Novel rhamnosyltransferase involved in biosynthesis of serovar 4-specific glycopeptidolipid from Mycobacterium avium complex.
Glycopeptidolipids (GPLs) are one of the major glycolipid components present on the surface of Mycobacterium avium complex (MAC) that belong to opportunistic pathogens distributed in the natural environment. The serovars of MAC, up to around 30 types, are defined by the variable oligosaccharide portions of the GPLs. Epidemiological studies show that serovar 4 is the most prevalent type, and the prognosis of pulmonary disease caused by serovar 4 is significantly worse than that caused by other serovars. However, little is known about the biosynthesis of serovar 4-specific GPL, particularly the formation of the oligosaccharide portion that determines the properties of serovar 4. To investigate the biosynthesis of serovar 4-specific GPL, we focused on one segment that included functionally unknown genes in the GPL biosynthetic gene cluster of a serovar 4 strain. In this segment, a putative hemolytic protein gene, hlpA, and its downstream gene were found to be responsible for the formation of the 4-O-methyl-rhamnose residue, which is unique to serovar 4-specific GPL. Moreover, functional characterization of the hlpA gene revealed that it encodes a rhamnosyltransferase that transfers a rhamnose residue via 1→4 linkage to a fucose residue of serovar 2-specific GPL, which is a key pathway leading to the synthesis of oligosaccharide of serovar 4-specific GPL. These findings may provide clues to understanding the biological role of serovar 4-specific GPL in MAC pathogenicity and may also provide new insights into glycosyltransferase, which generates structural and functional diversity of GPLs.
Miyamoto
Yuji
Y
Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan. yujim@nih.go.jp
Mukai
Tetsu
T
Naka
Takashi
T
Fujiwara
Nagatoshi
N
Maeda
Yumi
Y
Kai
Masanori
M
Mizuno
Seiko
S
Yano
Ikuya
I
Makino
Masahiko
M
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002236:Carbohydrate Conformation; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006017:Glycolipids / Q000096:biosynthesis*; D006020:Glycopeptides / Q000096:biosynthesis*; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D015269:Mycobacterium avium Complex / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D012703:Serotyping
D001426:Bacterial Proteins; D006017:Glycolipids; D006020:Glycopeptides; D016695:Glycosyltransferases
J Bacteriol. 2007 Aug;189(15):5515-22
17526707
J Leukoc Biol. 2006 Aug;80(2):415-23
16760377
Int J Syst Bacteriol. 1993 Jul;43(3):482-9
8347508
FEMS Microbiol Lett. 2004 Jul 15;236(2):227-34
15251201
J Bacteriol. 2008 May;190(10):3613-21
18326570
J Clin Microbiol. 1990 May;28(5):926-9
2351735
J Clin Microbiol. 1992 Feb;30(2):479-84
1537920
J Clin Microbiol. 2005 Jul;43(7):3150-8
16000428
Cell Mol Life Sci. 2001 Dec;58(14):2018-42
11814054
Annu Rev Biochem. 1995;64:29-63
7574484
J Biol Chem. 2000 Aug 11;275(32):24900-6
10801784
Microbiology (Reading). 2002 Oct;148(Pt 10):3079-3087
12368441
Infect Immun. 1992 Feb;60(2):706-11
1730507
J Bacteriol. 1998 Nov;180(21):5567-73
9791104
APMIS. 1996 Apr;104(4):318-20
8645472
J Bacteriol. 1986 Nov;168(2):660-7
3782019
Infect Immun. 1995 Jan;63(1):126-33
7806348
Biol Pharm Bull. 2005 Feb;28(2):335-9
15684494
Adv Microb Physiol. 1998;39:131-203
9328647
J Biol Chem. 1987 Feb 25;262(6):2630-5
2434488
J Bacteriol. 2007 Feb;189(3):1099-108
17122347
Vet Microbiol. 2003 Feb 2;91(2-3):249-64
12458173
Oral Microbiol Immunol. 1999 Jun;14(3):143-52
10495708
Biochim Biophys Acta. 1983 May 16;751(3):439-43
6849953
J Clin Microbiol. 1994 Nov;32(11):2880-2
7852596
J Bacteriol. 2008 Dec;190(24):7918-24
18849433
Adv Carbohydr Chem Biochem. 1995;51:169-242
7484363
Microbiology (Reading). 2003 Oct;149(Pt 10):2797-2807
14523113
Front Biosci. 1998 Aug 05;3:d865-76
9693156
Infect Immun. 1999 Sep;67(9):4895-901
10456946
Mol Microbiol. 1990 Nov;4(11):1911-9
2082148
J Biol Chem. 2008 Nov 28;283(48):33221-31
18824550
J Biol Chem. 1993 May 15;268(14):10517-23
8486704
Microb Pathog. 2000 Jul;29(1):9-16
10873486