y, Zhang L, Ma B, Wang H, Matthews S, Wang Y, Zhang Ket al., 2021,

    Bacteriophage Twort protein Gp168 is a beta-clamp inhibitor by occupying the DNA sliding channel

    , NUCLEIC ACIDS RESEARCH, Vol: 49, Pages: 11367-11378, ISSN: 0305-1048
  • Journal article
    Humphrey S, San Millan A, Toll-Riera M, Connolly J, Flor-Duro A, Chen J, Ubeda C, MacLean RC, Penades Jet al., 2021,

    Staphylococcal phages and pathogenicity islands drive plasmid evolution

    , Nature Communications, Vol: 12, Pages: 1-15, ISSN: 2041-1723

    Conjugation has classically been considered the main mechanism driving plasmid transfer in nature. Yet bacteria frequently carry so-called non-transmissible plasmids, raising questions about how these plasmids spread. Interestingly, the size of many mobilizable and non transmissible plasmids coincides with the average size of phages (~40kb) or that of a family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs, ~11 kb). Here, we show that phages and PICIs from Staphylococcus aureus can mediate intra- and inter-species plasmid transfer via generalised transduction, potentially contributing to non-transmissible plasmid spread in nature. Further, staphylococcal PICIs enhance plasmid packaging efficiency, and phages and PICIs exert selective pressures on plasmids via the physical capacity of their capsids, explaining the bimodal size distribution observed for non-conjugative plasmids. Our results highlight that transducing agents (phages, PICIs) have important roles in bacterial plasmid evolution and, potentially, in antimicrobial resistance transmission.
  • Journal article
    Mullineaux Sanders C, Carson D, Hopkins E, Glegola-Madejska I, Escobar-Zepeda A, Browne H, Lawley T, Frankel Get al., 2021,

    Citrobacter amalonaticus inhibits the growth of Citrobacter rodentium in the gut lumen

    , mBio, Vol: 5, Pages: 1-19, ISSN: 2150-7511

    The gut microbiota plays a crucial role in susceptibility to enteric pathogens, including Citrobacter rodentium, a model extracellular mouse pathogen that colonizes the colonic mucosa. C. rodentium infection outcomes vary between mouse strains, with C57BL/6 and C3H/HeN mice clearing or succumbing to the infection respectively. Kanamycin (Kan) treatment at the peak of C57BL/6 mouse infection with Kan-resistant C. rodentium resulted in re-localisation of the pathogen from the colonic mucosa and cecum to solely the cecal luminal contents; cessation of the Kan treatment resulted in rapid clearance of the pathogen. We now show that in C3H/HeN mice, following Kan-induced displacement of C. rodentium to the cecum, the pathogen stably colonizes the cecal lumen of 65% of the mice in the absence of continued antibiotic treatment, a phenomenon we term antibiotic-induced bacterial commensalisation (AIBC). AIBC C. rodentium was well-tolerated by the host, which showed little signs of inflammation; passaged AIBC C. rodentium robustly infected naïve C3H/HeN mice suggesting that the AIBC state is transient and did not select for genetically avirulent C. rodentium mutants. Following withdrawal of antibiotic treatment, 35% of C3H/HeN mice were able to prevent C. rodentium commensalisation in the gut lumen. These mice presented a bloom of a commensal species, Citrobacter amalonaticus, which inhibited the growth of C. rodentium in vitro in a contact-dependant manner, and luminal growth of AIBC C. rodentium in vivo. Overall our data suggest that commensal species can confer colonization resistance against closely-related pathogenic species.
  • Journal article
    Mincham KT, Bruno N, Singanayagam A, Snelgrove RJet al., 2021,

    Our evolving view of neutrophils in defining the pathology of chronic lung disease

    , IMMUNOLOGY, Vol: 164, Pages: 701-721, ISSN: 0019-2805
  • Journal article
    Lee WWY, Mattock J, Greig DR, Langridge GC, Baker D, Bloomfield S, Mather AE, Wain JR, Edwards AM, Hartman H, Dallman TJ, Chattaway MA, Nair Set al., 2021,

    Characterization of a pESI- like plasmid and analysis of multidrug-resistant Salmonella enterica Infantis isolates in England and Wales

