Frigui W

References (4)

Title : Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis - Supply_2013_Nat.Genet_45_172
Author(s) : Supply P , Marceau M , Mangenot S , Roche D , Rouanet C , Khanna V , Majlessi L , Criscuolo A , Tap J , Pawlik A , Fiette L , Orgeur M , Fabre M , Parmentier C , Frigui W , Simeone R , Boritsch EC , Debrie AS , Willery E , Walker D , Quail MA , Ma L , Bouchier C , Salvignol G , Sayes F , Cascioferro A , Seemann T , Barbe V , Locht C , Gutierrez MC , Leclerc C , Bentley SD , Stinear TP , Brisse S , Medigue C , Parkhill J , Cruveiller S , Brosch R
Ref : Nat Genet , 45 :172 , 2013
Abstract : Global spread and limited genetic variation are hallmarks of M. tuberculosis, the agent of human tuberculosis. In contrast, Mycobacterium canettii and related tubercle bacilli that also cause human tuberculosis and exhibit unusual smooth colony morphology are restricted to East Africa. Here, we sequenced and analyzed the whole genomes of five representative strains of smooth tubercle bacilli (STB) using Sanger (4-5x coverage), 454/Roche (13-18x coverage) and/or Illumina DNA sequencing (45-105x coverage). We show that STB isolates are highly recombinogenic and evolutionarily early branching, with larger genome sizes, higher rates of genetic variation, fewer molecular scars and distinct CRISPR-Cas systems relative to M. tuberculosis. Despite the differences, all tuberculosis-causing mycobacteria share a highly conserved core genome. Mouse infection experiments showed that STB strains are less persistent and virulent than M. tuberculosis. We conclude that M. tuberculosis emerged from an ancestral STB-like pool of mycobacteria by gain of persistence and virulence mechanisms, and we provide insights into the molecular events involved.
ESTHER : Supply_2013_Nat.Genet_45_172
PubMedSearch : Supply_2013_Nat.Genet_45_172
PubMedID: 23291586
Gene_locus related to this paper: mycmm-b2ht49 , myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-Rv1069c , myctu-RV1215C , myctu-RV1758 , myctu-Rv2045c , myctu-RV3452 , myctu-RV3724 , myctu-Rv3802c

