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  • Journal article
    Couchman EC, Browne HP, Dunn M, Lawley TD, Songer JG, Hall V, Petrovska L, Vidor C, Awad M, Lyras D, Fairweather NFet al., 2015,

    Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci

    , BMC Genomics, Vol: 16, ISSN: 1471-2164

    BackgroundClostridium sordellii can cause severe infections in animals and humans, the latter associated with trauma, toxic shock and often-fatal gynaecological infections. Strains can produce two large clostridial cytotoxins (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile, Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin production remains uncharacterised.ResultsPhylogenetic analysis of the genome sequences of 44 strains isolated from human and animal infections in the UK, US and Australia placed the species into four clades. Although all strains originated from animal or clinical disease, only 5 strains contained LCC genes: 4 strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin-positive strains were found within one clade. Where present, tcsL and tcsH were localised in a pathogenicity locus, similar to but distinct from that present in C. difficile. In contrast to C. difficile, where the LCCs are chromosomally localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our data suggest gain and loss of entire toxigenic plasmids in addition to horizontal transfer of the pathogenicity locus. A high quality, annotated sequence of ATCC9714 reveals many putative virulence factors including neuraminidase, phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are highly conserved between all strains studied.ConclusionsGenome analysis of C. sordellii reveals that the LCCs, the major virulence factors, are localised on plasmids. Many strains do not contain the LCC genes; it is probable that in several of these cases the plasmid has been lost upon laboratory subculture. Our data are consistent with LCCs being the primary virulence factors in the majority of infections, but LCC-negative strains may precipitate certain categories of infection. A high quality genome sequence reveals putative virulence factors whose role in virulence can be investigated.Keywords: C

  • Journal article
    Uhia I, Williams KJ, Shahrezaei V, Robertson BDet al., 2015,

    Mycobacterial growth

    , Cold Spring Harbor Perspectives in Medicine, Vol: 5, ISSN: 2157-1422

    In this work, we review progress made in understanding the molecular underpinnings of growth and division in mycobacteria, concentrating on work published since the last comprehensive review ( Hett and Rubin 2008). We have focused on exciting work making use of new time-lapse imaging technologies coupled with reporter-gene fusions and antimicrobial treatment to generate insights into how mycobacteria grow and divide in a heterogeneous manner. We try to reconcile the different observations reported, providing a model of how they might fit together. We also review the topic of mycobacterial spores, which has generated considerable discussion during the last few years. Resuscitation promoting factors, and regulation of growth and division, have also been actively researched, and we summarize progress in these areas.

  • Journal article
    Benjamin S, Williams F, Kerry L, Matthews Set al., 2015,

    NMR assignment of the immune mapped protein 1 (IMP1) homologue from Plasmodium falciparum

    , Biomolecular NMR Assignments, Vol: 9, Pages: 393-395, ISSN: 1874-2718
  • Journal article
    Hunter PJ, Shaw RK, Berger CN, Frankel G, Pink D, Hand Pet al., 2015,

    Older leaves of lettuce (Lactuca spp.) support higher levels of Salmonella enterica ser. Senftenberg attachment and show greater variation between plant accessions than do younger leaves

    , FEMS Microbiology Letters, Vol: 362, ISSN: 0378-1097

    Salmonella can bind to the leaves of salad crops including lettuce and survive for commercially relevant periods. Previous studies have shown that younger leaves are more susceptible to colonization than older leaves and that colonization levels are dependent on both the bacterial serovar and the lettuce cultivar. In this study, we investigated the ability of two Lactuca sativa cultivars (Saladin and Iceberg) and an accession of wild lettuce (L. serriola) to support attachment of Salmonella enterica serovar Senftenberg, to the first and fifth to sixth true leaves and the associations between cultivar-dependent variation in plant leaf surface characteristics and bacterial attachment. Attachment levels were higher on older leaves than on the younger ones and these differences were associated with leaf vein and stomatal densities, leaf surface hydrophobicity and leaf surface soluble protein concentrations. Vein density and leaf surface hydrophobicity were also associated with cultivar-specific differences in Salmonella attachment, although the latter was only observed in the older leaves and was also associated with level of epicuticular wax.

