90 research outputs found

    Genomic blueprint of a relapsing fever pathogen in 15th century Scandinavia

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    Louse-borne relapsing fever (LBRF) is known to have killed millions of people over the course of European history and remains a major cause of mortality in parts of the world. Its pathogen, Borrelia recurrentis, shares a common vector with global killers such as typhus and plague and is known for its involvement in devastating historical epidemics such as the Irish potato famine. Here, we de- scribe a European and historical genome of B. recurrentis, recov- ered from a 15th century skeleton from Oslo. Our distinct European lineage has a discrete genomic makeup, displaying an ancestral oppA- 1 gene and gene loss in antigenic variation sites. Our results illustrate the potential of ancient DNA research to elucidate dynamics of re- ductive evolution in a specialized human pathogen and to uncover aspects of human health usually invisible to the archaeological record

    Tuberculosis due to Resistant Haarlem Strain, Tunisia

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    Multidrug-resistant tuberculosis was diagnosed in 21 HIV-negative, nonhospitalized male patients residing in northern Tunisia. A detailed investigation showed accelerated transmission of a Mycobacterium tuberculosis clone of the Haarlem type in 90% of all patients. This finding highlights the epidemic potential of this prevalent genotype

    Phylogeny of Mycobacterium tuberculosis Beijing Strains Constructed from Polymorphisms in Genes Involved in DNA Replication, Recombination and Repair

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    The original publication is available at http:/www.plosone.orgBackground: The Beijing family is a successful group of M. tuberculosis strains, often associated with drug resistance and widely distributed throughout the world. Polymorphic genetic markers have been used to type particular M. tuberculosis strains. We recently identified a group of polymorphic DNA repair replication and recombination (3R) genes. It was shown that evolution of M. tuberculosis complex strains can be studied using 3R SNPs and a high-resolution tool for strain discrimination was developed. Here we investigated the genetic diversity and propose a phylogeny for Beijing strains by analyzing polymorphisms in 3R genes. Methodology/Principal Findings: A group of 3R genes was sequenced in a collection of Beijing strains from different geographic origins. Sequence analysis and comparison with the ones of non-Beijing strains identified several SNPs. These SNPs were used to type a larger collection of Beijing strains and allowed identification of 26 different sequence types for which a phylogeny was constructed. Phylogenetic relationships established by sequence types were in agreement with evolutionary pathways suggested by other genetic markers, such as Large Sequence Polymorphisms (LSPs). A recent Beijing genotype (Bmyc10), which included 60% of strains from distinct parts of the world, appeared to be predominant. Conclusions/Significance: We found SNPs in 3R genes associated with the Beijing family, which enabled discrimination of different groups and the proposal of a phylogeny. The Beijing family can be divided into different groups characterized by particular genetic polymorphisms that may reflect pathogenic features. These SNPs are new, potential genetic markers that may contribute to better understand the success of the Beijing family. © 2011 Mestre et al.Publishers' Versio

    Sequence alignment of IS<i>6110 orfA</i> and <i>orfB</i> haplotypes.

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    <p>Sequence alignment of IS<i>6110 orfA</i> and <i>orfB</i> haplotypes.</p

    Evolutionary Trends of the Transposase-Encoding Open Reading Frames A and B (<i>orfA</i> and <i>orfB</i>) of the Mycobacterial IS<i>6110</i> Insertion Sequence

