Mycolyltransferase-mediated glycolipid exchange in Mycobacteria.
Trehalose dimycolate (TDM), also known as cord factor, is a major surface glycolipid of the cell wall of mycobacteria. Because of its potent biological functions in models of infection, adjuvancy, and immunotherapy, it is important to determine how its biosynthesis is regulated. Here we show that glucose, a host-derived product that is not readily available in the environment, causes Mycobacterium avium to down-regulate TDM expression while up-regulating production of another major glycolipid with immunological roles in T cell activation, glucose monomycolate (GMM). In vitro, the mechanism of reciprocal regulation of TDM and GMM involves competitive substrate selection by antigen 85A. The switch from TDM to GMM biosynthesis occurs near the physiological concentration of glucose present in mammalian hosts. We further demonstrate that GMM is produced in vivo by mycobacteria growing in mouse lung. These results establish an enzymatic pathway for GMM production. More generally, these observations provide a specific enzymatic mechanism for dynamic alterations of cell wall glycolipid remodeling in response to the transition from noncellular to cellular growth environments, including factors that are monitored by the host immune system.
Matsunaga
Isamu
I
Laboratory of Cell Regulation, Institute for Virus Research, Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan.
Naka
Takashi
T
Talekar
Rahul S
RS
McConnell
Matthew J
MJ
Katoh
Kumiko
K
Nakao
Hitomi
H
Otsuka
Atsushi
A
Behar
Samuel M
SM
Yano
Ikuya
I
Moody
D Branch
DB
Sugita
Masahiko
M
D000217:Acyltransferases / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D004926:Escherichia coli / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006017:Glycolipids / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008213:Lymphocyte Activation; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009164:Mycobacterium Infections / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011994:Recombinant Proteins / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism
D006017:Glycolipids; D008055:Lipids; D011994:Recombinant Proteins; D000217:Acyltransferases; C053820:trehalose mycolyltransferase