The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids

被引：15

作者：

Chavadi, Sivagami Sundaram ^{[1
]}

Onwueme, Kenolisa C. ^{[2
]}

Edupuganti, Uthamaphani R. ^{[1
]}

Jerome, Jeff ^{[1
]}

Chatterjee, Delphi ^{[3
]}

Soll, Clifford E. ^{[4
]}

Quadri, Luis E. N. ^{[1
]}

机构：

[1] CUNY Brooklyn Coll, Dept Biol, Brooklyn, NY 11210 USA

[2] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA

[3] Colorado State Univ, Coll Vet Med & Biomed Sci, Microbiol Immunol & Pathol Dept, Ft Collins, CO 80523 USA

[4] CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA

来源：

MICROBIOLOGY-SGM | 2012年 / 158卷

关键词：

SIGNATURE-TAGGED MUTAGENESIS; SMALL-MOLECULE INHIBITION; CYTOKINE RESPONSE; VIRULENCE FACTORS; GENE-CLUSTER; TUBERCULOSIS; IDENTIFICATION; STRAINS; MARINUM; LEPRAE;

D O I：

10.1099/mic.0.057869-0

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Phenolic glycolipids (PGLs) are non-covalently bound components of the outer membrane of many clinically relevant mycobacterial pathogens, and play important roles in pathogen biology. We report a mutational analysis that conclusively demonstrates that the conserved acyltransferase-encoding gene papA5 is essential for PGL production. In addition, we provide an in vitro acyltransferase activity analysis that establishes proof of principle for the competency of PapA5 to utilize diol-containing polyketide compounds of mycobacterial origin as acyl-acceptor substrates. Overall, the results reported herein are in line with a model in which PapA5 catalyses the acylation of diol-containing polyketides to form PGLs. These studies advance our understanding of the biosynthesis of an important group of mycobacterial glycolipids and suggest that PapA5 might be an attractive target for exploring the development of antivirulence drugs.

引用

页码：1379 / 1387

页数：9

共 36 条

[1] A Mycobacterium marinum TesA mutant defective for major cell wall-associated lipids is highly attenuated in Dictyostelium discoideum and zebrafish embryos [J].

Alibaud, Laeticia ;

Rombouts, Yoann ;

Trivelli, Xavier ;

Burguiere, Adeline ;

Cirillo, Suat L. G. ;

Cirillo, Jeffrey D. ;

Dubremetz, Jean-Francois ;

Guerardel, Yann ;

Lutfalla, Georges ;

Kremer, Laurent .

MOLECULAR MICROBIOLOGY, 2011, 80 (04) :919-934

[2] Phthiocerol Dimycocerosates of M. tuberculosis Participate in Macrophage Invasion by Inducing Changes in the Organization of Plasma Membrane Lipids [J].

Astarie-Dequeker, Catherine ;

Le Guyader, Laurent ;

Malaga, Wladimir ;

Seaphanh, Fam-Ky ;

Chalut, Christian ;

Lopez, Andre ;

Guilhot, Christophe .

PLOS PATHOGENS, 2009, 5 (02)

[3]

BRENNAN PJ, 1994, METHOD ENZYMOL, V242, P27

[4] THE ENVELOPE OF MYCOBACTERIA [J].

BRENNAN, PJ ;

NIKAIDO, H .

ANNUAL REVIEW OF BIOCHEMISTRY, 1995, 64 :29-63

[5] High Content Phenotypic Cell-Based Visual Screen Identifies Mycobacterium tuberculosis Acyltrehalose-Containing Glycolipids Involved in Phagosome Remodeling [J].

Brodin, Priscille ;

Poquet, Yannick ;

Levillain, Florence ;

Peguillet, Isabelle ;

Larrouy-Maumus, Gerald ;

Gilleron, Martine ;

Ewann, Fanny ;

Christophe, Thierry ;

Fenistein, Denis ;

Jang, Jichan ;

Jang, Mi-Seon ;

Park, Sei-Jin ;

Rauzier, Jean ;

Carralot, Jean-Philippe ;

Shrimpton, Rachel ;

Genovesio, Auguste ;

Gonzalo-Asensio, Jesus A. ;

Puzo, Germain ;

Martin, Carlos ;

Brosch, Roland ;

Stewart, Graham R. ;

Gicquel, Brigitte ;

Neyrolles, Olivier .

PLOS PATHOGENS, 2010, 6 (09)

[6] Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis [J].

Buglino, J ;

Onwueme, KC ;

Ferreras, JA ;

Quadri, LEN ;

Lima, CD .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (29) :30634-30642

[7] Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis [J].

Camacho, LR ;

Ensergueix, D ;

Perez, E ;

Gicquel, B ;

Guilhot, C .

MOLECULAR MICROBIOLOGY, 1999, 34 (02) :257-267

[8] Mutational and Phylogenetic Analyses of the Mycobacterial mbt Gene Cluster [J].

Chavadi, Sivagami Sundaram ;

Stirrett, Karen L. ;

Edupuganti, Uthamaphani R. ;

Vergnolle, Olivia ;

Sadhanandan, Gigani ;

Marchiano, Emily ;

Martin, Che ;

Qiu, Wei-Gang ;

Soll, Clifford E. ;

Quadri, Luis E. N. .

JOURNAL OF BACTERIOLOGY, 2011, 193 (21) :5905-5913

[9] Inactivation of tesA Reduces Cell Wall Lipid Production and Increases Drug Susceptibility in Mycobacteria [J].

Chavadi, Sivagami Sundaram ;

Edupuganti, Uthamaphani R. ;

Vergnolle, Olivia ;

Fatima, Itrat ;

Singh, Shaneen M. ;

Soll, Clifford E. ;

Quadri, Luis E. N. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (28) :24616-24625

[10] Generation of attenuated Mycobacterium bovis strains by signature-tagged mutagenesis for discovery of novel vaccine candidates [J].

Collins, DM ;

Skou, B ;

White, S ;

Bassett, S ;

Collins, L ;

For, R ;

Hurr, K ;

Hotter, G ;

de Lisle, GW .

INFECTION AND IMMUNITY, 2005, 73 (04) :2379-2386

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