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  • Journal article
    Singanayagam A, Footitt J, Marczynski M, Radicioni G, Cross MT, Finney LJ, Trujillo-Torralbo M-B, Calderazzo MA, Zhu J, Aniscenko J, Clarke TB, Molyneaux PL, Bartlett NW, Moffatt MF, Cookson WO, Wedzicha JA, Evans CM, Boucher RC, Kesimer M, Lieleg O, Mallia P, Johnston SLet al., 2022,

    Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease.

    , Journal of Clinical Investigation, Vol: 132, Pages: 1-16, ISSN: 0021-9738

    The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway MUC5AC and MUC5B concentrations during spontaneous and experimentally-induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with virus load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation as Muc5ac-deficient (Muc5ac-/-) mice had attenuated rhinovirus (RV)-induced airway inflammation and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of rhinovirus-induced inflammation in mice. Therapeutic suppression of mucin production using an epidermal growth factor receptor (EGFR) antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identifies a pro-inflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.

  • Journal article
    Xu X, Marffy ALL, Keightley A, McCarthy AJ, Geisbrecht Bet al., 2022,

    Group B <i>Streptococcus</i> Surface Protein β: Structural Characterization of a Complement Factor H-Binding Motif and Its Contribution to Immune Evasion

    , JOURNAL OF IMMUNOLOGY, Vol: 208, Pages: 1232-1247, ISSN: 0022-1767
  • Conference paper
    MacIntyre DA, Pruski P, Correia G, Lewis H, Capuccini K, Inglese P, Chan D, Brown R, Kindinger L, Lee YS, Smith A, Marchesi J, McDonald J, Cameron S, Alexander-Hardiman K, David A, Stock S, Norman J, Terzidou V, Teoh TG, Sykes L, Bennett PR, Takats Zet al., 2022,

    Rapid Assessment of Vaginal Microbiota Host Interactions During Pregnancy and Preterm Birth by Direct On-Swab Desorption Electrospray Ionization Mass Spectrometry

    , Publisher: SPRINGER HEIDELBERG, Pages: 53-53, ISSN: 1933-7191
  • Journal article
    Marshall EKP, Dionne MS, 2022,

    Drosophila versus Mycobacteria: A model for mycobacterial host-pathogen interactions

    , MOLECULAR MICROBIOLOGY, Vol: 117, Pages: 600-609, ISSN: 0950-382X
  • Journal article
    Serafini N, Jarade A, Surace L, Goncalves P, Sismeiro O, Varet H, Legendre R, Coppee J-Y, Disson O, Durum SK, Frankel G, Di Santo JPet al., 2022,

    Trained ILC3 responses promote intestinal defense

    , SCIENCE, Vol: 375, Pages: 859-+, ISSN: 0036-8075
  • Journal article
    Nuh A, Ramadan N, Shah A, Armstrong-James Det al., 2022,

    Sputum galactomannan has utility in the diagnosis of chronic pulmonary aspergillosis

    , Journal of Fungi, Vol: 8, Pages: 1-10, ISSN: 2309-608X

    Diagnosis of pulmonary aspergillosis (PA), a fungal disease caused by Aspergillus species, is challenging since symptoms are unspecific. The galactomannan (antigen secreted by Aspergillus species) test in bronchoalveolar lavage (BAL) fluid is a valuable diagnostic adjunct test in the diagnosis of PA. However, BAL collection is invasive and may not be suitable to severely ill patients. Sputum is non-invasive, easily collected, and lung specific and may be an alternative to BAL. The aim of this research was to retrospectively evaluate the utility of sputum galactomannan in the diagnosis of pulmonary aspergillosis in patients with chronic respiratory diseases and to estimate the sputum galactomannan cut-off value. We collected data from patients with clinical suspicion of pulmonary aspergillosis who had sputum galactomannan, culture, and Aspergillus IgG tests performed within four weeks. Sputum galactomannan was validated against the clinical diagnosis of aspergillosis, Aspergillus culture, and Aspergillus IgG tests. In total, 218 patients met inclusion criteria. Overall, sputum GM showed satisfactory agreement with clinical diagnosis of aspergillosis, Aspergillus culture, and Aspergillus IgG. When a receiver operating characteristic curve was constructed using Aspergillus culture/IgG and clinical diagnosis, the same cut-off (CO) of 0.71 (AUC: 0.83; CI: 0.69–0.86, p < 0.001) was determined. Against clinical diagnosis, sputum GM gave sensitivity and specificity of 70% and 71%, respectively. Sensitivity of 77% and specificity of 78% were found when sputum GM was evaluated against Aspergillus culture/IgG. In conclusion, this study showed that sputum galactomannan antigen testing has utility in the diagnosis of chronic forms of pulmonary aspergillosis and further prospective validation is indicated.