  • Journal article
    Willing SE, Candela T, Shaw HA, Seager Z, Mesnage S, Fagan RP, Fairweather NFet al., 2015,

    Clostridium difficile surface proteins are anchored to the cell wall using CWB2 motifs that recognise the anionic polymer PSII

    , MOLECULAR MICROBIOLOGY, Vol: 96, Pages: 596-608, ISSN: 0950-382X
  • Journal article
    Aragon IM, Pérez-Mendoza D, Moscoso JA, Faure E, Guery B, Gallegos M-T, Filloux A, Ramos Cet al., 2015,

    Diguanylate cyclase DgcP is involved in plant and human Pseudomonas spp. infections

    , Environmental Microbiology, Vol: 17, Pages: 4332-4351, ISSN: 1462-2920

    The second messenger cyclic di-GMP (c-di-GMP) controls the transition between different lifestyles in bacterial pathogens. Here, we report the identification of DgcP (diguanylate cyclase conserved in Pseudomonads), whose activity in the olive tree pathogen Pseudomonas savastanoi pv. savastanoi is dependent on the integrity of its GGDEF domain. Furthermore, deletion of the dgcP gene revealed that DgcP negatively regulates motility and positively controls biofilm formation in both the olive tree pathogen P. savastanoi pv. savastanoi and the human opportunistic pathogen Pseudomonas aeruginosa. Overexpression of the dgcP gene in P. aeruginosa PAK led to increased exopolysaccharide production and upregulation of the type VI secretion system; in turn, it repressed the type III secretion system, which is a hallmark of chronic infections and persistence for P. aeruginosa. Deletion of the dgcP gene in P. savastanoi pv. savastanoi NCPPB 3335 and P. aeruginosa PAK reduced their virulence in olive plants and in a mouse acute lung injury model respectively. Our results show that diguanylate cyclase DgcP is a conserved Pseudomonas protein with a role in virulence, and confirm the existence of common c-di-GMP signalling pathways that are capable of regulating plant and human Pseudomonas spp. infections.

  • Journal article
    Taylor JD, Matthews SJ, 2015,

    New insight into the molecular control of bacterial functional amyloids.

    , Frontiers in Cellular and Infection Microbiology, Vol: 5, ISSN: 2235-2988

    Amyloid protein structure has been discovered in a variety of functional or pathogenic contexts. What distinguishes the former from the latter is that functional amyloid systems possess dedicated molecular control systems that determine the timing, location, and structure of the fibers. Failure to guide this process can result in cytotoxicity, as observed in several pathologies like Alzheimer's and Parkinson's Disease. Many gram-negative bacteria produce an extracellular amyloid fiber known as curli via a multi-component secretion system. During this process, aggregation-prone, semi-folded curli subunits have to cross the periplasm and outer-membrane and self-assemble into surface-attached fibers. Two recent breakthroughs have provided molecular details regarding periplasmic chaperoning and subunit secretion. This review offers a combined perspective on these first mechanistic insights into the curli system.

  • Journal article
    Gross CA, Gruendling A, 2015,

    Editorial overview: Cell regulation: When you think you know it all, there is another layer to be discovered

    , CURRENT OPINION IN MICROBIOLOGY, Vol: 24, Pages: V-VII, ISSN: 1369-5274
  • Journal article
    Liu B, Zhu F, Wu H, Matthews Set al., 2015,

    NMR assignment of the amylase-binding protein A from Streptococcus parasanguinis

    , BIOMOLECULAR NMR ASSIGNMENTS, Vol: 9, Pages: 173-175, ISSN: 1874-2718
  • Journal article
    Almeida MT, Mesquita FS, Cruz R, Osorio H, Custodio R, Brito C, Vingadassalom D, Martins M, Leong JM, Holden DW, Cabanes D, Sousa Set al., 2015,

    Src-dependent Tyrosine Phosphorylation of Non-muscle Myosin Heavy Chain-IIA Restricts Listeria monocytogenes Cellular Infection

    , JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 290, Pages: 8383-8395

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