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

Tobias Sydor, Kristine von Bargen, Fong Fu Hsu, Gitta Huth, Otto Holst, Jens Wohlmann, Ulrike Becken, Tobias Dykstra, Kristina Söhl, Buko Lindner, John F. Prescott, Ulrich E. Schaible, Olaf Utermöhlen, Albert Haas

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Abstract

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 β-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.

Original languageEnglish
Pages (from-to)458-473
Number of pages16
JournalCellular microbiology
Volume15
Issue number3
DOIs
StatePublished - Mar 2013

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    Sydor, T., von Bargen, K., Hsu, F. F., Huth, G., Holst, O., Wohlmann, J., Becken, U., Dykstra, T., Söhl, K., Lindner, B., Prescott, J. F., Schaible, U. E., Utermöhlen, O., & Haas, A. (2013). Diversion of phagosome trafficking by pathogenic Rhodococcus equi depends on mycolic acid chain length. Cellular microbiology, 15(3), 458-473. https://doi.org/10.1111/cmi.12050