  • Conference paper
    Kreutzberger MA, Sobe R, Sauder AB, Chatterjee S, Wang F, Kiessling V, Conticello V, Frankel G, Kendall M, Scharf B, Egelman EHet al., 2022,

    Cryo-EM of bacterial flagellar filaments with screw-like surfaces and outer domain sheaths

    , Publisher: CELL PRESS, Pages: 131-131, ISSN: 0006-3495
  • Journal article
    Mullineaux Sanders C, Kozik Z, Sanchez Garrido J, Hopkins EGD, Choudhary JS, Frankel Get al., 2022,

    Citrobacter rodentium infection induces persistent molecular changes and interferon gamma-dependent major histocompatibility complex class II expression in the colonic epithelium

    , mBio, Vol: 13, Pages: 1-18, ISSN: 2150-7511

    Most studies of infections at mucosal surfaces have focused on the acute phase of the disease. Consequently, little is known about the molecular processes that underpin tissue recovery and the long-term consequences postinfection. Here, we conducted temporal deep quantitative proteomic analysis of colonic intestinal epithelial cells (cIECs) from mice infected with the natural mouse pathogen Citrobacter rodentium over time points corresponding to the late steady-state phase (10 days postinfection [DPI]), the clearance phase (13 to 20 DPI), and 4 weeks after the pathogen has been cleared (48 DPI). C. rodentium, which relies on a type III secretion system to infect, is used to model infections with enteropathogenic and enterohemorrhagic Escherichia coli. We observe a strong upregulation of inflammatory signaling and nutritional immunity responses during the clearance phase of the infection. Despite morphological tissue recovery, chromogranin B (ChgB)-positive endocrine cells remained significantly below baseline levels at 48 DPI. In contrast, we observed an increased abundance of proteins involved in antigen processing and presentation 4 weeks after pathogen clearance. In particular, long-term changes were characterized by a persistent interferon gamma (IFN-γ) response and the expression of major histocompatibility complex class II (MHCII) molecules in 60% of the EpCAM+ cIECs, which were not seen in Ifnγ−/− mice. Nonetheless, both wild-type and Ifnγ−/− mice mounted similar systemic and colonic IgG responses to C. rodentium and were equally protected from rechallenge, suggesting that cIEC MHCII is not necessary for protective immunity against C. rodentium.

  • Journal article
    Ledger EVK, Sabnis A, Edwards AM, 2022,

    Polymyxin and lipopeptide antibiotics: membrane- targeting drugs of last resort

    , Microbiology, Vol: 168, Pages: 1-20, ISSN: 1350-0872

    The polymyxin and lipopeptide classes of antibiotics are membrane-targeting drugs of last resort used to treat infections caused by multi-drug-resistant pathogens. Despite similar structures, these two antibiotic classes have distinct modes of action and clinical uses. The polymyxins target lipopolysaccharide in the membranes of most Gram-negative species and are often used to treat infections caused by carbapenem-resistant species such as Escherichia coli , Acinetobacter baumannii and Pseudomonas aeruginosa . By contrast, the lipopeptide daptomycin requires membrane phosphatidylglycerol for activity and is only used to treat infections caused by drug-resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. However, despite having distinct targets, both antibiotic classes cause membrane disruption, are potently bactericidal in vitro and share similarities in resistance mechanisms. Furthermore, there are concerns about the efficacy of these antibiotics, and there is increasing interest in using both polymyxins and daptomycin in combination therapies to improve patient outcomes. In this review article, we will explore what is known about these distinct but structurally similar classes of antibiotics, discuss recent advances in the field and highlight remaining gaps in our knowledge.

  • Journal article
    Sperandio V, Frankel G, 2022,

    Editorial overview: Host-microbe interactions: friends, foes and frenemies

    , CURRENT OPINION IN MICROBIOLOGY, Vol: 65, Pages: VIII-X, ISSN: 1369-5274

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