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  • Journal article
    Morton R, Singanayagam A, 2022,

    The respiratory tract microbiome: moving from correlation to causation

  • Conference paper
    Blanco JM, Danckert NP, Liu Z, Martinez-Gili L, Mullish BH, McDonald JA, Lindsay M, Sengupta R, McHugh N, Abraham S, Marchesi Jet al., 2022,

    New links between psoriatic arthritis and the gut microbiome suggest a stronger role of the gut-joint axis

    , Digestive Disease Week® (DDW) 2022, Publisher: Elsevier, Pages: S456-S457, ISSN: 0016-5085
  • Journal article
    Paizs P, Mullish BH, Alexander JL, Maneta-Stavrakaki S, Sani M, Ford L, Monaghan T, Kinross JM, McDonald JA, Kao DH, Marchesi J, Takats Zet al., 2022,


    , GASTROENTEROLOGY, Vol: 162, Pages: S649-S649, ISSN: 0016-5085
  • Journal article
    Godlee C, Cerny OE, Liu M, Blundell SW, Gallagher AM, Shahin MM, Holden DMet al., 2022,

    The <i>Salmonella</i> transmembrane effector SteD hijacks AP1-mediated vesicular trafficking for delivery to antigen-loading MHCII compartments

    , PLOS PATHOGENS, Vol: 18, ISSN: 1553-7366
  • Journal article
    Rhodes J, 2022,

    Population genomics confirms acquisition of drug resistant Aspergillus fumigatus infection by humans from the environment

    , Nature Microbiology, Vol: 7, ISSN: 2058-5276

    Infections caused by the fungal pathogen Aspergillus fumigatus are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about how susceptible patients acquire infection from drug resistant genotypes in the environment. Here, we present a population genomic analysis of 218 A. fumigatus from across the United Kingdom and Ireland (comprising 153 clinical isolates from 143 patients, and 65 environmental isolates). First, phylogenomic analysis shows strong genetic structuring into two clades (‘A’ and ‘B’) with little interclade recombination and the majority of environmental azole resistance found within Clade A. Secondly, we show occurrences where azole resistant isolates of near identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Third, genome-scans identified selective sweeps across multiple regions indicating a polygenic basis to the trait in some genetic backgrounds. These signatures of positive selection are seen for loci containing the canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, whilst other regions under selection have no defined function. Lastly, pangenome analysis identified genes linked to azole resistance and novel resistance mechanisms. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.

  • Journal article
    Ledger E, Mesnage S, Edwards A, 2022,

    Human serum triggers antibiotic tolerance in Staphylococcus aureus

    , Nature Communications, Vol: 13, Pages: 1-19, ISSN: 2041-1723

    Staphylococcus aureus frequently causes infections that are challenging to treat, leading to high rates of persistent and relapsing infection. Here, to understand how the host environment influences treatment outcomes, we study the impact of human serum on staphylococcal antibiotic susceptibility. We show that serum triggers a high degree of tolerance to the lipopeptide antibiotic daptomycin and several other classes of antibiotic. Serum-induced daptomycin tolerance is due to two independent mechanisms. Firstly, the host defence peptide LL-37 induces tolerance by triggering the staphylococcal GraRS two-component system, leading to increased peptidoglycan accumulation. Secondly, GraRS-independent increases in membrane cardiolipin abundance are required for full tolerance. When both mechanisms are blocked, S. aureus incubated in serum is as susceptible to daptomycin as when grown in laboratory media. Our work demonstrates that host factors can significantly modulate antibiotic susceptibility via diverse mechanisms, and combination therapy may provide a way to mitigate this.

  • Journal article
    Switzer A, Burchell L, Mitsidis P, Thurston T, Wigneshweraraj Set al., 2022,

    A role for the RNA polymerase gene specificity factor sigma(54) in the uniform colony growth of uropathogenic escherichia coli

    , Journal of Bacteriology, Vol: 204, Pages: 1-16, ISSN: 0021-9193

    The canonical function of a bacterial sigma (σ) factor is to determine the gene specificity of the RNA polymerase (RNAP). In several diverse bacterial species, the σ54 factor uniquely confers distinct functional and regulatory properties on the RNAP. A hallmark feature of the σ54-RNAP is the obligatory requirement for an activator ATPase to allow transcription initiation. Different activator ATPases couple diverse environmental cues to the σ54-RNAP to mediate adaptive changes in gene expression. Hence, the genes that rely upon σ54 for their transcription have a wide range of different functions suggesting that the repertoire of functions performed by genes, directly or indirectly affected by σ54, is not yet exhaustive. By comparing the growth patterns of prototypical enteropathogenic, uropathogenic, and nonpathogenic Escherichia coli strains devoid of σ54, we uncovered that the absence of σ54 results in two differently sized colonies that appear at different times specifically in the uropathogenic E. coli (UPEC) strain. Notably, UPEC bacteria devoid of individual activator ATPases of the σ54-RNAP do not phenocopy the σ54 mutant strain. Thus, it seems that σ54’s role as a determinant of uniform colony appearance in UPEC bacteria represents a putative non-canonical function of σ54 in regulating genetic information flow.

