S T Cole

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..leprae genome appears to have undergone shrinkage and large-scale gene inactivation, which may account for the exceptionally slow growth of this organism...

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..These deletions affect a further seven genes, including a fourth phospholipase, plcD. In summary, the insertions and deletions described here have important implications for our understanding of the evolution of the tubercle complex...

..41 Mb genome sequence and provided fresh insight into the biochemistry, physiology. genetics and immunology of this much-feared bacterium. Genomic information is centralised in TubercuList (http://www.pasteur.fr/Bio/TubercuList/)...

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..Genomics is also furthering tuberculosis vaccine development by pinpointing potentially antigenic proteins as well as providing better diagnostic tools to detect infection...

..Evidence is presented that loss of synteny, inversion and genome downsizing may have resulted from recombination between dispersed copies of these repetitive elements...

..These do not include the oxidative stress genes ahpC and sodA, or those for siderophore production...

..Among the many other noteworthy features were ORFs encoding putative serine/threonine protein kinases and a protein phosphatase, three tRNA genes, one M. leprae-specific repetitive element and a glnQ pseudogene...

..Isoniazid is thus likely to be of no therapeutic benefit to leprosy patients...

..Repetitive sequences and insertion elements are highly abundant in M. tuberculosis, but the distribution of IS6110 is apparently nonrandom...

..microti alone or with BCG. The M. microti OV254::RD1-2F9 vaccine was less virulent and persistent in mice and than was BCG::RD1-2F9 may represent a safer alternative to BCG::RD1-2F9...

..Two other reading frames, linked to nagH, also appear to encode proteins with sugar-binding motifs...

..tuberculosis, M. smegmatis, and Escherichia coli was demonstrated by Western blotting (immunoblotting). Homologous genes were detected in other mycobacteria, even those which are naturally insensitive to isoniazid...

..The reliability of the method has been tested on a sample of known drug-resistant and susceptible isolates of M. leprae...

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..This minireview summarises the different techniques that have been employed to compare these genomes and gives an overview of the wealth of data that has already been generated by mycobacterial comparative genomics...

..This may explain the unusually long generation time and account for our inability to culture the leprosy bacillus...

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..bovis lineage separated from the M. tuberculosis lineage. This observation suggests that the common ancestor of the tubercle bacilli resembled M. tuberculosis or M. canettii and could well have been a human pathogen already...

..Comparative genomic analyses also suggest that loss of genes is part of the ongoing evolution of the slow-growing mycobacterial pathogens and might also explain how the vaccine strain BCG became attenuated...

..Knocking-in five other RD loci did not affect the virulence of BCG. This study describes a genetic lesion that contributes to safety and opens new avenues for vaccine development...

..Mutations to this domain may account for the natural lack of toxicity of the alpha-toxin homologue, phospholipase C of Clostridium bifermentans...

..The second group comprises a frequently occurring amino acid substitution and a single mutation that are both located in the C-terminal domain but do not noticeably alter either enzyme activity or heat stability...

..avium, M. gordonae, and M. szulgai, that are naturally resistant to streptomycin. This suggests that permeability barriers may be responsible for the resistance to the antibiotic...

..leprae. This is the first evidence for genomic variability in the leprosy bacillus and might ultimately be useful for developing a molecular test capable of distinguishing between strains of M. leprae...

..perfringens, Clostridium beijerinckii, and Bacillus subtilis, revealed a similar order and distribution of key sporulation and heat shock genes which might reflect an ancient evolutionary relationship...

..In these cases, the HindIII repeat was not linked to the cpe gene although this was generally preceded by ORF3...

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..In neither of these systems was any loss of fitness associated with inactivation of mntH, demonstrating that Nramp orthologues are not important determinants of mycobacterial virulence...

..microti-specific deleted regions have been identified (MiD1 to MiD3). Deletion of MiD1 has removed parts of the direct repeat region in M. microti and thus contributes to the characteristic spoligotype of M. microti strains...

..tuberculosis, showing less severe pathology and reduced dissemination of the pathogen, as compared with control animals immunized with BCG alone...

