Genomics of glycopeptidolipid biosynthesis in Mycobacterium abscessus and M. chelonae.
BACKGROUND
The outermost layer of the bacterial surface is of crucial importance because it is in constant interaction with the host. Glycopeptidolipids (GPLs) are major surface glycolipids present on various mycobacterial species. In the fast-grower model organism Mycobacterium smegmatis, GPL biosynthesis involves approximately 30 genes all mapping to a single region of 65 kb.


RESULTS
We have recently sequenced the complete genomes of two fast-growers causing human infections, Mycobacterium abscessus (CIP 104536T) and M. chelonae (CIP 104535T). We show here that these two species contain genes corresponding to all those of the M. smegmatis "GPL locus", with extensive conservation of the predicted protein sequences consistent with the production of GPL molecules indistinguishable by biochemical analysis. However, the GPL locus appears to be split into several parts in M. chelonae and M. abscessus. One large cluster (19 genes) comprises all genes involved in the synthesis of the tripeptide-aminoalcohol moiety, the glycosylation of the lipopeptide and methylation/acetylation modifications. We provide evidence that a duplicated acetyltransferase (atf1 and atf2) in M. abscessus and M. chelonae has evolved through specialization, being able to transfer one acetyl at once in a sequential manner. There is a second smaller and distant (M. chelonae, 900 kb; M. abscessus, 3 Mb) cluster of six genes involved in the synthesis of the fatty acyl moiety and its attachment to the tripeptide-aminoalcohol moiety. The other genes are scattered throughout the genome, including two genes encoding putative regulatory proteins.


CONCLUSIONS
Although these three species produce identical GPL molecules, the organization of GPL genes differ between them, thus constituting species-specific signatures. An hypothesis is that the compact organization of the GPL locus in M. smegmatis represents the ancestral form and that evolution has scattered various pieces throughout the genome in M. abscessus and M. chelonae.
Ripoll
Fabienne
F
Laboratoire de Microbiologie, Université de Versailles Saint-Quentin-en-Yvelines, Faculté de Médecine de Paris-Ile de France-Ouest, F-92380 Garches, France. ripoll.f@libertysurf.fr <ripoll.f@libertysurf.fr>
Deshayes
Caroline
C
Pasek
Sophie
S
Laval
Françoise
F
Beretti
Jean-Luc
JL
Biet
Franck
F
Risler
Jean-Loup
JL
Daffé
Mamadou
M
Etienne
Gilles
G
Gaillard
Jean-Louis
JL
Reyrat
Jean-Marc
JM
D000123:Acetyltransferases / Q000235:genetics; D001483:Base Sequence; D053898:Biosynthetic Pathways / Q000235:genetics*; D002855:Chromatography, Thin Layer; D019143:Evolution, Molecular; D016680:Genome, Bacterial / Q000235:genetics*; D006017:Glycolipids / Q000096:biosynthesis / Q000235:genetics*; D006020:Glycopeptides / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D016926:Mycobacterium chelonae / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D006017:Glycolipids; D006020:Glycopeptides; D000123:Acetyltransferases