Pathogenic mycobacteria are important agents causing human disease. Mycobacterium avium subsp. hominissuis (M. avium) is a species of recalcitrant environmental pathogen. The bacterium forms robust ...biofilms that allow it to colonize and persist in austere environments, such as residential and commercial water systems. M. avium is also an opportunistic pathogen that is a significant source of mortality for immune-compromised individuals. Proteins exposed at the bacterial surface play a central role in mediating the relationship between the bacterium and its environment. The processes underlying both biofilm formation and pathogenesis are directly dependent on this essential subset of the bacterial proteome. Therefore, the characterization of the surface-exposed proteome is an important step towards an improved understanding of the mycobacterial biology and pathogenesis. Here we examined the complement of surface exposed proteins from Mycobacterium avium 104, a clinical isolate and reference strain of Mycobacterium avium subsp. hominissuis. To profile the surface-exposed proteins of viable M. avium 104, bacteria were covalently labeled with a membrane impermeable biotinylation reagent and labeled proteins were affinity purified via the biotin-streptavidin interaction. The results provide a helpful snapshot of the surface-exposed proteome of this frequently utilized reference strain of M. avium. A Cu-Zn SOD knockout mutant, MAV_2043, a surface identified protein, was evaluated regarding its role in the survival in both macrophages and neutrophils.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We consider a setting in which a firm uses residual income to motivate a manager's investment decision. Textbooks often recommend adjusting the residual income capital charge for market risk, but not ...for firm-specific risk. We demonstrate two basic flaws in this recommendation. First, the capital charge should not be adjusted for market risk. Charging a market risk premium results in "double" counting because a risk-averse manager will personally consider this risk. Second, while investors can avoid firm-specific risk through diversification, a manager cannot. If the manager faces significant firm-specific risk at the time he makes his investment decision, then it is optimal to charge him less than the riskless return so as to partially offset his reluctance to undertake risky investments. On the other hand, the manager will vary his investment decisions with the pre-decision information he receives, which accentuates his compensation risk, and the firm must compensate him for bearing this additional risk. Hence, if the manager will receive relatively precise pre-decision information, then it is optimal to charge him more than the riskless return to reduce the variability of his investment decisions.
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BFBNIB, CEKLJ, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Magnetotactic bacteria (MTB) of the genus 'Candidatus Magnetobacterium' in phylum Nitrospirae are of great interest because of the formation of hundreds of bullet-shaped magnetite magnetosomes in ...multiple bundles of chains per cell. These bacteria are worldwide distributed in aquatic environments and have important roles in the biogeochemical cycles of iron and sulfur. However, except for a few short genomic fragments, no genome data are available for this ecologically important genus, and little is known about their metabolic capacity owing to the lack of pure cultures. Here we report the first draft genome sequence of 3.42 Mb from an uncultivated strain tentatively named 'Ca. Magnetobacterium casensis' isolated from Lake Miyun, China. The genome sequence indicates an autotrophic lifestyle using the Wood-Ljungdahl pathway for CO2 fixation, which has not been described in any previously known MTB or Nitrospirae organisms. Pathways involved in the denitrification, sulfur oxidation and sulfate reduction have been predicted, indicating its considerable capacity for adaptation to variable geochemical conditions and roles in local biogeochemical cycles. Moreover, we have identified a complete magnetosome gene island containing mam, mad and a set of novel genes (named as man genes) putatively responsible for the formation of bullet-shaped magnetite magnetosomes and the arrangement of multiple magnetosome chains. This first comprehensive genomic analysis sheds light on the physiology, ecology and biomineralization of the poorly understood 'Ca. Magnetobacterium' genus.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SBNM, UL, UM, UPUK
Making accurate functional predictions for genes is a key step in this era of high throughput gene and genome sequencing. While most functional prediction methods are comparative in nature, many do ...not take advantage of the power that an evolutionary perspective provides to any comparative biology analysis. Here we review how evolutionary analysis can greatly benefit both homology-based and non-homology-based functional prediction methods. Examples that are discussed include phylogenetic determination of orthology, the use of character state reconstruction analysis of gene function, and evolutionary analysis of rates and patterns of gene evolution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and ...computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
There are many species of environmental mycobacteria (EM) that infect animals that are important to the economy and research and that also have zoonotic potential. The genomes of very few of these ...bacterial species have been sequenced, and little is known about the molecular mechanisms by which most of these opportunistic pathogens cause disease. In this study, 18 isolates of EM isolated from fish and humans (including strains of Mycobacterium avium, Mycobacterium peregrinum, Mycobacterium chelonae, and Mycobacterium salmoniphilum) were examined for their abilities to grow in macrophage lines from humans, mice, and carp. Genomic DNA from 14 of these isolates was then hybridized against DNA from an M. avium reference strain, with a custom microarray containing virulence genes of mycobacteria and a selection of representative genes from metabolic pathways. The strains of EM had different abilities to grow within the three types of cell lines, which grouped largely according to the host from which they were isolated. Genes identified as being putatively absent in some of the strains included those with response regulatory functions, cell wall compositions, and fatty acid metabolisms as well as a recently identified pathogenicity island important to macrophage uptake. Further understanding of the role these genes play in host specificity and pathogenicity will be important to gain insight into the zoonotic potential of certain EM as well as their mechanisms of virulence.
Sequencing of bacterial and archaeal genomes has revolutionized our understanding of the many roles played by microorganisms. There are now nearly 1,000 completed bacterial and archaeal genomes ...available, most of which were chosen for sequencing on the basis of their physiology. As a result, the perspective provided by the currently available genomes is limited by a highly biased phylogenetic distribution. To explore the value added by choosing microbial genomes for sequencing on the basis of their evolutionary relationships, we have sequenced and analysed the genomes of 56 culturable species of Bacteria and Archaea selected to maximize phylogenetic coverage. Analysis of these genomes demonstrated pronounced benefits (compared to an equivalent set of genomes randomly selected from the existing database) in diverse areas including the reconstruction of phylogenetic history, the discovery of new protein families and biological properties, and the prediction of functions for known genes from other organisms. Our results strongly support the need for systematic 'phylogenomic' efforts to compile a phylogeny-driven 'Genomic Encyclopedia of Bacteria and Archaea' in order to derive maximum knowledge from existing microbial genome data as well as from genome sequences to come.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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