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Infection and Immunity, February 2007, p. 581-591, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.00997-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Mycobacterial Gene Involved in Synthesis of an Outer Cell Envelope Lipid Is a Key Factor in Prevention of Phagosome Maturation

Institute for Medical Microbiology, Immunology and Hygiene,¹ Institute of Pathology, University of Cologne, 50935 Cologne, Germany²

Received 23 June 2006/ Returned for modification 7 August 2006/ Accepted 26 October 2006

Virulent mycobacteria cause arrest of phagosome maturation as a part of their survival strategy in hosts. This process is mediated through multiple virulence factors, whose molecular nature remains elusive. Using Mycobacterium marinum as a model, we performed a genome-wide screen to identify mutants whose ability to inhibit phagosome maturation was impaired, and we succeeded in isolating a comprehensive set of mutants that were not able to occupy an early endosome-like phagosomal compartment in mammalian macrophages. Categorizing and ordering the multiple mutations according to their gene families demonstrated that the genes modulating the cell envelope are the principal factors in arresting phagosome maturation. In particular, we identified a novel gene, pmiA, which is capable of influencing the constitution of the cell envelope lipids, thereby leading to the phagosome maturation block. The pmiA mutant was not able to resist phagosome maturation and was severely attenuated in mice. Complementing the mutant with the wild-type gene restored the attenuated virulence to wild-type levels in mice.

Published ahead of print on 6 November 2006.

Editor: J. L. Flynn

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