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• 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
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  • Citations: 14
• 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
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  • Citations: 4
• Journal article
  Thompson GR, Le T, Chindamporn A, Kauffman CA, Alastruey-Izquierdo A, Ampel NM, Andes DR, Armstrong-James D, Ayanlowo O, Baddley JW, Barker BM, Bezerra LL, Buitrago MJ, Chamani-Tabriz L, Chan JFW, Chayakulkeeree M, Cornely OA, Cunwei C, Gangneux J-P, Govender NP, Hagen F, Hedayati MT, Hohl TM, Jouvion G, Kenyon C, Kibbler CC, Klimko N, Kong DCM, Krause R, Lee LL, Meintjes G, Miceli MH, Rath P-M, Spec A, Queiroz-Telles F, Variava E, Verweij PE, Schwartz IS, Pasqualotto ACet al., 2021,

  Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology

  , LANCET INFECTIOUS DISEASES, Vol: 21, Pages: E364-E374, ISSN: 1473-3099
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  • Citations: 60
• Journal article
  Amin H, Ilangovan A, Costa TRD, 2021,

  Architecture of the outer-membrane core complex from a conjugative type IV secretion system.

  , Nat Commun, Vol: 12

  Conjugation is one of the most important processes that bacteria utilize to spread antibiotic resistance genes among bacterial populations. Interbacterial DNA transfer requires a large double membrane-spanning nanomachine called the type 4 secretion system (T4SS) made up of the inner-membrane complex (IMC), the outer-membrane core complex (OMCC) and the conjugative pilus. The iconic F plasmid-encoded T4SS has been central in understanding conjugation for several decades, however atomic details of its structure are not known. Here, we report the structure of a complete conjugative OMCC encoded by the pED208 plasmid from E. coli, solved by cryo-electron microscopy at 3.3 Å resolution. This 2.1 MDa complex has a unique arrangement with two radial concentric rings, each having a different symmetry eventually contributing to remarkable differences in protein stoichiometry and flexibility in comparison to other OMCCs. Our structure suggests that F-OMCC is a highly dynamic complex, with implications for pilus extension and retraction during conjugation.

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• Journal article
  Brady A, Quiles-Puchalt, Gallego del Sol F, Zamora-Caballero S, Felipe-Ruíz A, Val-Calvo J, Meijer WJJ, Marina A, Penades Jet al., 2021,

  The arbitrium system controls prophage induction

  , Current Biology, Vol: 31, Pages: 5037-5045, ISSN: 0960-9822

  Some Bacillus-infecting bacteriophages use a peptide-based communication system, termed arbitrium, to coordinate the lysis-lysogeny decision. In this system the phage produces AimP peptide during the lytic cycle. Once internalised by the host cell, AimP binds to the transcription factor AimR, reducing aimX expression and promoting lysogeny. Although these systems are present in a variety of mobile genetic elements, their role in the phage life cycle has only been characterised in phage phi3T during phage infection. Here, using the B. subtilis SPb prophage, we show that the arbitrium system is also required for normal prophage induction. Deletion of the aimP gene increased phage reproduction, while the aimR deletion significantly reduced the number of phage particles produced after prophage induction. Moreover, our results indicated that AimR is involved in a complex network of regulation and brought forward two new players in the SPb lysis-lysogeny decision system, YopN and the phage repressor YopR. Importantly, these proteins are encoded in an operon, the function of which is conserved across all SPb-like phages encoding the arbitrium system. Finally, we obtained mutant phages in the arbitrium system, which behaved almost identically to the wt phage, indicating that the arbitrium system is not essential in the laboratory but is likely beneficial for phage fitness in nature. In support of this, by possessing a functional arbitrium system the SPb phage can optimise production of infective particles whilst also preserving the number of cells that survive after prophage induction, a strategy that increases phage persistence in nature.

