T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.

Chronic infections promote the terminal differentiation (or "exhaustion") of T cells and are thought to preclude the formation of memory T cells. In contrast, we discovered a small subpopulation of virus-specific CD8(+) T cells that sustained the T cell response during chronic infections. These cells were defined by, and depended on, the expression of the transcription factor Tcf1. Transcriptome analysis revealed that this population shared key characteristics of central memory cells but lacked an effector signature. Unlike conventional memory cells, Tcf1-expressing T cells displayed hallmarks of an "exhausted" phenotype, including the expression of inhibitory receptors such as PD-1 and Lag-3. This population was crucial for the T cell expansion that occurred in response to inhibitory receptor blockade during chronic infection. These findings identify a memory-like T cell population that sustains T cell responses and is a prime target for therapeutic interventions to improve the immune response in chronic infections

Short Term Evolution of a Highly Transmissible Methicillin-Resistant Staphylococcus aureus Clone (ST228) in a Tertiary Care Hospital

Staphylococcus aureus is recognized as one of the major human pathogens and is by far one of the most common nosocomial organisms. The genetic basis for the emergence of highly epidemic strains remains mysterious. Studying the microevolution of the different clones of S. aureus is essential for identifying the forces driving pathogen emergence and spread. The aim of the present study was to determine the genetic changes characterizing a lineage belonging to the South German clone (ST228) that spread over ten years in a tertiary care hospital in Switzerland. For this reason, we compared the whole genome of eight isolates recovered between 2001 and 2008 at the Lausanne hospital. The genetic comparison of these isolates revealed that their genomes are extremely closely related. Yet, a few more important genetic changes, such as the replacement of a plasmid, the loss of large fragments of DNA, or the insertion of transposases, were observed. These transfers of mobile genetic elements shaped the evolution of the ST228 lineage that spread within the Lausanne hospital. Nevertheless, although the strains analyzed differed in their dynamics, we have not been able to link a particular genetic element with spreading success. Finally, the present study showed that new sequencing technologies improve considerably the quality and quantity of information obtained for a single strain; but this information is still difficult to interpret and important investments are required for the technology to become accessible for routine investigations

Comparative Genomics of Mycoplasma: Analysis of Conserved Essential Genes and Diversity of the Pan-Genome

Mycoplasma, the smallest self-replicating organism with a minimal metabolism and little genomic redundancy, is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life. This study employs comparative evolutionary analysis of twenty Mycoplasma genomes to gain an improved understanding of essential genes. By analyzing the core genome of mycoplasmas, we finally revealed the conserved essential genes set for mycoplasma survival. Further analysis showed that the core genome set has many characteristics in common with experimentally identified essential genes. Several key genes, which are related to DNA replication and repair and can be disrupted in transposon mutagenesis studies, may be critical for bacteria survival especially over long period natural selection. Phylogenomic reconstructions based on 3,355 homologous groups allowed robust estimation of phylogenetic relatedness among mycoplasma strains. To obtain deeper insight into the relative roles of molecular evolution in pathogen adaptation to their hosts, we also analyzed the positive selection pressures on particular sites and lineages. There appears to be an approximate correlation between the divergence of species and the level of positive selection detected in corresponding lineages

Complexity of the Mycoplasma fermentans M64 Genome and Metabolic Essentiality and Diversity among Mycoplasmas

Recently, the genomes of two Mycoplasma fermentans strains, namely M64 and JER, have been completely sequenced. Gross comparison indicated that the genome of M64 is significantly bigger than the other strain and the difference is mainly contributed by the repetitive sequences including seven families of simple and complex transposable elements ranging from 973 to 23,778 bps. Analysis of these repeats resulted in the identification of a new distinct family of Integrative Conjugal Elements of M. fermentans, designated as ICEF-III. Using the concept of “reaction connectivity”, the metabolic capabilities in M. fermentans manifested by the complete and partial connected biomodules were revealed. A comparison of the reported M. pulmonis, M. arthritidis, M. genitalium, B. subtilis, and E. coli essential genes and the genes predicted from the M64 genome indicated that more than 73% of the Mycoplasmas essential genes are preserved in M. fermentans. Further examination of the highly and partly connected reactions by a novel combinatorial phylogenetic tree, metabolic network, and essential gene analysis indicated that some of the pathways (e.g. purine and pyrimidine metabolisms) with partial connected reactions may be important for the conversions of intermediate metabolites. Taken together, in light of systems and network analyses, the diversity among the Mycoplasma species was manifested on the variations of their limited metabolic abilities during evolution

