Conversion of an extracellular cytolysin into a phagosome-specific lysin which supports the growth of an intracellular pathogen.

Abstract:

:Listeria monocytogenes is a facultative intracellular pathogen which secretes a pore-forming cytolysin, listeriolysin O (LLO), necessary for intracellular growth. Clostridium perfringens is an extracellular pathogen which secretes a related cytolysin, perfringolysin O (PFO). When PFO is secreted by intracellular L. monocytogenes, it is toxic to the infected host cell. PFO-mediated toxicity renders the infected host cell permeable to gentamicin and leads to the death of the intracellular bacteria. In this study, we selected for L. monocytogenes mutants in which PFO supported the intracellular growth of L. monocytogenes. Six independent mutants were isolated, each containing a single amino acid change within the PFO protein. Three classes of PFO mutations were identified, all capable of mediating lysis of the vacuole but without a toxic effect upon the infected host cell. The first class had a severe defect in haemolytic activity. The second class had a change in the pH optimum of PFO. The third class had nearly wild-type levels of haemolytic activity, but had a decrease in protein half-life in the host-cell cytosol. Acquisition of single amino acid changes in PFO were sufficient to convert an extracellular cytolysin into a vacuole-specific lysin which mediated growth of L. monocytogenes in cultured cells.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Jones S,Preiter K,Portnoy DA

doi

10.1046/j.1365-2958.1996.00074.x

subject

Has Abstract

pub_date

1996-09-01 00:00:00

pages

1219-25

issue

6

eissn

0950-382X

issn

1365-2958

journal_volume

21

pub_type

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