Selection of transposon mutants of Mycobacterium tuberculosis with increased macrophage infectivity identifies fadD23 to be involved in sulfolipid production and association with macrophages

Lynett, Jennifer; Stokes, Richard W.

doi:10.1099/mic.0.2007/007864-0

Cited by 32 publications

(20 citation statements)

References 44 publications

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“…Lynett et al . have reported that this protein is involved in sulpholipid production and that disruption of the gene results in increased association between bacteria and macrophages [28]. Molina et al .…”

Section: Resultsmentioning

confidence: 99%

Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

Orduña

Cevallos

León³

et al. 2011

BMC Genomics

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BackgroundStudies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico.ResultsBCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks Region of Difference 1 (RD1), RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01), 655 (RDMex02) and 2,847 bp (REDMex03) long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests.ConclusionsBCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03). The loss of RDMex02 (fadD23) is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time.

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Section: Resultsmentioning

confidence: 99%

Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

Orduña

Cevallos

León³

et al. 2011

BMC Genomics

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“…Our present knowledge indicates that sulfation of trehalose, catalyzed by the sulfotransferase Stf0, is the fi rst step in SGL synthesis ( 26 ). Palmitate or stearate acyl chains derive from fatty-acid synthase-I (FAS-I), whereas HA and HPA are synthesized by polyketide synthase 2 (Pks2) ( 27 ) working in conjunction with the FadD23 fattyacyl-CoA ligase ( 28,29 ). Then, two acyl-transferases, PapA1 on one hand and PapA2 associated with Pks2 on the other hand, would act sequentially ( 25,30 ), where PapA2 converts sulfated trehalose into 2-palmitoyl/stearoyl-sulfated trehalose, and PapA1 further elaborates Ac 2 SGL by adding a methyl-branched fatty acid on the 3-position of trehalose.…”

Section: Discussionmentioning

confidence: 99%

Deciphering sulfoglycolipids of Mycobacterium tuberculosis

Layre

Paepe

Larrouy-Maumus

et al. 2011

Journal of Lipid Research

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“…The acyltransferase PapA2 then transfers a palmitoyl or stearoyl chain from palmitoyl- or stearoyl-CoA on the 2’-position of trehalose yielding a monoacylated SL (Kumar et al ., 2007; Bhatt et al ., 2007). The polyketide synthase Pks2 is responsible for the synthesis of phthioceranates and hydroxyphthioceranates using an activated fatty acid starter unit provided by the fatty acyl-AMP-ligase FadD23 (Sirakova et al ., 2001; Lynett and Stokes, 2007). Upon elongation by Pks2, a (hydroxy)phthioceranyl chain is then transferred to the 3’-position of trehalose by the acyltransferase PapA1, yielding a diacylated SL also known as SL 1278 (Kumar et al ., 2007; Bhatt et al ., 2007).…”

Section: The Major Cell Envelope Glycoconjugates Of Mtbmentioning

confidence: 99%

The cell envelope glycoconjugates ofMycobacterium tuberculosis

Angala

Belardinelli

Huc-Claustre

et al. 2014

Critical Reviews in Biochemistry and Molecular Biology

132

191

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Tuberculosis (TB) remains the second most common cause of death due to a single infectious agent. The cell envelope of Mycobacterium tuberculosis (Mtb), the causative agent of the disease in humans, is a source of unique glycoconjugates and the most distinctive feature of the biology of this organism. It is the basis of much of Mtb pathogenesis and one of the major causes of its intrinsic resistance to chemotherapeutic agents. At the same time, the unique structures of Mtb cell envelope glycoconjugates, their antigenicity and essentiality for mycobacterial growth provide opportunities for drug, vaccine, diagnostic and biomarker development, as clearly illustrated by recent advances in all of these translational aspects. This review focuses on our current understanding of the structure and biogenesis of Mtb glycoconjugates with particular emphasis on one of most intriguing and least understood aspect of the physiology of mycobacteria: the translocation of these complex macromolecules across the different layers of the cell envelope. It further reviews the rather impressive progress made in the last ten years in the discovery and development of novel inhibitors targeting their biogenesis.

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Selection of transposon mutants of Mycobacterium tuberculosis with increased macrophage infectivity identifies fadD23 to be involved in sulfolipid production and association with macrophages

Cited by 32 publications

References 44 publications

Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection

Deciphering sulfoglycolipids of Mycobacterium tuberculosis

The cell envelope glycoconjugates ofMycobacterium tuberculosis

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