Genome Sequences of the High-Acetic Acid-Resistant Bacteria Gluconacetobacter europaeus LMG 18890T and G. europaeus LMG 18494 (Reference Strains), G. europaeus 5P3, and Gluconacetobacter oboediens 174Bp2 (Isolated from Vinegar) ▿

Bacteria of the genus Gluconacetobacter are usually involved in the industrial production of vinegars with high acetic acid concentrations. We describe here the genome sequence of three Gluconacetobacter europaeus strains, a very common bacterial species from industrial fermentors, as well as of a Gluconacetobacter oboediens strain

Major differences observed between the eight isolates.

<p>A difference is considered as major when it affected more than three base pairs. The position of the differences is given relative to the alignment of the eight isolates. The presence of the difference is indicated for each isolate by a cross. The type of difference (deletions, insertions or other) is described. If the difference occurred in a non-coding region it was labeled by a NC and by C when it occurred in a coding region. Finally the region or gene affected by the variation is given.</p

MRSA survey at the tertiary care hospital of Lausanne.

<p>Molecular typing was performed by Pulsed Field Gel Electrophoresis (PFGE) until 2005 and then by Double Locus Sequence Typing (DLST; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038969#pone.0038969-Kuhn1" target="_blank">[51]</a>). A. Trimestral incidence of patients with MRSA between 1999 and 2009. The four main lineages of MRSA encountered at the hospital are labeled by colors; the ST228 in red, the ST105 in violet, the ST45 in green and the ST8 in yellow. The other lineages, less common at the hospital, are in black. B. Trimestral incidence of patients with MRSA of clone ST228 at the University hospital of Lausanne between 1999 and 2009. A subset of MRSA detected between 2008 and 2009 were randomly selected for PFGE typing. The four most common pulsotypes (Da, Db,Dc and Dd) were labeled in red-like colors. C. PFGE profile of the eight isolates selected for the genome comparison. Among these eight isolates, we selected the four most common pulsotypes described in B. The eight pulsotypes were bordered by a marker (M) corresponding to the restriction of the reference strain NCTC 8325.</p

RaxML phylogeny based on the SNPs obtained after the alignment of the core genome.

<p>A. In this analysis, the strain N315 was included and used as outgroup. B. Same analysis as in A with bootstrap values given for each node. Nodes that were under the 50% majority rule were collapsed. The tree was rooted with N315 but the distance between this strain and the other was shortened to focus on the relationships between the eight isolates. C. Phylogeny based on the SNPs of the core genome based on the comparison of the eight isolates. D. Mapping of the MGEs and major differences observed between the different isolates onto the phylogenetic tree. Plasmids are represented by circle. The light blue and green circles represent the plasmids that are closely related to the published plasmid SAP064A and pUSA03, respectively. The black trait at the left side of the plasmids represents the presence of the mercuric operon whereas those on the right represent insertions of IS elements. The purple square illustrates the presence of an element of phage of about 18’500 bp. The smaller symbols describe the genetic variations described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038969#pone-0038969-t002" target="_blank">Table 2</a>. Circles were used for deletions, triangles for insertions and squares for other types of modifications. The numbers within each symbol correspond to the genetic variation described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038969#pone-0038969-t002" target="_blank">Table 2</a>. The symbols are white when the difference is unique to one isolate and colored when it is shared between different isolates.</p

Genome Sequence of Mycoplasma ovipneumoniae Strain SC01 ▿

Mycoplasma ovipneumoniae is associated with chronic nonprogressive pneumonia in both sheep and goats. Studies concerning its molecular pathogenesis, genetic analysis, and vaccine development have been hindered due to limited genomic information. Here, we announce the first complete genome sequence of this organism