..Only one of the genes from pIP404 was expressed at a significant level in Escherichia coli, suggesting that the atypical codon usage could represent a major obstacle to heterologous gene expression...

..More than 98% of the M. leprae genome is now covered by overlapping large insert genomic clones representing a renewable source of well defined DNA segments and a powerful tool for functional genomics...

..tuberculosis. In addition, it is shown that the genes encoding aspartate semialdehyde dehydrogenase, asd, and an anonymous protein antigen recognized by sera from leprosy patients, are linked to the M. leprae att-pSAM2 locus...

..The standardized procedure could now be used in a prospective study of potential rifampicin resistance among multibacillary patients...

..ulcerans, such as TB10.4, the 19 kDa antigen, PstS3 and Hsp70, may be interesting to consider as subunit vaccines in future prospects...

..The Tat system thus contributes in multiple ways to survival of the tubercle bacillus...

..The present study has allowed us to identify new aspects of the extRD1 region of M. tuberculosis and to explore its role in the pathogenesis of tuberculosis...

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..Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection...

..This finding established a link between the PhoP regulator and ESAT-6 secretion that opens exciting new perspectives for elucidating virulence regulation in M. tuberculosis...

..Furthermore, the combined findings suggest that early BCG vaccines may even be superior to the later ones that are more widely used...

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..Analysis of the GlpC primary structure indicated that the protein lacked extended hydrophobic sequences with the potential to form alpha-helices but did contain several long segments capable of forming transmembrane amphipathic helices...

..ulcerans isolates are able to invade the salivary glands, a site where they proliferate. Later, the raptorial legs of Naucoris are covered by M. ulcerans-containing material that displays features of biofilms...

..These results question the broadly admitted correlation between the frequency of IFN-gamma-producing CD4+ T cells and the level of protection against tuberculosis...

..ulcerans into the HC, in contrast to the next step, colonization of the salivary glands; second, M. ulcerans clusters bind a member of the serpin protein family present in the salivary gland homogenate...

..Moreover, they highlight a potential interest in mycolactone as a novel immunosuppressive agent...

..These modifications can explain the previously described improved protective capacity of BCG::RD1 vaccine candidate against M. tuberculosis challenge...

..For designing subunit vaccines, attenuated or improved recombinant whole-cell live vaccines, information from the genomes of the human host and pathogenic mycobacterial species is of great help...

..ulcerans and M. marinum. This work offers significant insight into the biology and evolution of mycobacterial pathogens and is an important component of international efforts to counter Buruli ulcer...

..The results of this study support a model whereby biofilm changes confer selective advantages to M. ulcerans in colonizing various ecological niches successfully, with repercussions for Buruli ulcer pathogenesis...

..In hosts sensitized with M. avium, potent immunogenicity of ESAT-6 and increased persistence of BCG::RD1 may allow this recombinant vaccine to overcome preexisting antimycobacterial responses...

..We adapted the QuantiTect Whole Transcriptome Kit (Qiagen) to our purposes and designated the method as Whole Transcriptome Amplification (WTA)...

..Water bugs, such as Naucoris cimicoides, a potential vector of M. ulcerans, were shown to be infected specifically by this bacterium after feeding on snails experimentally exposed to M. ulcerans...

..tuberculosis, their regulation mechanisms and putative substrates, and we explore their therapeutic potential as possible targets for the development of new anti-mycobacterial compounds...

..Taken together, these results show that PPE68 is an immunogenic product of the RD1 region, which does not interfere with the secretion and immunogenicity of CFP-10 and ESAT-6...

..The implications of this finding for the transmission and reactivation of multidrug-resistant strains of M. tuberculosis are severe...

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..Here, we discuss these findings and their implications for the development of new therapeutic and prophylactic interventions against tuberculosis...

..However, the many analogues which inhibited the growth of M. tuberculosis in the 0.6-5 microg/mL range turned out to be also cytotoxic on VERO cells growth at the same concentration range...

..Presently, it is possible to assign a function to 2058 proteins (52% of the 3995 proteins predicted) and only 376 putative proteins share no homology with known proteins and thus could be unique to M. tuberculosis...

