The Csr/Rsm system of Yersinia and related pathogens: A post-transcriptional strategy for managing virulence

This review emphasizes the function and regulation of the Csr regulatory system in the human enteropathogen Yersinia pseudotuberculosis and compares its features with the homologous Csr/Rsm systems of related pathogens. The Csr/Rsm systems of eubacteria form a complex regulatory network in which redundant non-translated Csr/Rsm-RNAs bind the RNA-binding protein CsrA/RsmA, thereby preventing its interaction with mRNA targets. The Csr system is controlled by the BarA/UvrY-type of two-component sensor-regulator systems. Apart from that, common or pathogen-specific regulators control the abundance of the Csr components. The coordinate control of virulence factors and infection-linked physiological traits by the Csr/Rsm systems helps the pathogens to adapt individually to rapidly changing conditions to which they are exposed during the different stages of an infection. As Csr/Rsm function is relevant for full virulence, it represents a target suitable for antimicrobial drug development.     

Primary central nervous system angiosarcoma: two case reports

ABSTRACT: INTRODUCTION: Primary angiosarcoma of the brain is extremely rare; only 15 cases have been reported inadults over the last 25 years.Case presentationsWe describe two cases of primary angiosarcoma of the brain that are well characterized byimaging, histopathology, and immunohistochemistry. Case 1: our first patient was a 35-yearoldwoman who developed exophthalmos. Subtotal resection of a left extra-axial retro-orbitalmass was performed. Case 2: our second patient was a 47-year-old man who presented to ourfacility with acute visual loss, word-finding difficulty and subtle memory loss. Aheterogeneously-enhancing left sphenoid wing mass was removed. We also review theliterature aiming at developing a rational approach to diagnosis and treatment, given the rarityof this entity. CONCLUSIONS: Gross total resection is the standard of care for primary angiosarcoma of the brain. Adjuvantradiation and chemotherapy are playing increasingly recognized roles in the therapy of theserare tumors.     

Design and evaluation of novel primers for the detection of genes encoding diverse enzymes of methylotrophy and autotrophy

The phylogenetic significance of the diversity of key enzymes of methylotrophic and autotrophic metabolism is discussed. Primers for these key enzymes were designed using gene sequences encoding methanol dehydrogenase (mxaF; using subsets from database sequences for 22 Bacteria), hydroxypyruvate reductase (hpr; 36 sequences), methylamine dehydrogenase (mauA; 12 sequences), methanesulfonate monooxygenase (msmA; four sequences), and the ccbL and cbbM genes of ribulose bisphosphate carboxylase (26 and 23 sequences). These were effective in amplifying the correct gene products for the target genes in reference organisms and in test organisms not previously shown to contain the genes, as well as in some methylotrophic Proteobacteria isolated from the human mouth. The availability of the new primers increases the probability of detecting diverse examples of the genes encoding these key enzymes both in natural populations and in isolated bacterial strains.     

Host genetic and environmental effects on mouse intestinal microbiota

The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strain-specific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.     

Evaluation of Cruzia americana, Turgida turgida, and Didelphostrongylus hayesi infection in the Virginia opossum (Didelphis virginiana) and risk factors along the California coast

Three nematodes, Turgida turgida, Cruzia americana, and Didelphostrongylus hayesi, have been documented to cause morbidity and mortality in the Virginia opossum (Didelphis virginiana). The present study was designed to determine the frequency of infection of these nematodes in opossums at 2 study sites in California and to determine if there are risk factors associated with shedding of eggs or larvae in the feces. Turgida turgida and C. americana adults were found in 84.4% (stomach; n = 45) and 62.5% (intestinal wash and feces; n = 16) of sampled opossums. Eggs were present in opossum feces (n = 105) less frequently (40% T. turgida and 35.2% C. americana). Didelphostrongylus hayesi larvae were found in 79.0% of opossum feces examined (n = 105). Adult age and wet season (December through April) were significant predictive factors for the presence of T. turgida eggs, whereas the dry season (May through November) was significantly associated with the presence of C. americana eggs in feces. Adult opossums were more likely to have eggs and larvae from all 3 nematodes in the feces.     

Early resolution of acute immune activation and induction of PD-1 in SIV-infected sooty mangabeys distinguishes nonpathogenic from pathogenic infection in rhesus macaques

Primate lentiviruses are typically apathogenic in their evolutionarily coadapted host species but can be lethal when transferred to new host species. Why such infections are pathogenic in humans and rhesus macaques (RMs) but not in sooty mangabeys (SMs), a natural host, remains unclear. Studies of chronically infected animals point to the importance of diminished immune activation in response to the infection in SMs. In this study, we sought the causes and timing of the differences in immune activation in a comparative study of acute SIV infection in RMs and SMs. Surprisingly, we show that in acute infection immune activation is comparable in SMs and RMs but thereafter, SMs quickly resolve immune activation, whereas RMs did not. Early resolution of immune activation in SMs correlated with increased expression of PD-1 and with preservation of CD4(+) T cell counts and lymphatic tissue architecture. These findings point to early control of immune activation by host immunoregulatory mechanisms as a major determinant of the different disease outcomes in SIV infection of natural vs non-natural hosts.     

The mouse polyubiquitin gene Ubb is essential for meiotic progression

Ubiquitin is encoded in mice by two polyubiquitin genes, Ubb and Ubc, that are considered to be stress inducible and two constitutively expressed monoubiquitin (Uba) genes. Here we report that targeted disruption of Ubb results in male and female infertility due to failure of germ cells to progress through meiosis I and hypogonadism. In the absence of Ubb, spermatocytes and oocytes arrest during meiotic prophase, before metaphase of the first meiotic division. Although cellular ubiquitin levels are believed to be maintained by a combination of functional redundancy among the four ubiquitin genes, stress inducibility of the two polyubiquitin genes, and ubiquitin recycling by proteasome-associated isopeptidases, our results indicate that ubiquitin is required for and consumed during meiotic progression. The striking similarity of the meiotic phenotype in Ubb^−/− germ cells to the sporulation defect in fission yeast (Schizosaccharomyces pombe) lacking a polyubiquitin gene suggests that a meiotic role of the polyubiquitin gene has been conserved throughout eukaryotic evolution.