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Infection and Immunity, January 2001, p. 508-517, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.508-517.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Legionella pneumophila Entry Gene rtxA Is Involved in Virulence

Suat L. G. Cirillo,1 Luiz E. Bermudez,2 Sahar H. El-Etr,1 Gerald E. Duhamel,1 and Jeffrey D. Cirillo1,*

Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska 68583,1 and Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center, San Francisco, California 941152

Received 14 July 2000/Returned for modification 21 September 2000/Accepted 3 October 2000

Successful parasitism of host cells by intracellular pathogens involves adherence, entry, survival, intracellular replication, and cell-to-cell spread. Our laboratory has been examining the role of early events, adherence and entry, in the pathogenesis of the facultative intracellular pathogen Legionella pneumophila. Currently, the mechanisms used by L. pneumophila to gain access to the intracellular environment are not well understood. We have recently isolated three loci, designated enh1, enh2, and enh3, that are involved in the ability of L. pneumophila to enter host cells. One of the genes present in the enh1 locus, rtxA, is homologous to repeats in structural toxin genes (RTX) found in many bacterial pathogens. RTX proteins from other bacterial species are commonly cytotoxic, and some of them have been shown to bind to beta 2 integrin receptors. In the current study, we demonstrate that the L. pneumophila rtxA gene is involved in adherence, cytotoxicity, and pore formation in addition to its role in entry. Furthermore, an rtxA mutant does not replicate as well as wild-type L. pneumophila in monocytes and is less virulent in mice. Thus, we conclude that the entry gene rtxA is an important virulence determinant in L. pneumophila and is likely to be critical for the production of Legionnaires' disease in humans.

* Corresponding author. Mailing address: Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, 203 VBS, Fair and East Campus Loop, Lincoln, NE 68583. Phone: (402) 472-8587. Fax: (402) 472-9690. E-mail: jcirillo1{at}unl.edu.

Infection and Immunity, January 2001, p. 508-517, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.508-517.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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