Genomic characterization of the Yersinia genus

Comparative Yersinia genomics identifies features responsible for the colonization of specific host habitats and the horizontal transfer of virulence determinants

Widespread horizontal transfer of mitochondrial genes in flowering plants

Horizontal gene transfer - the exchange of genes across mating barriers - is recognized as a major force in bacterial evolution(1,2). However, in eukaryotes it is prevalent only in certain phagotrophic protists and limited largely to the ancient acquisition of bacterial genes(3-5). Although the human genome was initially reported(6) to contain over 100 genes acquired during vertebrate evolution from bacteria, this claim was immediately and repeatedly rebutted(7,8). Moreover, horizontal transfer is unknown within the evolution of animals, plants and fungi except in the special context of mobile genetic elements(9-12). Here we show, however, that standard mitochondrial genes, encoding ribosomal and respiratory proteins, are subject to evolutionarily frequent horizontal transfer between distantly related flowering plants. These transfers have created a variety of genomic outcomes, including gene duplication, recapture of genes lost through transfer to the nucleus, and chimaeric, half-monocot, half-dicot genes. These results imply the existence of mechanisms for the delivery of DNA between unrelated plants, indicate that horizontal transfer is also a force in plant nuclear genomes, and are discussed in the contexts of plant molecular phylogeny and genetically modified plants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62688/1/nature01743.pd

Anthrolysin O: The cholesterol -dependent cytolysin of <italic>Bacillus anthracis</italic>.

While each branch of the immune system works cooperatively to defend its host, often the effectiveness of early, innate defenses, such as phagocytes, determines the overall success of the battles against pathogens. Bacillus anthracis has evolved means by which to survive this innate defense, permitting both the escape of the bacilli from the phagosome and the release from the phagocyte. While Lethal Toxin (LeTx) is the primary agent responsible for the progression of anthrax, we have previously shown that LeTx is not required for the escape/release phenomenon. We found that B. anthracis encodes four potential membrane-active proteins (MAPs), and one such protein, subsequently named anthrolysin O (ALO), is a putative member of the family of cholesterol-dependent cytolysins (CDCs). Because ALO is more than 60% similar at the amino acid level to the Listeria monocytogenes orthologue listeriolysin O (LLO) and because of the transient intracellular lifestyle of B. anthracis, I hypothesized that ALO functions as mediator cellular escape. Through the use of erythrocyte hemolysis assays, ALO became firmly established as a member of the CDC family of cytotoxins, and gain-of-function studies illustrated that the expression of aloA by Bacillus subtilis and LLO-null L. monocytogenes was sufficient to permit phagosomal escape from these typically escape-incompetent strains. Deletion studies were utilized to investigate the essentiality of ALO for B. anthracis in both in vitro and in vivo models of anthrax. B. anthracis Delta aloA was found to be indistinguishable from wildtype Sterne in bone marrow-derived macrophages and in DBA2/J mice. Because the presence of four putative membrane-active proteins made redundancy of function a possibility, knock-out strains of each of the MAPs in all combinations were constructed. Ultimately, the quadruple mutant, a strain deleted for all four MAPs, showed neither the ability to grow within nor cytotoxicity to macrophages. Furthermore, the quadruple mutant was nearly 40-fold less virulent than the wildtype strain in the mouse model. With this body of work, I have shown that ALO is indeed a functional member of the CDC family of proteins, capable of mediating bacterial escape from host cells. And while aloA is not an essential element of anthrax pathogenesis in the models tested, it is part of a repertoire of MAPs required for full virulence.Ph.D.BiochemistryBiological SciencesMicrobiologyPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125763/2/3208558.pd

Bacillus anthracis Phospholipases C Facilitate Macrophage-Associated Growth and Contribute to Virulence in a Murine Model of Inhalation Anthrax

