Haemophilus parasuis is the causative agent of Glässer's disease, a systemic disease of pigs, and is also associated with pneumonia. H. parasuis can be classified into 15 different serovars. Here we ...report, from the 15 serotyping reference strains, the DNA sequences of the loci containing genes for the biosynthesis of the group 1 capsular polysaccharides, which are potential virulence factors of this bacterium. We contend that these loci contain genes for polysaccharide capsule structures, and not a lipopolysaccharide O antigen, supported by the fact that they contain genes such as wza, wzb, and wzc, which are associated with the export of polysaccharide capsules in the current capsule classification system. A conserved region at the 3′ end of the locus, containing the wza, ptp, wzs, and iscR genes, is consistent with the characteristic export region 1 of the model group 1 capsule locus. A potential serovar-specific region (region 2) has been found by comparing the predicted coding sequences (CDSs) in all 15 loci for synteny and homology. The region is unique to each reference strain with the exception of those in serovars 5 and 12, which are identical in terms of gene content. The identification and characterization of this locus among the 15 serovars is the first step in understanding the genetic, molecular, and structural bases of serovar specificity in this poorly studied but important pathogen and opens up the possibility of developing an improved molecular serotyping system, which would greatly assist diagnosis and control of Glässer's disease.
Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK
Correspondence G. K. Paterson gkp27{at}cam.ac.uk
The Gram-negative Tol-Pal system of envelope ...proteins plays a key role in maintaining outer membrane integrity and contributes to the virulence of several pathogens. We have investigated the role of one of these proteins, TolA, in the biology of Salmonella enterica serovar Typhimurium. Deletion of tolA rendered strain SL1344 more susceptible to killing by bile and human serum. In addition the mutant had impaired membrane integrity and displayed alterations in LPS production. The tolA mutant was highly attenuated in mouse infections via the oral and intravenous routes. Importantly, each phenotype displayed by the mutant was complemented by provision of tolA in trans . The tolA gene therefore contributes to virulence, membrane integrity, LPS production and bile and serum resistance in S. enterica serovar Typhimurium SL1344. Finally, immunization with the tolA mutant provided significant protection against subsequent challenge with wild-type SL1344. The Tol-Pal system is therefore a potential target in the development of novel attenuated live vaccines against Salmonella and other Gram-negative pathogens.
The primary site of infection for Bordetella bronchiseptica, Bordetella pertussis and Bordetella parapertussis is the ciliated respiratory epithelium. Previous studies have implicated adherence of ...bacteria to cilia, induction of mucus production, induction of ciliostasis and damage to the ciliated epithelium in Bordetella pathogenesis. This paper describes the use of an air-interface organ culture system using canine tracheal tissue infected with B. bronchiseptica to assess the temporal relationship between these pathologies. Ciliostasis occurs very early during the host tissue-pathogen interaction, before mucus production and obvious signs of epithelial damage occur. A B. bronchiseptica bvg mutant does not colonize the organ culture model, induce ciliostasis or cause damage to the epithelial cell layer, but it does induce similar amounts of mucus release as does infection by wild-type bacteria. The authors propose that ciliostasis is a key early event during the B. bronchiseptica-host tissue interaction that abrogates the muco-ciliary defences of the host tissue, renders it susceptible to colonization by the bacteria and allows subsequent damage to the epithelium. The organ culture model described offers a physiologically relevant tool with which to characterize the molecular basis for interactions between Bordetella and its primary site of infection, the ciliated respiratory epithelium.
