Biochemistry
Article
phthiocerol dimycocerosate and the attenuation indicator lipid. Infect.
Immun. 9, 150−158.
(7) Cox, J. S., Chen, B., McNeil, M., and Jacobs, W. R., Jr. (1999)
Complex lipid determines tissue-specific replication of Mycobacterium
tuberculosis in mice. Nature 402, 79−83.
(8) Camacho, L. R., Ensergueix, D., Perez, E., Gicquel, B., and
Guilhot, C. (1999) Identification of a virulence gene cluster of
Mycobacterium tuberculosis by signature-tagged transposon muta-
genesis. Mol. Microbiol. 34, 257−267.
(22) Bhatt, K., Gurcha, S. S., Bhatt, A., Besra, G. S., and Jacobs, W. R.
(2007) Two polyketide-synthase-associated acyltransferases are
required for sulfolipid biosynthesis in Mycobacterium tuberculosis.
Microbiology 153, 513−520.
(23) Hatzios, S. K., Schelle, M. W., Holsclaw, C. M., Behrens, C. R.,
Botyanszki, Z., Lin, F. L., Carlson, B. L., Kumar, P., Leary, J. A., and
Bertozzi, C. R. (2009) PapA3 is an acyltransferase required for
Polyacyltrehalose biosynthesis in Mycobacterium tuberculosis. J. Biol.
Chem. 284, 12745−12751.
(24) Jain, M., Petzold, C. J., Schelle, M. W., Leavell, M. D., Mougous,
J. D., Bertozzi, C. R., Leary, J. A., and Cox, J. S. (2007) Lipidomics
reveals control of Mycobacterium tuberculosis virulence lipids via
metabolic coupling. Proc. Natl. Acad. Sci. U. S. A. 104, 5133−5138.
(25) Yang, X., Nesbitt, N. M., Dubnau, E., Smith, I., and Sampson, N.
S. (2009) Cholesterol Metabolism Increases the Metabolic Pool of
Propionate in Mycobacterium tuberculosis. Biochemistry 48, 3819−
3821.
(26) Singh, A., Crossman, D. K., Mai, D., Guidry, L., Voskuil, M. I.,
Renfrow, M. B., and Steyn, A. J. C. (2009) Mycobacterium tuberculosis
WhiB3Maintains Redox Homeostasis by Regulating Virulence Lipid
Anabolism to Modulate Macrophage Response. PLoS Pathog. 5,
e1000545.
(27) Shi, L., Sohaskey, C. D., Kana, B. D., Dawes, S., North, R. J.,
Mizrahi, V., and Gennaro, M. L. (2005) Changes in energy metabolism
of Mycobacterium tuberculosis in mouse lung and under in vitro
conditions affecting aerobic respiration. Proc. Natl. Acad. Sci. U. S. A.
102, 15629−15634.
(28) Rohde, K. H., Veiga, D. F., Caldwell, S., Balazsi, G., and Russell,
D. G. (2012) Linking the transcriptional profiles and the physiological
states of Mycobacterium tuberculosis during an extended intracellular
infection. PLoS Pathog. 8, e1002769.
(29) Gomez-Velasco, A., Bach, H., Rana, A. K., Cox, L. R., Bhatt, A.,
Besra, G. S., and Av-Gay, Y. (2013) Disruption of the serine/threonine
protein kinase H affects phthiocerol dimycocerosates synthesis in
Mycobacterium tuberculosis. Microbiology 159, 726−736.
(30) Perez, J., Garcia, R., Bach, H., de Waard, J. H., Jacobs, W. R., Jr.,
Av-Gay, Y., Bubis, J., and Takiff, H. E. (2006) Mycobacterium
tuberculosis transporter MmpL7 is a potential substrate for kinase
PknD. Biochem. Biophys. Res. Commun. 348, 6−12.
(31) Gupta, M., Sajid, A., Arora, G., Tandon, V., and Singh, Y. (2009)
Forkhead-associated domain-containing protein Rv0019c and polyke-
tide-associated protein PapA5, from substrates of serine/threonine
protein kinase PknB to interacting proteins of Mycobacterium
tuberculosis. J. Biol. Chem. 284, 34723−34734.
(32) Prisic, S., Dankwa, S., Schwartz, D., Chou, M. F., Locasale, J. W.,
Kang, C. M., Bemis, G., Church, G. M., Steen, H., and Husson, R. N.
(2010) Extensive phosphorylation with overlapping specificity by
Mycobacterium tuberculosis serine/threonine protein kinases. Proc.
Natl. Acad. Sci. U. S. A. 107, 7521−7526.
(33) Fortuin, S., Tomazella, G. G., Nagaraj, N., Sampson, S. L., Gey
van Pittius, N. C., Soares, N. C., Wiker, H. G., de Souza, G. A., and
Warren, R. M. (2015) Phosphoproteomics analysis of a clinical
Mycobacterium tuberculosis Beijing isolate: expanding the mycobac-
terial phosphoproteome catalog. Front. Microbiol. 6, 6.
(9) Yu, J., Tran, V., Li, M., Huang, X., Niu, C., Wang, D., Zhu, J.,
Wang, J., Gao, Q., and Liu, J. (2012) Both phthiocerol dimycocer-
osates and phenolic glycolipids are required for virulence of
Mycobacterium marinum. Infect. Immun. 80, 1381−1389.