  • Journal article
    Ibarra-Chávez R, Brady A, Chen J, Penadés JR, Haag AFet al., 2022,

    Phage-inducible chromosomal islands promote genetic variability by blocking phage reproduction and protecting transductants from phage lysis

    , PLoS Genetics, Vol: 18, ISSN: 1553-7390

    Phage-inducible chromosomal islands (PICIs) are a widespread family of highly mobile genetic elements that disseminate virulence and toxin genes among bacterial populations. Since their life cycle involves induction by helper phages, they are important players in phage evolution and ecology. PICIs can interfere with the lifecycle of their helper phages at different stages resulting frequently in reduced phage production after infection of a PICI-containing strain. Since phage defense systems have been recently shown to be beneficial for the acquisition of exogenous DNA via horizontal gene transfer, we hypothesized that PICIs could provide a similar benefit to their hosts and tested the impact of PICIs in recipient strains on host cell viability, phage propagation and transfer of genetic material. Here we report an important role for PICIs in bacterial evolution by promoting the survival of phage-mediated transductants of chromosomal or plasmid DNA. The presence of PICIs generates favorable conditions for population diversification and the inheritance of genetic material being transferred, such as antibiotic resistance and virulence genes. Our results show that by interfering with phage reproduction, PICIs can protect the bacterial population from phage attack, increasing the overall survival of the bacterial population as well as the transduced cells. Moreover, our results also demonstrate that PICIs reduce the frequency of lysogenization after temperate phage infection, creating a more genetically diverse bacterial population with increased bet-hedging opportunities to adapt to new niches. In summary, our results identify a new role for the PICIs and highlight them as important drivers of bacterial evolution.

  • Journal article
    Pinto AL, Rai RK, Brown JC, Griffin P, Edgar JR, Shah A, Singanayagam A, Hogg C, Barclay WS, Futter CE, Burgoyne Tet al., 2022,

    Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium

    , Nature Communications, Vol: 13, Pages: 1-14, ISSN: 2041-1723

    Ultrastructural studies of SARS-CoV-2 infected cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Here, we examined human airway epithelium infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Key SARS-CoV-2 entry molecules, ACE2 and TMPRSS2, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistently, extracellular virions were seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion where tomography showed that the viral membrane was continuous with the apical plasma membrane and the nucleocapsids diluted, compared with unfused virus, demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein. Tomography showed concentration of nucleocapsids round the periphery of profiles strongly suggestive of viral budding into these compartments and this may explain how virions gain their S glycoprotein containing envelope.

  • Journal article
    Kreutzberger MAB, Sobe RC, Sauder AB, Chatterjee S, Peña A, Wang F, Giron JA, Kiessling V, Costa TRD, Conticello VP, Frankel G, Kendall MM, Scharf BE, Egelman EHet al., 2022,

    Flagellin outer domain dimerization modulates motility in pathogenic and soil bacteria from viscous environments.

    , Nature Communications, Vol: 13, Pages: 1-13, ISSN: 2041-1723

    Flagellar filaments function as the propellers of the bacterial flagellum and their supercoiling is key to motility. The outer domains on the surface of the filament are non-critical for motility in many bacteria and their structures and functions are not conserved. Here, we show the atomic cryo-electron microscopy structures for flagellar filaments from enterohemorrhagic Escherichia coli O157:H7, enteropathogenic E. coli O127:H6, Achromobacter, and Sinorhizobium meliloti, where the outer domains dimerize or tetramerize to form either a sheath or a screw-like surface. These dimers are formed by 180° rotations of half of the outer domains. The outer domain sheath (ODS) plays a role in bacterial motility by stabilizing an intermediate waveform and prolonging the tumbling of E. coli cells. Bacteria with these ODS and screw-like flagellar filaments are commonly found in soil and human intestinal environments of relatively high viscosity suggesting a role for the dimerization in these environments.

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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