Etienne Gilles, Malaga Wladimir, Laval Françoise, Lemassu Anne, Guilhot Christophe, Daffé Mamadou
CNRS, Institut de Pharmacologie et de Biologie Structurale, Département Mécanismes Moléculaires des Infections Mycobactériennes, 205 route de Narbonne, F-31077 Toulouse, France.
J Bacteriol. 2009 Apr;191(8):2613-21. doi: 10.1128/JB.01235-08. Epub 2009 Jan 30.
Lipooligosaccharides (LOS) are highly antigenic glycolipids produced by a number of Mycobacterium species, which include "M. canettii," a member of the M. tuberculosis complex, and the opportunistic pathogens M. marinum and M. kansasii. The various LOS share a core composed of trehalose esterified by at least 1 mole of polymethyl-branched fatty acid (PMB-FA) and differ from one another by their oligosaccharide extensions. In this study, we identified a cluster of genes, MSMEG_4727 through MSMEG_4741, likely involved in the synthesis of LOS in M. smegmatis. Disruption of MSMEG_4727 (the ortholog of pks5 of M. tuberculosis), which encodes a putative polyketide synthase, resulted in the concomitant abrogation of the production of both PMB-FA and LOS in the mutant strain. Complementation of the mutant with the wild-type gene fully restored the phenotype. We also showed that, in contrast to the case for "M. canettii" and M. marinum, LOS are located in deeper compartments of the cell envelope of M. smegmatis. The availability of two mycobacterial strains differing only in LOS production should help in defining the biological role(s) of this important glycolipid.
脂寡糖（LOS）是由多种分枝杆菌属物种产生的高度抗原性糖脂，这些物种包括结核分枝杆菌复合群的成员“堪氏分枝杆菌”以及机会性病原菌海分枝杆菌和堪萨斯分枝杆菌。各种LOS共享一个由海藻糖组成的核心，该海藻糖被至少1摩尔的多甲基支链脂肪酸（PMB - FA）酯化，并且它们彼此之间的区别在于其寡糖延伸部分。在本研究中，我们鉴定出了一组基因，即耻垢分枝杆菌中的MSMEG_4727至MSMEG_4741，它们可能参与了耻垢分枝杆菌中LOS的合成。编码假定聚酮合酶的MSMEG_4727（结核分枝杆菌pks5的直系同源物）的破坏导致突变菌株中PMB - FA和LOS的产生同时被消除。用野生型基因对突变体进行互补完全恢复了表型。我们还表明，与“堪氏分枝杆菌”和海分枝杆菌的情况不同，LOS位于耻垢分枝杆菌细胞包膜的更深层区室中。两种仅在LOS产生方面存在差异的分枝杆菌菌株的可得性应有助于确定这种重要糖脂的生物学作用。
