22 results found
Berger CN, Crepin VF, Roumeliotis TI, et al., 2017, Citrobacter rodentium Subverts ATP Flux and Cholesterol Homeostasis in Intestinal Epithelial Cells In Vivo., Cell Metab
The intestinal epithelial cells (IECs) that line the gut form a robust line of defense against ingested pathogens. We investigated the impact of infection with the enteric pathogen Citrobacter rodentium on mouse IEC metabolism using global proteomic and targeted metabolomics and lipidomics. The major signatures of the infection were upregulation of the sugar transporter Sglt4, aerobic glycolysis, and production of phosphocreatine, which mobilizes cytosolic energy. In contrast, biogenesis of mitochondrial cardiolipins, essential for ATP production, was inhibited, which coincided with increased levels of mucosal O2 and a reduction in colon-associated anaerobic commensals. In addition, IECs responded to infection by activating Srebp2 and the cholesterol biosynthetic pathway. Unexpectedly, infected IECs also upregulated the cholesterol efflux proteins AbcA1, AbcG8, and ApoA1, resulting in higher levels of fecal cholesterol and a bloom of Proteobacteria. These results suggest that C. rodentium manipulates host metabolism to evade innate immune responses and establish a favorable gut ecosystem.
Furniss RCD, Clements A, 2017, Regulation of the Locus of Enterocyte Effacement in Attaching and Effacing Pathogens., J Bacteriol
Attaching and Effacing (AE) pathogens colonise the gut mucosa using a Type Three Secretion System (T3SS) and a suite of effector proteins. The Locus of Enterocyte Effacement (LEE) is the defining genetic feature of the AE pathogens, encoding the T3SS and the core effector proteins necessary for pathogenesis. Extensive research has revealed a complex regulatory network that senses and responds to a myriad of host and microbiota-derived signals in the infected gut to control transcription of the LEE. These signals include microbiota-liberated sugars and metabolites in the gut lumen, molecular oxygen at the gut epithelium and host hormones. Recent research has revealed that AE pathogens also perceive physical signals, such as attachment to the epithelium, and that the act of effector translocation remodels gene expression in infecting bacteria. In this review we summarise our knowledge to date and present an integrated view of how chemical, geographical and physical cues regulate the virulence program of AE pathogens during infection.
Furniss RCD, Slater S, Frankel G, et al., 2016, Enterohaemorrhagic E. coli modulates an ARF6:Rab35 signaling axis to prevent recycling endosome maturation during infection, JOURNAL OF MOLECULAR BIOLOGY, Vol: 428, Pages: 3399-3407, ISSN: 0022-2836
Larrouy-Maumus G, Clements A, Filloux A, et al., 2016, Direct detection of lipid A on intact Gram-negative bacteria by MALDI-TOF mass spectrometry, JOURNAL OF MICROBIOLOGICAL METHODS, Vol: 120, Pages: 68-71, ISSN: 0167-7012
Mavridou DAI, Gonzalez D, Clements A, et al., 2016, The pUltra plasmid series: A robust and flexible tool for fluorescent labeling of Enterobacteria, PLASMID, Vol: 87-88, Pages: 65-71, ISSN: 0147-619X
Clements A, Stoneham CA, Furniss RCD, et al., 2014, Enterohaemorrhagic Escherichia coli inhibits recycling endosome function and trafficking of surface receptors, CELLULAR MICROBIOLOGY, Vol: 16, Pages: 1693-1705, ISSN: 1462-5814
Young JC, Clements A, Lang AE, et al., 2014, The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723
Clements A, Berger CN, Lomma M, et al., 2013, Type 3 secretion effectors, Escherichia coliPathotypes and Principles of Pathogenesis, Editors: Donnenberg, ISBN: 978-0-12-397048-0
Raymond B, Young JC, Pallett M, et al., 2013, Subversion of trafficking, apoptosis, and innate immunity by type III secretion system effectors, TRENDS IN MICROBIOLOGY, Vol: 21, Pages: 430-439, ISSN: 0966-842X
Velkov T, Soon RL, Chong PL, et al., 2013, Molecular basis for the increased polymyxin susceptibility of Klebsiella pneumoniae strains with under-acylated lipid A, INNATE IMMUNITY, Vol: 19, Pages: 265-277, ISSN: 1753-4259
Clements A, Young JC, Constantinou N, et al., 2012, Infection strategies of enteric pathogenic Escherichia coli., Gut Microbes, Vol: 3, Pages: 71-87
Enteric Escherichia coli (E. coli) are both natural flora of humans and important pathogens causing significant morbidity and mortality worldwide. Traditionally enteric E. coli have been divided into 6 pathotypes, with further pathotypes often proposed. In this review we suggest expansion of the enteric E. coli into 8 pathotypes to include the emerging pathotypes of adherent invasive E. coli (AIEC) and Shiga-toxin producing enteroaggregative E. coli (STEAEC). The molecular mechanisms that allow enteric E. coli to colonize and cause disease in the human host are examined and for two of the pathotypes that express a type 3 secretion system (T3SS) we discuss the complex interplay between translocated effectors and manipulation of host cell signaling pathways that occurs during infection.
Wong ARC, Clements A, Raymond B, et al., 2012, The Interplay between the Escherichia coli Rho Guanine Nucleotide Exchange Factor Effectors and the Mammalian RhoGEF Inhibitor EspH, MBIO, Vol: 3, ISSN: 2150-7511
Clements A, Smollett K, Lee SF, et al., 2011, EspG of enteropathogenic and enterohemorrhagic E. coli binds the Golgi matrix protein GM130 and disrupts the Golgi structure and function, CELLULAR MICROBIOLOGY, Vol: 13, Pages: 1429-1439, ISSN: 1462-5814
Wilksch JJ, Yang J, Clements A, et al., 2011, MrkH, a Novel c-di-GMP-Dependent Transcriptional Activator, Controls Klebsiella pneumoniae Biofilm Formation by Regulating Type 3 Fimbriae Expression, PLOS PATHOGENS, Vol: 7, ISSN: 1553-7366
Clements A, Bursac D, Gatsos X, et al., 2009, The reducible complexity of a mitochondrial molecular machine, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 106, Pages: 15791-15795, ISSN: 0027-8424
Clements A, Gaboriaud F, Duval JFL, et al., 2008, The Major Surface-Associated Saccharides of Klebsiella pneumoniae Contribute to Host Cell Association, PLOS ONE, Vol: 3, ISSN: 1932-6203
Clements A, Jenney AW, Farn JL, et al., 2008, Targeting subcapsular antigens for prevention of Klebsiella pneumoniae infections, VACCINE, Vol: 26, Pages: 5649-5653, ISSN: 0264-410X
Clements A, Tull D, Jenney AW, et al., 2007, Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 282, Pages: 15569-15577, ISSN: 0021-9258
Carter DM, Miousse IR, Gagnon J-N, et al., 2006, Interactions between TonB from Escherichia coli and the Periplasmic Protein FhuD, Journal of Biological Chemistry, Vol: 281, Pages: 35413-35424, ISSN: 0021-9258
Jenney AW, Clements A, Farn JL, et al., 2006, Seroepidemiology of Klebsiella pneumoniae in an Australian tertiary hospital and its implications for vaccine development, JOURNAL OF CLINICAL MICROBIOLOGY, Vol: 44, Pages: 102-107, ISSN: 0095-1137
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