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    <div><p>Background</p><p>The IS<i>6110</i> insertion sequence, a member of the IS3 family of insertion sequences, was found to be specific to the <i>Mycobacterium tuberculosis</i> complex (MTBC). Although IS<i>6110</i> has been extensively characterized as a transposable genetic marker, the evolutionary history of its own transposase-encoding sequence has not, to the best of our knowledge, been investigated.</p><p>Methodology/Principal Findings</p><p>Here we explored the evolution of the IS<i>6110</i> sequence by analysing the genetic variability and the selective forces acting on its transposase-encoding open reading frames (ORFs) A and B (<i>orfA</i> and <i>orfB</i>). For this purpose, we used a strain collection consisting of smooth tubercle bacilli (STB), an early branching lineage of the MTBC, and present-day <i>M</i>. <i>tuberculosis</i> strains representing the full breadth of genetic diversity in Tunisia. In each ORF, we found a major haplotype that dominated over a flat distribution of rare descendent haplotypes, consisting mainly of single- and double-nucleotide variant singletons. The predominant haplotypes consisted of both ancestral and present-day strains, suggesting that IS<i>6110</i> acquisition predated the emergence of the MTBC. There was no evidence of recombination and both ORFs were subjected to strict purifying selection, as demonstrated by their dN/dS ratios (0.29 and 0.51, respectively), as well as their significantly negative Tajima’s <i>D</i> statistics. Strikingly, the purifying selection acting on <i>orfA</i> proved much more stringent, suggesting its critical role in regulating the transpositional process. Maximum likelihood analyses further excluded any possibility of positive selection acting on single amino acid residues.</p><p>Conclusions/Significance</p><p>Taken together our data fit with an evolutionary scenario according to which the observed variability pattern of the IS<i>6110</i> transposase-encoding ORFs is generated mainly through random point mutations that accrued on a functionally optimal IS<i>6110</i> copy, whose acquisition predated the emergence of the MTBC complex. Background selection acting against deleterious mutations led to an excess of low-frequency variants.</p></div

    Patterns of molecular genetic diversity of IS<i>6110 orfA</i> and <i>orfB</i>.

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    <p>*<i>P</i>< 0.01</p><p>**<i>P</i>< 0.001</p><p>Patterns of molecular genetic diversity of IS<i>6110 orfA</i> and <i>orfB</i>.</p

    A Very Virulent Genotype of Infectious Bursal Disease Virus Predominantly Associated with Recurrent Infectious Bursal Disease Outbreaks in Tunisian Vaccinated Flocks

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    International audienceOutbreaks of infectious bursal disease (IBD) still continue to afflict the Tunisian poultry industry even in those flocks where the vaccination program is strictly applied. To characterize the viruses that circumvent protection provided by vaccination, field isolates of infectious bursal disease virus (IBDV) obtained from vaccinated flocks that have repeatedly experienced IBDV outbreak episodes were analyzed from bursal samples by reverse transcription coupled with polymerase chain reaction and dideoxynucleotide sequencing of the VP2 hypervariable region. Although sequence data were obtained from samples collected from three distinct flocks over a period of 3 years, only limited sequence variation has been observed. The few nucleotide changes were silent and the deduced amino acid sequences were identical. Thus, the virus population that predominates in the field seems to represent a homogeneous antigenic pool. Compared with the VP2 sequences of several IBDV strains, this predominant pool was found to be closely related to the very virulent (vv) IBDV viruses described in Europe and Asia. Sequence and phylogenetic analysis of the precursor polyprotein coding sequence of a representative Tunisian isolate further confirmed its assignment to the vv genotype. The deduced amino acid sequence of the whole polyprotein of the Tunisian isolate was found to be identical to a South Korean IBDV strain. Alignment of the polyprotein amino acid sequence of 35 IBDV strains identified additional mutations outside the VP2 variable domain and which occur frequently in vv strains. Based on this comparative analysis, the set of amino acid residues that should represent a typical vv profile involves Ala222, Ile242, Ile256, Ile294, Leu451, Tyr680, N685, Ser715, Asp751, Val990, and Ala1005. Such a combination of amino acid changes was observed for the majority of vvIBDV strains that define a distinct phylogroup

    Likelihood ratio test (LRT) analysis of models comparisons M1a vs M2a and M8 vs M8a.

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    <p>Likelihood ratio test (LRT) analysis of models comparisons M1a vs M2a and M8 vs M8a.</p
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