In Secularism In Antebellum America, John Modern extensively and directly engages with what he calls Mark Noll's “magisterial treatment of evangelicalism” in America's God. In light of this, I have ...been surprised at what a challenge it has been to bring these books into conversation with one another on the subject of evangelicals and evangelicalism. The central reason for the difficulty, I think, is that Modern's treatment of antebellum evangelical print culture—his chapter entitled “Evangelical Secularism and the Measure of Leviathan”—is not actually about evangelicals. It is about secularism. And that, in a nutshell, is Modern's point. Throughout his book, he works hard to bring what he sees as the background into the foreground, rendering the emergent atmosphere of secularism as the protagonist in his story of evangelical media practices.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK, ZRSKP
Toll-like receptors (TLRs) are a major component of the pattern recognition receptor repertoire that detect invading microorganisms and direct the vertebrate immune system to eliminate infection. In ...chickens, the differential biology of Salmonella serovars (systemic versus gut-restricted localization) correlates with the presence or absence of flagella, a known TLR5 agonist. Chicken TLR5 (chTLR5) exhibits conserved sequence and structural similarity with mammalian TLR5 and is expressed in tissues and cell populations of immunological and stromal origin. Exposure of chTLR5⁺ cells to flagellin induced elevated levels of chicken interleukin-1{szligbeta} (chIL-1{szligbeta}) but little upregulation of chIL-6 mRNA. Consistent with the flagellin-TLR5 hypothesis, an aflagellar Salmonella enterica serovar Typhimurium fliM mutant exhibited an enhanced ability to establish systemic infection. During the early stages of infection, the fliM mutant induced less IL-1{szligbeta} mRNA and polymorphonuclear cell infiltration of the gut. Collectively, the data represent the identification and functional characterization of a nonmammalian TLR5 and indicate a role in restricting the entry of flagellated Salmonella into systemic sites of the chicken.
Summary
Bordetella bronchiseptica lipopolysaccharide (LPS) expression varies depending on growth conditions, regulated by the Bvg system. A B. bronchiseptica pagP homologue was identified that is ...required for Bvg‐mediated modification of the lipid A core region of LPS that occurs on switching from the Bvg– to the Bvg+ phase. Structural analysis demonstrated that the lipid A of a B. bronchiseptica pagP mutant differed from wild‐type lipid A by the absence of a palmitate group in secondary acylation at the C3′ position. The putative pagP promoter drove the expression of a green fluorescent protein (GFP) reporter gene in a Bvg‐regulated fashion. These data suggest that B. bronchiseptica pagP encodes a Bvg‐regulated lipid A palmitoyl transferase that mediates modification of the lipid A as part of the overall Bvg‐mediated adaptation of this organism to changing environmental conditions. We also show that pagP is not required for the initial colonization of the mouse respiratory tract by B. bronchiseptica, but is required for persistence of the organism within this organ.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Invasion of macrophages by salmonellae induces cellular responses, with the bacterial inducers likely to include a number of pathogen-associated molecular patterns. LPS is one of the prime ...candidates, but its precise role in the process, especially when presented as a component of live infecting bacteria, is unclear. We thus investigated this question using the lipid A antagonist E5531, the macrophage-like cell line RAW 264.7, and primary macrophage cultures from C3H/HeJ and Toll-like receptor 4(-/-) (TLR-4(-/-)) mice. We show that LPS presented on live salmonellae provides an essential signal, via functional TLR-4, for macrophages to produce NO and TNF-alpha. Furthermore, the mitogen-activated protein kinase c-Jun N-terminal kinase and p38 are activated, and the transcription factor NF-kappa B is translocated to the nucleus when RAW 264.7 cells are presented with purified LPS or live salmonellae. Purified LPS stimulates rapid, transitory mitogen-activated protein kinase activation that is inhibited by E5531, whereas bacterial invasion stimulates delayed, prolonged activation, unaffected by E5531. Both purified LPS and bacterial invasion caused translocation of NF-kappa B, but whereas E5531 always inhibited activation by purified LPS, activation by bacterial invasion was only inhibited at later time points. In conclusion, we show for the first time that production of NO and TNF-alpha is critically dependent on activation of TLR-4 by LPS during invasion of macrophages by salmonellae, but that different patterns of activation of intracellular signaling pathways are induced by purified LPS vs live salmonellae.
PDF
