Evidence for reductive genome evolution and lateral acquisition of virulence functions in two Corynebacterium pseudotuberculosis strains

Background

Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity.

Methodology and Findings

We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer.

Conclusions

These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers {"type":"entrez-nucleotide","attrs":{"text":"CP001809","term_id":"340539261","term_text":"CP001809"}}CP001809 and {"type":"entrez-nucleotide","attrs":{"text":"CP001829","term_id":"302205157","term_text":"CP001829"}}CP001829.     

Primed for pluripotency

To date, pluripotent epiblast stem cells (EpiSCs) had only been derived from postimplantation mouse embryos. In this issue of Cell Stem Cell, Najm et al. (2011) demonstrate that EpiSCs can be routinely derived from preimplantation embryos, showing that both human and mouse blastocysts can produce the same class of primed pluripotent cells.     

Disorders of agency in schizophrenia correlate with an inability to compensate for the sensory consequences of actions

Psychopathological symptoms in schizophrenia patients suggest that the concept of self might be disturbed in these individuals [1]. Delusions of influence make them feel that someone else is guiding their actions, and certain kinds of their hallucinations seem to be misinterpretations of their own inner voice as an external voice, the common denominator being that self-produced information is perceived as if coming from outside. If this interpretation were correct, we might expect that schizophrenia patients might also attribute the sensory consequences of their own eye movements to the environment rather than to themselves, challenging the percept of a stable world. Indeed, this seems to be the case because we found a clear correlation between the strength of delusions of influence and the ability of schizophrenia patients to cancel out such self-induced retinal information in motion perception. This correlation reflects direct experimental evidence supporting the view that delusions of influence in schizophrenia might be due to a specific deficit in the perceptual compensation of the sensory consequences of one's own actions [1, 2, 3, 4, 5 and 6].     

Heavy metals and thiol pool in three strains of <Emphasis Type="Italic">Tetracladium marchalianum</Emphasis>

Growth of three strains of Tetracladium marchalianum was inhibited by Cd-, and, to a lesser extent, by Cu-and Zn-chloride. In the presence of 50 μM Cd(II), all strains increased total thiol and glutathione production to 6, 11, and 21 μmoles · mg⁻¹ dry mass, respectively. Cd(II) also induced the synthesis of one to several compounds reacting with 5,5′-dithio-bis-(2-nitrobenzoic acid). In order to identify buffer-soluble thiolic compounds other than cysteine, γ-EC and γ-ECG (glutathione) were analyzed and confirmed by mass spectrometry. No water soluble sulfides were detectable in any of the culture filtrates, but Cd(II) exposure at a concentration of 50 μM raised sulfide levels in the mycelia of two of the strains between 3 and 7-fold, Cu(II) and Zn(II) had no effect. Energy Dispersive X-ray-analysis (EDX) and Electron Spectrometry-Images (ES-I) of one strain revealed increased levels of Cu and Zn in the cytoplasm and even higher levels in vacuolar precipitates. Zn and Cu are accumulated in the vacuoles as polyphosphates, identified by Electron Energy Loss-Spectrometry (EELS). Cd was found only in the vacuoles.     

Ion mobility spectrometry for microbial volatile organic compounds: a new identification tool for human pathogenic bacteria

Presently, 2 to 4 days elapse between sampling at infection suspicion and result of microbial diagnostics. This delay for the identification of pathogens causes quite often a late and/or inappropriate initiation of therapy for patients suffering from infections. Bad outcome and high hospitalization costs are the consequences of these currently existing limited pathogen identification possibilities. For this reason, we aimed to apply the innovative method multi-capillary column–ion mobility spectrometry (MCC-IMS) for a fast identification of human pathogenic bacteria by determination of their characteristic volatile metabolomes. We determined volatile organic compound (VOC) patterns in headspace of 15 human pathogenic bacteria, which were grown for 24 h on Columbia blood agar plates. Besides MCC-IMS determination, we also used thermal desorption–gas chromatography–mass spectrometry measurements to confirm and evaluate obtained MCC-IMS data and if possible to assign volatile compounds to unknown MCC-IMS signals. Up to 21 specific signals have been determined by MCC-IMS for Proteus mirabilis possessing the most VOCs of all investigated strains. Of particular importance is the result that all investigated strains showed different VOC patterns by MCC-IMS using positive and negative ion mode for every single strain. Thus, the discrimination of investigated bacteria is possible by detection of their volatile organic compounds in the chosen experimental setup with the fast and cost-effective method MCC-IMS. In a hospital routine, this method could enable the identification of pathogens already after 24 h with the consequence that a specific therapy could be initiated significantly earlier.     

Evolutionary history of the odd-nosed monkeys and the phylogenetic position of the newly described Myanmar snub-nosed monkey Rhinopithecus strykeri

Odd-nosed monkeys represent one of the two major groups of Asian colobines. Our knowledge about this primate group is still limited as it is highlighted by the recent discovery of a new species in Northern Myanmar. Although a common origin of the group is now widely accepted, the phylogenetic relationships among its genera and species, and the biogeographic processes leading to their current distribution are largely unknown. To address these issues, we have analyzed complete mitochondrial genomes and 12 nuclear loci, including one X chromosomal, six Y chromosomal and five autosomal loci, from all ten odd-nosed monkey species. The gene tree topologies and divergence age estimates derived from different markers were highly similar, but differed in placing various species or haplogroups within the genera Rhinopithecus and Pygathrix. Based on our data, Rhinopithecus represent the most basal lineage, and Nasalis and Simias form closely related sister taxa, suggesting a Northern origin of odd-nosed monkeys and a later invasion into Indochina and Sundaland. According to our divergence age estimates, the lineages leading to the genera Rhinopithecus, Pygathrix and Nasalis+Simias originated in the late Miocene, while differentiation events within these genera and also the split between Nasalis and Simias occurred in the Pleistocene. Observed gene tree discordances between mitochondrial and nuclear datasets, and paraphylies in the mitochondrial dataset for some species of the genera Rhinopithecus and Pygathrix suggest secondary gene flow after the taxa initially diverged. Most likely such events were triggered by dramatic changes in geology and climate within the region. Overall, our study provides the most comprehensive view on odd-nosed monkey evolution and emphasizes that data from differentially inherited markers are crucial to better understand evolutionary relationships and to trace secondary gene flow.