Several models of anthrax pathogenesis suggest that early in the infectious process Bacillus anthracis endospores germinate and outgrow into vegetative bacilli within phagocytes before being released into the blood. Here, we define the respective contributions of three phospholipases C (PLCs) to the pathogenesis of B. anthracis. Genetic deletions of the PLCs were made in the Sterne 7702 background, resulting in the respective loss of their activities. The PLCs were redundant both in tissue culture and in murine models of anthrax. Deletion of all three PLC genes was required for attenuation of virulence in mice after intratracheal inoculation. This attenuation may be attributed to the inability of the PLC-null strain to grow in association with the macrophage. Complementation of these defects in both models of anthrax was achieved by expression of the PLC genes in trans. The functional redundancy between PLCs in the virulence of B. anthracis implies that their activities are important for anthrax pathogenesis

Formation and Composition of the Bacillus anthracis Endospore

The endospores of Bacillus anthracis are the infectious particles of anthrax. Spores are dormant bacterial morphotypes able to withstand harsh environments for decades, which contributes to their ability to be formulated and dispersed as a biological weapon. We monitored gene expression in B. anthracis during growth and sporulation using full genome DNA microarrays and matched the results against a comprehensive analysis of the mature anthrax spore proteome. A large portion (∼36%) of the B. anthracis genome is regulated in a growth phase-dependent manner, and this regulation is marked by five distinct waves of gene expression as cells proceed from exponential growth through sporulation. The identities of more than 750 proteins present in the spore were determined by multidimensional chromatography and tandem mass spectrometry. Comparison of data sets revealed that while the genes responsible for assembly and maturation of the spore are tightly regulated in discrete stages, many of the components ultimately found in the spore are expressed throughout and even before sporulation, suggesting that gene expression during sporulation may be mainly related to the physical construction of the spore, rather than synthesis of eventual spore content. The spore also contains an assortment of specialized, but not obviously related, metabolic and protective proteins. These findings contribute to our understanding of spore formation and function and will be useful in the detection, prevention, and early treatment of anthrax. This study also highlights the complementary nature of genomic and proteomic analyses and the benefits of combining these approaches in a single study

Mandibular two implant-supported overdentures as the first choice standard of care for edentulous patients - The york consensus statement

The Annual Conference of the BSSPD (British Society for the Study of Prosthetic Dentistry) was held in York on 6 and 7 April 2009. At the symposium on mandibular overdentures, presenters offered a synopsis of the research available on the efficacy of implant-supported mandibular overdentures in the edentulous mandible. Emphasis was given to both qualitative and quantitative research based on patient-centred outcomes of treatment. A draft consensus was circulated to all presenters and to the Council members of the BSSPD and to BSSPD members on the Society's website. The statement was modified in the light of their comments, audience feedback following the presentations and members' feedback. We hope that this consensus statement will be a useful guide for patients and clinicians and that it will act to stimulate wider debate. We also hope that it will prove useful to other patient and professional organisations and will inform discussions with providers of national healthcare and with independent funders

Neural and behavioral responses to threatening emotion faces in children as a function of the short allele of the serotonin transporter gene

Data suggest that a genetic polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (5-HTT) gene (SLC6A4) mediates stress reactivity in adults. Little is known, however, about this gene-brain association in childhood and adolescence, generally conceptualized as a time of heightened stress reactivity. The present study examines the association between 5-HTT allelic variation and responses to emotional faces presented both sub- and supraliminally in 9- to 17-year-old participants. Behaviorally, carriers of the 5-HTTLPR short (s) allele exhibited significantly greater attentional bias to subliminally presented fear faces than did their long (l)-allele homozygous counterparts. Moreover, s-allele carriers showed greater neural activations to emotion faces than did l-allele homozygotes in various regions of association cortex previously linked to attention control in adults; no such associations were observed in the amygdala. These results indicate that child and young adolescent s-allele carriers can be distinguished from l-allele homozygotes on the basis of hypervigilant behavioral and neural processing of negative material in the environmen