Title : Genome plasticity of BCG and impact on vaccine efficacy - Brosch_2007_Proc.Natl.Acad.Sci.U.S.A_104_5596
Author(s) : Brosch R , Gordon SV , Garnier T , Eiglmeier K , Frigui W , Valenti P , Dos Santos S , Duthoy S , Lacroix C , Garcia-Pelayo C , Inwald JK , Golby P , Garcia JN , Hewinson RG , Behr MA , Quail MA , Churcher C , Barrell BG , Parkhill J , Cole ST
Ref : Proc Natl Acad Sci U S A , 104 :5596 , 2007
Abstract : To understand the evolution, attenuation, and variable protective efficacy of bacillus Calmette-Guerin (BCG) vaccines, Mycobacterium bovis BCG Pasteur 1173P2 has been subjected to comparative genome and transcriptome analysis. The 4,374,522-bp genome contains 3,954 protein-coding genes, 58 of which are present in two copies as a result of two independent tandem duplications, DU1 and DU2. DU1 is restricted to BCG Pasteur, although four forms of DU2 exist; DU2-I is confined to early BCG vaccines, like BCG Japan, whereas DU2-III and DU2-IV occur in the late vaccines. The glycerol-3-phosphate dehydrogenase gene, glpD2, is one of only three genes common to all four DU2 variants, implying that BCG requires higher levels of this enzyme to grow on glycerol. Further amplification of the DU2 region is ongoing, even within vaccine preparations used to immunize humans. An evolutionary scheme for BCG vaccines was established by analyzing DU2 and other markers. Lesions in genes encoding sigma-factors and pleiotropic transcriptional regulators, like PhoR and Crp, were also uncovered in various BCG strains; together with gene amplification, these affect gene expression levels, immunogenicity, and, possibly, protection against tuberculosis. Furthermore, the combined findings suggest that early BCG vaccines may even be superior to the later ones that are more widely used.
ESTHER : Brosch_2007_Proc.Natl.Acad.Sci.U.S.A_104_5596
PubMedSearch : Brosch_2007_Proc.Natl.Acad.Sci.U.S.A_104_5596
PubMedID: 17372194
Gene_locus related to this paper: myctu-a85a , myctu-a85b , myctu-a85c , myctu-bpoC , myctu-cut3 , myctu-cutas2 , myctu-d5yk66 , myctu-ephB , myctu-ephc , myctu-ephd , myctu-ephE , myctu-hpx , myctu-linb , myctu-lipG , myctu-lipJ , myctu-LIPS , myctu-lipv , myctu-LPQC , myctu-LPQP , myctu-MBTB , myctu-metx , myctu-mpt51 , myctu-MT1628 , myctu-p71654 , myctu-p95011 , myctu-PKS6 , myctu-PKS13 , myctu-ppe42 , myctu-ppe63 , myctu-Rv1430 , myctu-RV0045C , myctu-Rv0077c , myctu-Rv0151c , myctu-Rv0152c , myctu-Rv0159c , myctu-Rv0160c , myctu-rv0183 , myctu-Rv0217c , myctu-Rv0220 , myctu-Rv0272c , myctu-RV0293C , myctu-RV0457C , myctu-RV0519C , myctu-RV0774C , myctu-RV0782 , myctu-RV0840C , myctu-Rv1069c , myctu-Rv1076 , myctu-RV1123C , myctu-Rv1184c , myctu-Rv1191 , myctu-RV1192 , myctu-RV1215C , myctu-Rv1399c , myctu-Rv1400c , myctu-Rv1426c , myctu-RV1639C , myctu-RV1683 , myctu-RV1758 , myctu-Rv1800 , myctu-Rv1833c , myctu-Rv2045c , myctu-RV2054 , myctu-Rv2284 , myctu-RV2296 , myctu-Rv2385 , myctu-Rv2485c , myctu-RV2627C , myctu-RV2672 , myctu-RV2695 , myctu-RV2765 , myctu-RV2800 , myctu-RV2854 , myctu-Rv2970c , myctu-Rv3084 , myctu-Rv3097c , myctu-rv3177 , myctu-Rv3312c , myctu-RV3452 , myctu-RV3473C , myctu-Rv3487c , myctu-Rv3569c , myctu-Rv3591c , myctu-RV3724 , myctu-Rv3802c , myctu-Rv3822 , myctu-y0571 , myctu-y963 , myctu-Y1834 , myctu-y1835 , myctu-y2079 , myctu-yc88 , myctu-ym23 , myctu-ym24 , myctu-YR15 , myctu-yt28

