Diversion of phagosome trafficking by pathogenic Rhodococcus equi depends on mycolic acid chain length

作者：Sydor Tobias; von Bargen Kristine; Hsu Fong Fu; Huth Gitta; Holst Otto; Wohlmann Jens; Becken Ulrike; Dykstra Tobias; Soehl Kristina; Lindner Buko; Prescott John F; Schaible Ulrich E; Utermoehlen Olaf; Haas Albert^*

来源：Cellular Microbiology, 2013, 15(3): 458-473.

DOI：10.1111/cmi.12050

Rhodococcus equi is a close relative of Mycobacterium spp. and a facultative intracellular pathogen which arrests phagosome maturation in macrophages before the late endocytic stage. We have screened a transposon mutant library of R.equi for mutants with decreased capability to prevent phagolysosome formation. This screen yielded a mutant in the gene for -ketoacyl-(acyl carrier protein)-synthase A (KasA), a key enzyme of the long-chain mycolic acid synthesizing FAS-II system. The longest kasA mutant mycolic acid chains were 10 carbon units shorter than those of wild-type bacteria. Coating of non-pathogenic E.coli with purified wild-type trehalose dimycolate reduced phagolysosome formation substantially which was not the case with shorter kasA mutant-derived trehalose dimycolate. The mutant was moderately attenuated in macrophages and in a mouse infection model, but was fully cytotoxic.Whereas loss of KasA is lethal in mycobacteria, R.equi kasA mutant multiplication in broth was normal proving that long-chain mycolic acid compounds are not necessarily required for cellular integrity and viability of the bacteria that typically produce them. This study demonstrates a central role of mycolic acid chain length in diversion of trafficking by R.equi.

• 出版日期2013-3