Evolution of an endofungal Lifestyle: Deductions from the Burkholderia rhizoxinica Genome

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia rhizoxinica </it>is an intracellular symbiont of the phytopathogenic zygomycete <it>Rhizopus microsporus</it>, the causative agent of rice seedling blight. The endosymbiont produces the antimitotic macrolide rhizoxin for its host. It is vertically transmitted within vegetative spores and is essential for spore formation of the fungus. To shed light on the evolution and genetic potential of this model organism, we analysed the whole genome of <it>B. rhizoxinica </it>HKI 0454 - a type strain of endofungal <it>Burkholderia </it>species.</p> <p>Results</p> <p>The genome consists of a structurally conserved chromosome and two plasmids. Compared to free-living <it>Burkholderia </it>species, the genome is smaller in size and harbors less transcriptional regulator genes. Instead, we observed accumulation of transposons over the genome. Prediction of primary metabolic pathways and transporters suggests that endosymbionts consume host metabolites like citrate, but might deliver some amino acids and cofactors to the host. The rhizoxin biosynthesis gene cluster shows evolutionary traces of horizontal gene transfer. Furthermore, we analysed gene clusters coding for nonribosomal peptide synthetases (NRPS). Notably, <it>B. rhizoxinica </it>lacks common genes which are dedicated to quorum sensing systems, but is equipped with a large number of virulence-related factors and putative type III effectors.</p> <p>Conclusions</p> <p><it>B. rhizoxinica </it>is the first endofungal bacterium, whose genome has been sequenced. Here, we present models of evolution, metabolism and tools for host-symbiont interaction of the endofungal bacterium deduced from whole genome analyses. Genome size and structure suggest that <it>B. rhizoxinica </it>is in an early phase of adaptation to the intracellular lifestyle (genome in transition). By analysis of tranporters and metabolic pathways we predict how metabolites might be exchanged between the symbiont and its host. Gene clusters for biosynthesis of secondary metabolites represent novel targets for genomic mining of cryptic natural products. <it>In silico </it>analyses of virulence-associated genes, secreted proteins and effectors might inspire future studies on molecular mechanisms underlying bacterial-fungal interaction.</p

The Atypical Calpains: Evolutionary Analyses and Roles in Caenorhabditis elegans Cellular Degeneration

The calpains are physiologically important Ca2+-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca2+]i. We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca2+ dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover

Organization and function of the plant pleiotropic drug resistance ABC transporter family

Among the ABC transporters, the pleiotropic drug resistance (PDR) family is particular in that its members are found only in fungi and plants and have a reverse domain organization, i.e., the nucleotide binding domain precedes the transmembrane domain. In Arabidopsis and rice, for which the full genome has been sequenced, the family of plant ABC transporters contains 15 and 23 PDR genes, respectively, which can be tentatively organized using the sequence data into five subfamilies. Most of the plant PDR genes so far characterized belong to subfamily I and have been shown to be involved in responses to abiotic and biotic stress, in the latter case, probably by transporting antimicrobial secondary metabolites to the cell surface. Only a single subfamily II member has been characterized. Induction of its expression by iron deficiency suggests its involvement in iron deficiency stress, thus, enlightening a new physiological role for a PDR gene. (c) 2005 Federation of European Biochemical Societies. Published by Else-tier B.V. All rights reserved

The economics of cochlear implant management in France: a multicentre analysis

Cochlear implantation, Clinical management, Economic analysis,

The development of lower limb musculoskeletal models with clinical relevance is dependent upon the fidelity of the mathematical description of the lower limb. Part 1: equations of motion

Contemporary musculoskeletal modelling research is based upon the assumption that such models will evolve into clinical tools that can be used to guide therapeutic interventions. However, there are a number of questions that must be addressed before this becomes a reality. At its heart, musculoskeletal modelling is a process of formulating and then solving the equations of motion that describe the movement of body segments. Both of these steps are challenging. This article argues that traditional approaches to musculoskeletal modelling have been heavily influenced by the need to simplify this process (and in particular the solution process), and that this has to some degree resulted in approaches that are contrary to the principles of classical mechanics. It is suggested that future work is required to understand how these simplifications affect the outputs of musculoskeletal modelling studies. Equally, to increase their clinical relevance, the models of the future should adhere more closely to the classical mechanics on which they are based

Ectomycorrhizal Helper Bacteria: The Third Partner in the Symbiosis

In natural conditions, mycorrhizal fungi are surrounded by complex microbial communities, which may trigger various responses, from enhancement of the establishment of mycorrhizal symbiosis to mycelial growth inhibition or cell death. The symbiosis between mycorrhizal soil fungi and higher plants takes advantage of active collaboration with specific helper bacteria. Thus, a symbiosis so far thought of involving two components could be the result of the interaction among at least three different partners. This chapter focuses on the relationship between edible ectomycorrhizal mushrooms and soil bacteria, in particular nitrogen-fixing bacteria associated with Tuber species. The ability of these bacteria to modify nutrient availability during the fructification phase is very important to truffle development. This chapter will also discuss perspectives on the beneficial use of ectomycorrhizal symbiosis with nitrogen-fixing bacteria to develop predictive models that could be used to improve the mycorrhization processes with the further aim of obtaining plants infected with Tuber magnatum Pico, the most economically important truffle species that remains difficult to cultivat