    , Microbial Genomics, Vol: 7, Pages: 1-11, ISSN: 2057-5858

    Salmonella enterica serovar Infantis is the fifth most common Salmonella serovar isolated in England and Wales. Epidemiological, genotyping and antimicrobial-resistance data for S. enterica Infantis isolates were used to analyse English and Welsh demographics over a 5 year period. Travel cases associated with S. enterica Infantis were mainly from Asia, followed by cases from Europe and North America. Since 2000, increasing numbers of S. enterica Infantis had multidrug resistance determinants harboured on a large plasmid termed ‘plasmid of emerging S. enterica Infantis’ (pESI). Between 2013 and 2018, 42 S. enterica Infantis isolates were isolated from humans and food that harboured resistance determinants to multiple antimicrobial classes present on a pESI-like plasmid, including extended-spectrum β-lactamases (ESBLs; blaCTX-M-65). Nanopore sequencing of an ESBL-producing human S. enterica Infantis isolate indicated the presence of two regions on an IncFIB pESI-like plasmid harbouring multiple resistance genes. Phylogenetic analysis of the English and Welsh S. enterica Infantis population indicated that the majority of multidrug-resistant isolates harbouring the pESI-like plasmid belonged to a single clade maintained within the population. The blaCTX-M-65 ESBL isolates first isolated in 2013 comprise a lineage within this clade, which was mainly associated with South America. Our data, therefore, show the emergence of a stable resistant clone that has been in circulation for some time in the human population in England and Wales, highlighting the necessity of monitoring resistance in this serovar.
  • Journal article
    Periselneris J, Schelenz S, Loebinger M, Macedo P, Adhya Z, Armstrong-James D, Kelleher WPet al., 2021,

    Bronchiectasis severity correlates with outcome in patients with primary antibody deficiency

    , THORAX, Vol: 76, Pages: 1036-1039, ISSN: 0040-6376
  • Journal article
    Armstrong-James D, 2021,

    Future Directions for Clinical Respiratory Fungal Research.

    , Mycopathologia, Vol: 186, Pages: 685-696

    There has been a growing appreciation of the importance of respiratory fungal diseases in recent years, with better understanding of their prevalence as well as their global distribution. In step with the greater awareness of these complex infections, we are currently poised to make major advances in the characterization and treatment of these fungal diseases, which in itself is largely a consequence of post-genomic technologies which have enabled rational drug development and a path towards personalized medicines. These advances are set against a backdrop of globalization and anthropogenic change, which have impacted the world-wide distribution of fungi and antifungal resistance, as well as our built environment. The current revolution in immunomodulatory therapies has led to a rapidly evolving population at-risk for respiratory fungal disease. Whilst challenges are considerable, perhaps the tools we now have to manage these infections are up to this challenge. There has been a welcome acceleration of the antifungal pipeline in recent years, with a number of new drug classes in clinical or pre-clinical development, as well as new focus on inhaled antifungal drug delivery. The "post-genomic" revolution has opened up metagenomic diagnostic approaches spanning host immunogenetics to the fungal mycobiome that have allowed better characterization of respiratory fungal disease endotypes. When these advances are considered together the key challenge is clear: to develop a personalized medicine framework to enable a rational therapeutic approach.
  • Journal article
    Grabe GJ, Giorgio RT, Hall AMJ, Morgan RML, Dubois L, Sisley TA, Rycroft JA, Hare SA, Helaine Set al., 2021,

    Auxiliary interfaces support the evolution of specific toxin-antitoxin pairing

    , NATURE CHEMICAL BIOLOGY, Vol: 17, Pages: 1296-1304, ISSN: 1552-4450
  • Journal article
    Rose S, Beckwith EJ, Burmester C, May RC, Dionne MS, Rezaval Cet al., 2021,

    Pre-copulatory reproductive behaviours are preserved in <i>Drosophila melanogaster</i> infected with bacteria

    <jats:title>Abstract</jats:title><jats:p>Reproduction and immunity are crucial traits that determine an animal’s fitness. Terminal investment hypothesis predicts that reproductive investment should increase in the face of a mortality risk caused by infection. However, due to competitive allocation of energetic resources, individuals fighting infections are expected to decrease reproductive efforts. While there is evidence for both hypotheses, the factors that determine the choice between these strategies are poorly understood. Here, we assess the impact of bacterial infection on pre-copulatory behaviours in the fruit fly <jats:italic>Drosophila melanogaster</jats:italic>. We found that male flies infected with six different bacteria, including pathogenic and non-pathogenic strains, show no significant differences in courtship intensity and mating success. Similarly, bacterial infections did not affect sexual receptivity in female flies. Our data suggest that pre-copulatory reproductive behaviours remain preserved in infected animals, despite the huge metabolic cost of infection.</jats:p>

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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