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  • Journal article
    Nicod SS, Weinzierl RO, Burchell L, Escalera-Maurer A, James EH, Wigneshweraraj Set al., 2014,

    Systematic mutational analysis of the LytTR DNA binding domain of Staphylococcus aureus virulence gene transcription factor AgrA

    , Nucleic Acids Research, Vol: 42, Pages: 12523-12536, ISSN: 1362-4962

    Most DNA-binding bacterial transcription factors contact DNA through a recognition α-helix in their DNA-binding domains. An emerging class of DNA-binding transcription factors, predominantly found in pathogenic bacteria interact with the DNA via a relatively novel type of DNA-binding domain, called the LytTR domain, which mainly comprises β strands. Even though the crystal structure of the LytTR domain of the virulence gene transcription factor AgrA from Staphylococcus aureus bound to its cognate DNA sequence is available, the contribution of specific amino acid residues in the LytTR domain of AgrA to transcription activation remains elusive. Here, for the first time, we have systematically investigated the role of amino acid residues in transcription activation in a LytTR domain-containing transcription factor. Our analysis, which involves in vivo and in vitro analyses and molecular dynamics simulations of S. aureus AgrA identifies a highly conserved tyrosine residue, Y229, as a major amino acid determinant for maximal activation of transcription by AgrA and provides novel insights into structure-function relationships in S. aureus AgrA.
  • Journal article
    Campeotto I, Percy MG, MacDonald JT, Foerster A, Freemont PS, Gruendling Aet al., 2014,

    Structural and Mechanistic Insight into the Listeria monocytogenes Two-enzyme Lipoteichoic Acid Synthesis System

    , Journal of Biological Chemistry, Vol: 289, Pages: 28054-28069, ISSN: 0021-9258

    Lipoteichoic acid (LTA) is an important cell wall componentrequired for proper cell growth in many Gram-positive bacteria.In Listeria monocytogenes, two enzymes are required for the synthesisof this polyglycerolphosphate polymer. The LTA primaseLtaPLm initiates LTA synthesis by transferring the first glycerolphosphate(GroP) subunit onto the glycolipid anchor and theLTA synthase LtaSLm extends the polymer by the repeated additionof GroP subunits to the tip of the growing chain. Here, wepresent the crystal structures of the enzymatic domains ofLtaPLm and LtaSLm. Although the enzymes share the same fold,substantial differences in the cavity of the catalytic site andsurface charge distribution contribute to enzyme specialization.The eLtaSLm structure was also determined in complexwith GroP revealing a second GroP binding site. Mutationalanalysis confirmed an essential function for this binding siteand allowed us to propose a model for the binding of thegrowing chain.
  • Journal article
    Painter KL, Krishna A, Wigneshweraraj S, Edwards AMet al., 2014,

    What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

    , Trends in Microbiology, Vol: In Press, ISSN: 0966-842X
  • Journal article
    Belardinelli JM, Larrouy-Maumus G, Jones V, de Carvalho LPS, McNeil MR, Jackson Met al., 2014,

    Biosynthesis and Translocation of Unsulfated Acyltrehaloses in Mycobacterium tuberculosis

    , Journal of Biological Chemistry, Vol: 289, Pages: 27952-27965, ISSN: 1083-351X
  • Journal article
    Colas C, Menezes S, Gutierrez-Martinez E, Pean CB, Dionne MS, Guermonprez Pet al., 2014,

    An improved flow cytometry assay to monitor phagosome acidification

    , JOURNAL OF IMMUNOLOGICAL METHODS, Vol: 412, Pages: 1-13, ISSN: 0022-1759
  • Journal article
    Collins JW, Chervaux C, Raymond B, Derrien M, Brazeilles R, Kosta A, Chambaud I, Crepin VF, Frankel Get al., 2014,

    Fermented Dairy Products Modulate Citrobacter rodentium-Induced Colonic Hyperplasia

    , JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: 1029-1041, ISSN: 0022-1899
  • Journal article
    Moscoso JA, Jaeger T, Valentini M, Hui K, Jenal U, Filloux Aet al., 2014,

    The Diguanylate Cyclase SadC Is a Central Player in Gac/Rsm-Mediated Biofilm Formation in Pseudomonas aeruginosa

    , Journal of Bacteriology, Vol: 196, Pages: 4081-4088, ISSN: 1098-5530

    Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen and a threat for immunocompromised and cysticfibrosis patients. It is responsible for acute and chronic infections and can switch between these lifestyles upon taking an informeddecision involving complex regulatory networks. The RetS/LadS/Gac/Rsm network and the cyclic-di-GMP (c-di-GMP)signaling pathways are both central to this phenomenon redirecting the P. aeruginosa population toward a biofilm mode ofgrowth, which is associated with chronic infections. While these two pathways were traditionally studied independently fromeach other, we recently showed that cellular levels of c-di-GMP are increased in the hyperbiofilm retS mutant. Here, we have formallyestablished the link between the two networks by showing that the SadC diguanylate cyclase is central to the Gac/Rsmassociatedphenotypes, notably, biofilm formation. Importantly, SadC is involved in the signaling that converges onto the RsmAtranslational repressor either via RetS/LadS or via HptB/HsbR. Although the level of expression of the sadC gene does not seemto be impacted by the regulatory cascade, the production of the SadC protein is tightly repressed by RsmA. This adds to thegrowing complexity of the signaling network associated with c-di-GMP in P. aeruginosa. While this organism possesses morethan 40 c-di-GMP-related enzymes, it remains unclear how signaling specificity is maintained within the c-di-GMP network. Thefinding that SadC but no other diguanylate cyclase is related to the formation of biofilm governed by the Gac/Rsm pathway furthercontributes to understanding of this insulation mechanism.
  • Journal article
    Matsuo E, Leon E, Matthews SJ, Roy Pet al., 2014,

    Structure based modification of Bluetongue virus helicase protein VP6 to produce a viable VP6-truncated BTV

    , BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 451, Pages: 603-608, ISSN: 0006-291X
  • Conference paper
    Mota J, Holden DW, Domingues L, 2014,

    The Salmonella effector SteA contributes to the control of membrane dynamics of Salmonella-containing vacuoles

    , FEBS EMBO 2014 Conference, Publisher: WILEY-BLACKWELL, Pages: 766-767, ISSN: 1742-464X
  • Journal article
    Collins JW, Keeney KM, Crepin VE, Rathinam VAK, Fitzgerald KA, Finlay BB, Frankel Get al., 2014,

    Citrobacter rodentium: infection, inflammation and the microbiota

    , NATURE REVIEWS MICROBIOLOGY, Vol: 12, Pages: 612-623, ISSN: 1740-1526

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