Title : Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer - Stinear_2007_Genome.Res_17_192
Author(s) : Stinear TP , Seemann T , Pidot S , Frigui W , Reysset G , Garnier T , Meurice G , Simon D , Bouchier C , Ma L , Tichit M , Porter JL , Ryan J , Johnson PD , Davies JK , Jenkin GA , Small PL , Jones LM , Tekaia F , Laval F , Daffe M , Parkhill J , Cole ST
Ref : Genome Res , 17 :192 , 2007
Abstract : Mycobacterium ulcerans is found in aquatic ecosystems and causes Buruli ulcer in humans, a neglected but devastating necrotic disease of subcutaneous tissue that is rampant throughout West and Central Africa. Here, we report the complete 5.8-Mb genome sequence of M. ulcerans and show that it comprises two circular replicons, a chromosome of 5632 kb and a virulence plasmid of 174 kb. The plasmid is required for production of the polyketide toxin mycolactone, which provokes necrosis. Comparisons with the recently completed 6.6-Mb genome of Mycobacterium marinum revealed >98% nucleotide sequence identity and genome-wide synteny. However, as well as the plasmid, M. ulcerans has accumulated 213 copies of the insertion sequence IS2404, 91 copies of IS2606, 771 pseudogenes, two bacteriophages, and multiple DNA deletions and rearrangements. These data indicate that M. ulcerans has recently evolved via lateral gene transfer and reductive evolution from the generalist, more rapid-growing environmental species M. marinum to become a niche-adapted specialist. Predictions based on genome inspection for the production of modified mycobacterial virulence factors, such as the highly abundant phthiodiolone lipids, were confirmed by structural analyses. Similarly, 11 protein-coding sequences identified as M. ulcerans-specific by comparative genomics were verified as such by PCR screening a diverse collection of 33 strains of M. 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.
ESTHER : Stinear_2007_Genome.Res_17_192
PubMedSearch : Stinear_2007_Genome.Res_17_192
PubMedID: 17210928
Gene_locus related to this paper: mycmm-b2hds9 , mycmm-b2hg81 , mycmm-b2hgg2 , mycmm-b2hj55 , mycmm-b2hju3 , mycmm-b2hlr0 , mycmm-b2hlv2 , mycmm-b2hq96 , mycmm-b2hsm8 , mycmr-q5sdq4 , myctu-RV1683 , mycua-a0pkg7 , mycua-a0pki1 , mycua-a0pkn2 , mycua-a0pkn5 , mycua-a0pku2 , mycua-a0pl47 , mycua-a0plr3 , mycua-a0plu8 , mycua-a0ply4 , mycua-a0pm12 , mycua-a0pm14 , mycua-a0pme3 , mycua-a0pmj6 , mycua-a0pml9 , mycua-a0pmv0 , mycua-a0pmx9 , mycua-a0pn71 , mycua-a0png7 , mycua-a0png9 , mycua-a0pp56 , mycua-a0ppm6 , mycua-a0pqm2 , mycua-a0pqs2 , mycua-a0pr64 , mycua-a0pr98 , mycua-a0prq2 , mycua-a0prr7 , mycua-a0psb1 , mycua-a0psb4 , mycua-a0psi2 , mycua-a0psi3 , mycua-a0psu3 , mycua-a0pt08 , mycua-a0pt71 , mycua-a0pth6 , mycua-a0ptq0 , mycua-a0pu55 , mycua-a0pum4 , mycua-a0pv11 , mycua-a0pv36 , mycua-a0pv77 , mycua-a0pva4 , mycua-a0pwi8 , mycua-a0pwm4 , mycua-a0pwr6 , mycua-a0pwz5 , mycua-a0px52 , mycua-metx , mycua-a0pmc2 , mycua-a0pvg7 , mycua-a0pwz4 , mycmm-b2hqy3 , mycua-a0pmc3

Title : Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans - Stinear_2004_Proc.Natl.Acad.Sci.U.S.A_101_1345
Author(s) : Stinear TP , Mve-Obiang A , Small PL , Frigui W , Pryor MJ , Brosch R , Jenkin GA , Johnson PD , Davies JK , Lee RE , Adusumilli S , Garnier T , Haydock SF , Leadlay PF , Cole ST
Ref : Proc Natl Acad Sci U S A , 101 :1345 , 2004
Abstract : Mycobacterium ulcerans (MU), an emerging human pathogen harbored by aquatic insects, is the causative agent of Buruli ulcer, a devastating skin disease rife throughout Central and West Africa. Mycolactone, an unusual macrolide with cytotoxic and immunosuppressive properties, is responsible for the massive s.c. tissue destruction seen in Buruli ulcer. Here, we show that MU contains a 174-kb plasmid, pMUM001, bearing a cluster of genes encoding giant polyketide synthases (PKSs), and polyketide-modifying enzymes, and demonstrate that these are necessary and sufficient for mycolactone synthesis. This is a previously uncharacterized example of plasmid-mediated virulence in a Mycobacterium, and the emergence of MU as a pathogen most likely reflects the acquisition of pMUM001 by horizontal transfer. The 12-membered core of mycolactone is produced by two giant, modular PKSs, MLSA1 (1.8 MDa) and MLSA2 (0.26 MDa), whereas its side chain is synthesized by MLSB (1.2 MDa), a third modular PKS highly related to MLSA1. There is an extreme level of sequence identity within the different domains of the MLS cluster (>97% amino acid identity), so much so that the 16 ketosynthase domains seem functionally identical. This is a finding of significant consequence for our understanding of polyketide biochemistry. 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.
ESTHER : Stinear_2004_Proc.Natl.Acad.Sci.U.S.A_101_1345
PubMedSearch : Stinear_2004_Proc.Natl.Acad.Sci.U.S.A_101_1345
PubMedID: 14736915