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Infection and Immunity, February 2000, p. 999-1003, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Role of Listeriolysin O in Cell-to-Cell Spread of Listeria monocytogenes

Margaret M. Gedde,1,dagger Darren E. Higgins,1,Dagger Lewis G. Tilney,2 and Daniel A. Portnoy1,*

Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, California 94720-3202,1 and Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-60182

Received 28 May 1999/Returned for modification 20 August 1999/Accepted 21 October 1999

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a host vacuolar compartment and grows rapidly in the cytosol. Listeriolysin O (LLO) is a secreted pore-forming protein essential for the escape of L. monocytogenes from the vacuole formed upon initial internalization. However, its role in intracellular growth and cell-to-cell spread events has not been testable by a genetic approach. In this study, purified six-His-tagged LLO (HisLLO) was noncovalently coupled to the surface of nickel-treated LLO-negative mutants. Bound LLO mediated vacuolar escape in approximately 2% of the mutants. After 5.5 h of growth, cytosolic bacteria were indistinguishable from wild-type bacteria with regard to formation of pseudopod-like extensions, here termed listeriopods, and spread to adjacent cells. However, bacteria in adjacent cells failed to multiply and were found in double-membrane vacuoles. Addition of bound LLO to mutants lacking LLO and two distinct phospholipases C (PLCs) also resulted in spread to adjacent cells, but these triple mutants became trapped in multiple-membrane vacuoles that are reminiscent of autophagocytic vacuoles. These studies show that neither LLO nor the PLCs are necessary for listeriopod formation and uptake of bacteria into neighboring cells but that LLO is required for the escape of L. monocytogenes from the double-membrane vacuole that forms upon cell-to-cell spread.

* Corresponding author. Mailing address: University of California, Department of Molecular & Cell Biology/401 Barker Hall, Berkeley, CA 94720-3202. Phone: (510) 643-3925. Fax: (510) 643-5035. E-mail: portnoy{at}uclink4.berkeley.edu.

dagger Present address: IntraBiotics Pharmaceuticals, Inc., Mountain View, CA 94043.

Dagger Present address: Department of Microbiology & Molecular Genetics, Harvard Medical School, Boston, MA 02115.

Infection and Immunity, February 2000, p. 999-1003, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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