..Phylogenetic analysis of the primary structures of ten site-specific recombinases suggested a common descent and showed the RES protein to be closest to the resolvase encoded by Tn917 from Streptococcus faecalis...

..The ensuing model of PknB-GarA interactions suggests a substrate recruitment mechanism that might apply to other mycobacterial kinases bearing multiple phosphorylation sites in their activation loops...

..These findings demonstrate that the Ser/Thr protein kinase PknB is essential for sustaining mycobacterial growth and support the development of protein kinase inhibitors as new potential antituberculosis drugs...

..This study provides the immunological framework for the development of a specific, peptide-based immunodiagnostic test for leprosy...

..tuberculosis is the interaction with biomembranes that occurs after dissociation from its putative chaperone CFP-10 under acidic conditions typically encountered in the phagosome...

..Subcellular fractionation studies and immunoelectron microscopy localized many PE-PGRS proteins in the cell wall and cell membrane of M. tuberculosis. The data suggest that some PE-PGRS proteins are variable surface antigens...

..Among them, two class II proteins, ML0308 and ML2498, showed marked humoral and cellular immunogenicity, therefore providing promising candidates for the diagnosis of both tuberculoid and lepromatous forms of leprosy...

..tuberculosis complex recently presented...

..We wish to report here the preparation of some structural analogues along with their biological effect on the growth of Mycobacterium smegmatis, M. tuberculosis, as well as on VERO cells for the most active compound...

..The results presented here provide important insights into this unusual virulence plasmid from an emerging but neglected human pathogen...

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..bovis, implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence therefore offers major insight on the evolution, host preference, and pathobiology of M. bovis...

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..Studies with two mutant frd promoters from Escherichia coli, displaying altered regulation and FNR response, provided additional evidence for recognition of this sequence by FNR...

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..leprae but also between biopsy samples from the same patient, these VNTR may be too dynamic for use as epidemiological markers for leprosy...

..Such detailed knowledge of mycolactone will further the investigation of its mode of action and the development of urgently needed therapeutic strategies to combat Buruli ulcer...

..Our results suggest that pMUM is a defining characteristic of M. ulcerans but that in the absence of purifying selection, deletion of plasmid sequences and a corresponding loss of mycolactone production readily arise...

..The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years...

..The part dedicated to influenza viruses was based on consensus sequences specific for one gene generated from global alignments of a large number of influenza virus sequences available in databanks...

..Here, the ecology, microbiology, evolutionary genomics and immunopathology of Buruli ulcer are reviewed...

..The 16 SNP subtypes showed a strong geographical association that reflects the migration patterns of early humans and trade routes, with the Silk Road linking Europe to China having contributed to the spread of leprosy...

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..The ML2640c crystal structures offer the first structural glimpses at this important family of mycobacterial proteins and lend strong support to their functional assignment as AdoMet-dependent methyltransferases...

..tuberculosis. The work described herein provides a foundation for using M. marinum to better understand the determinants of pathogenesis of tuberculosis...

..The results indicate that while rifampin may be active against M. ulcerans, it should never be used as monotherapy in humans...

..Their biological evaluation on the growth of Mycobacterium smegmatis as well as Mycobacterium tuberculosis pointed out that some analogues were four times more active than the initial hit...

..bovis and M. tuberculosis, when it is important to distinguish between zoonotic sources (i.e., cattle and unpasteurized dairy products) and human sources of tuberculosis disease...

..This article will focus on what the genome sequences of M. tuberculosis and M. leprae have taught us about these pathogens, and how comparative genomics has exposed some of the fundamental differences between the species...

..These compounds appear as promising specific antitubercular agents, since they exhibited neither significant cytotoxicity against mammal cells, nor effect on the growth of various bacteria and fungi...

..In the course of our future work, we will increase the potency of the next generation of PknB inhibitors in order to improve their antibacterial activity...

..leprae infection and epidemiological surveys of the incidence of leprosy, of which little is known...

..CFP-10 complex to be constructed that is critical for understanding the structure-function relationship in tuberculosis pathogenesis...