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• Journal article
  Monaghan TM, Duggal NA, Rosati E, Griffin R, Hughes J, Roach B, Yang DY, Wang C, Wong K, Saxinger L, Pučić-Baković M, Vučković F, Klicek F, Lauc G, Tighe P, Mullish BH, Miguens Blanco J, McDonald JAK, Marchesi JR, Xue N, Dottorini T, Acharjee A, Franke A, Wong GK-S, Polytarchou C, Yau TO, Christodoulou N, Hatziapostoulou M, Wang M, Russell LA, Kao DHet al., 2021,

  A multi-factorial observational study on sequential fecal microbiota transplant in patients with medically refractory Clostridioides difficile infection

  , Cells, Vol: 10, ISSN: 2073-4409

  Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.

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• Journal article
  Fillol-Salom A, Bacigalupe R, Humphrey S, Chiang YN, Chen J, Penades Jet al., 2021,

  Lateral transduction is inherent to the life cycle of the archetypical Salmonella phage P22

  , Nature Communications, Vol: 12, Pages: 1-11, ISSN: 2041-1723

  Lysogenic induction ends the stable association between a bacteriophage and its host, andthe transition to the lytic cycle begins with early prophage excision followed by DNA replication and packaging (ERP). This temporal program is considered universal for P22-liketemperate phages, though there is no direct evidence to support the timing and sequence ofthese events. Here we report that the long-standing ERP program is an observation of theexperimentally favored Salmonella phage P22 tsc229 heat-inducible mutant, and that wildtype P22 actually follows the replication-packaging-excision (RPE) program. We find that P22tsc229 excises early after induction, but P22 delays excision to just before it is detrimental tophage production. This allows P22 to engage in lateral transduction. Thus, at minimalexpense to itself, P22 has tuned the timing of excision to balance propagation with lateraltransduction, powering the evolution of its host through gene transfer in the interest of selfpreservation.

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• Journal article
  Humphrey S, Fillol-Salom A, Quiles-Puchalt N, Ibarra-Chávez R, Haag A, Chen J, Penades Jet al., 2021,

  Bacterial chromosomal mobility via lateral transduction exceeds that of classical mobile genetic elements

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

  It is commonly assumed that the horizontal transfer of most bacterial chromosomal genes is limited, in contrast to the frequent transfer observed for typical mobile genetic elements. However, this view has been recently challenged by the discovery of lateral transduction in Staphylococcus aureus, where temperate phages can drive the transfer of large chromosomalregions at extremely high frequencies. Here, we analyse previously published as well as new datasets to compare horizontal gene transfer rates mediated by different mechanisms in S. aureus and Salmonella enterica. We find that the horizontal transfer of core chromosomal genes via lateral transduction can be more efficient than the transfer of classical mobile genetic elements via conjugation or generalized transduction. These results raise questions about our definition of mobile genetic elements, and the potential roles played by lateral transduction in bacterial evolution.

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• 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 β-clamp inhibitor by occupying the DNA sliding channel

  , NUCLEIC ACIDS RESEARCH, Vol: 49, Pages: 11367-11378, ISSN: 0305-1048
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  • Citations: 4
• Journal article
  Hawkins NC, Kizziah JL, Penades JR, Dokland Tet al., 2021,

  Shape shifter: redirection of prolate phage capsid assembly by staphylococcal pathogenicity islands

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

  Staphylococcus aureus pathogenicity islands (SaPIs) are molecular parasites that hijack helper phages for their transfer. SaPIbov5, the prototypical member of a family of cos type SaPIs, redirects the assembly of ϕ12 helper capsids from prolate to isometric. This size and shape shift is dependent on the SaPIbov5-encoded protein Ccm, a homolog of the ϕ12 capsid protein (CP). Using cryo-electron microscopy, we have determined structures of prolate ϕ12 procapsids and isometric SaPIbov5 procapsids. ϕ12 procapsids have icosahedral end caps with Tend = 4 architecture and a Tmid = 14 cylindrical midsection, whereas SaPIbov5 procapsids have T = 4 icosahedral architecture. We built atomic models for CP and Ccm, and show that Ccm occupies the pentameric capsomers in the isometric SaPIbov5 procapsids, suggesting that preferential incorporation of Ccm pentamers prevents the cylindrical midsection from forming. Our results highlight that pirate elements have evolved diverse mechanisms to suppress phage multiplication, including the acquisition of phage capsid protein homologs.

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