(10) Rousseau, C., Winter, N., Pivert, E., Bordat, Y., Neyrolles, O.,
́
Ave, P., Huerre, M., Gicquel, B., and Jackson, M. (2004) Production of
phthiocerol dimycocerosates protects Mycobacterium tuberculosis
from the cidal activity of reactive nitrogen intermediates produced
by macrophages and modulates the early immune response to
infection. Cell. Microbiol. 6, 277−287.
(11) Murry, J. P., Pandey, A. K., Sassetti, C. M., and Rubin, E. J.
(2009) Phthiocerol Dimycocerosate Transport Is Required for
Resisting Interferon-γ−Independent Immunity. J. Infect. Dis. 200,
774−782.
́
(12) Kirksey, M. A., Tischler, A. D., Simeone, R., Hisert, K. B.,
Uplekar, S., Guilhot, C., and McKinney, J. D. (2011) Spontaneous
Phthiocerol Dimycocerosate-Deficient Variants of Mycobacterium
tuberculosis Are Susceptible to Gamma Interferon-Mediated Im-
munity. Infect. Immun. 79, 2829−2838.
(13) Cambier, C. J., Takaki, K. K., Larson, R. P., Hernandez, R. E.,
Tobin, D. M., Urdahl, K. B., Cosma, C. L., and Ramakrishnan, L.
(2014) Mycobacteria manipulate macrophage recruitment through
coordinated use of membrane lipids. Nature 505, 218−222.
(14) Quadri, L. E. (2014) Biosynthesis of mycobacterial lipids by
polyketide synthases and beyond. Crit. Rev. Biochem. Mol. Biol. 49,
179−211.
(15) Vergnolle, O., Chavadi, S. S., Edupuganti, U. R., Mohandas, P.,
Chan, C., Zeng, J., Kopylov, M., Angelo, N. G., Warren, J. D., Soll, C.
E., and Quadri, L. E. (2015) Biosynthesis of mycobacterial cell-
envelope-associated phenolic glycolipids in Mycobacterium marinum.
J. Bacteriol. 197, 1040−1050.
(16) Chavadi, S. S., Onwueme, K. C., Edupuganti, U. R., Jerome, J.,
Chatterjee, D., Soll, C. E., and Quadri, L. E. N. (2012) The
mycobacterial acyltransferase PapA5 is required for biosynthesis of cell
wall-associated phenolic glycolipids. Microbiology 158, 1379−1387.
(17) Onwueme, K. C., Ferreras, J. A., Buglino, J., Lima, C. D., and
Quadri, L. E. N. (2004) Mycobacterial polyketide-associated proteins
are acyltransferases: Proof of principle with Mycobacterium tuber-
culosis PapA5. Proc. Natl. Acad. Sci. U. S. A. 101, 4608−4613.
(18) Buglino, J., Onwueme, K. C., Ferreras, J. A., Quadri, L. E. N.,
and Lima, C. D. (2004) Crystal Structure of PapA5, a Phthiocerol
Dimycocerosyl Transferase from Mycobacterium tuberculosis. J. Biol.
Chem. 279, 30634−30642.
(19) Camacho, L. R., Constant, P., Raynaud, C., Laneelle, M. A.,
Triccas, J. A., Gicquel, B., Daffe, M., and Guilhot, C. (2001) Analysis of
the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis.
Evidence that this lipid is involved in the cell wall permeability barrier.
J. Biol. Chem. 276, 19845−19854.
(20) Sulzenbacher, G., Canaan, S., Bordat, Y., Neyrolles, O.,
Stadthagen, G., Roig-Zamboni, V., Rauzier, J., Maurin, D., Laval, F.,
Daffe, M., Cambillau, C., Gicquel, B., Bourne, Y., and Jackson, M.
́
(2006) LppX is a lipoprotein required for the translocation of
phthiocerol dimycocerosates to the surface of Mycobacterium tuber-
culosis. EMBO J. 25, 1436−1444.
(21) Kumar, P., Schelle, M. W., Jain, M., Lin, F. L., Petzold, C. J.,
Leavell, M. D., Leary, J. A., Cox, J. S., and Bertozzi, C. R. (2007)
PapA1 and PapA2 are acyltransferases essential for the biosynthesis of
Mycobacterium tuberculosis virulence factor Sulfolipid-1. Proc. Natl.
Acad. Sci. U. S. A. 104, 11221−11226.
(34) Molle, V., Gulten, G., Vilcheze, C., Veyron-Churlet, R., Zanella-
Cleon, I., Sacchettini, J. C., Jacobs, W. R., Jr., and Kremer, L. (2010)
Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth
of Mycobacterium tuberculosis. Mol. Microbiol. 78, 1591−1605.
(35) Corrales, R. M., Molle, V., Leiba, J., Mourey, L., de Chastellier,
C., and Kremer, L. (2012) Phosphorylation of mycobacterial PcaA
inhibits mycolic acid cyclopropanation: consequences for intracellular
survival and for phagosome maturation block. J. Biol. Chem. 287,
26187−26199.
(36) Vilcheze, C., Molle, V., Carrere-Kremer, S., Leiba, J., Mourey, L.,
Shenai, S., Baronian, G., Tufariello, J., Hartman, T., Veyron-Churlet,
R., Trivelli, X., Tiwari, S., Weinrick, B., Alland, D., Guerardel, Y.,
Jacobs, W. R., Jr., and Kremer, L. (2014) Phosphorylation of KasB
Regulates Virulence and Acid-Fastness in Mycobacterium tuberculosis.
PLoS Pathog. 10, e1004115.
K
Biochemistry XXXX, XXX, XXX−XXX