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Journal of Bacteriology, December 2008, p. 7918-7924, Vol. 190, No. 24
0021-9193/08/$08.00+0     doi:10.1128/JB.00911-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Mycobacterium avium Complex gtfTB Gene Encodes a Glucosyltransferase Required for the Biosynthesis of Serovar 8-Specific Glycopeptidolipid{triangledown}

Yuji Miyamoto,1* Tetsu Mukai,1 Yumi Maeda,1 Masanori Kai,1 Takashi Naka,2 Ikuya Yano,2 and Masahiko Makino1

Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan,1 Japan BCG Central Laboratory, 3-1-5 Matsuyama, Kiyose, Tokyo 204-0022, Japan2

Received 2 July 2008/ Accepted 29 September 2008

Mycobacterium avium complex (MAC) is one of the most common opportunistic pathogens widely distributed in the natural environment. The 28 serovars of MAC are defined by variable oligosaccharide portions of glycopeptidolipids (GPLs) that are abundant on the surface of the cell envelope. These GPLs are also known to contribute to the virulence of MAC. Serovar 8 is one of the dominant serovars isolated from AIDS patients, but the biosynthesis of serovar 8-specific GPL remains unknown. To clarify this, we compared gene clusters involved in the biosynthesis of several serovar-specific GPLs and identified the genomic region predicted to be responsible for GPL biosynthesis in a serovar 8 strain. Sequencing of this region revealed the presence of four open reading frames, three unnamed genes and gtfTB, the function of which has not been elucidated. The simultaneous expression of gtfTB and two downstream genes in a recombinant Mycobacterium smegmatis strain genetically modified to produce serovar 1-specific GPL resulted in the appearance of 4,6-O-(1-carboxyethylidene)-3-O-methyl-glucose, which is unique to serovar 8-specific GPL, suggesting that these three genes participate in its biosynthesis. Furthermore, functional analyses of gtfTB indicated that it encodes a glucosyltransferase that transfers a glucose residue via 1->3 linkage to a rhamnose residue of serovar 1-specific GPL, which is critical to the formation of the oligosaccharide portion of serovar 8-specific GPL. Our findings might provide a clue to understanding the biosynthetic regulation that modulates the biological functions of GPLs in MAC.

* Corresponding author. Mailing address: Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan. Phone: 81-42-391-8211. Fax: 81-42-394-9092. E-mail: yujim{at}nih.go.jp

{triangledown} Published ahead of print on 10 October 2008.

Journal of Bacteriology, December 2008, p. 7918-7924, Vol. 190, No. 24
0021-9193/08/$08.00+0     doi:10.1128/JB.00911-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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