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Infection and Immunity, October 2007, p. 5035-5042, Vol. 75, No. 10
0019-9567/07/$08.00+0     doi:10.1128/IAI.00506-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Hemolysin and the Multifunctional Autoprocessing RTX Toxin Are Virulence Factors during Intestinal Infection of Mice with Vibrio cholerae El Tor O1 Strains{triangledown}

Verena Olivier,1 G. Kenneth Haines III,2,{dagger} Yanping Tan,1,{ddagger} and Karla J. Fullner Satchell1*

Department of Microbiology-Immunology,1 Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois2

Received 9 April 2007/ Returned for modification 20 June 2007/ Accepted 30 July 2007

The seventh cholera pandemic that started in 1961 was caused by Vibrio cholerae O1 strains of the El Tor biotype. These strains produce the pore-forming toxin hemolysin, a characteristic used clinically to distinguish classical and El Tor biotypes. Even though extensive in vitro data on the cytolytic activities of hemolysin exist, the connection of hemolysin to virulence in vivo is not well characterized. To study the contribution of hemolysin and other accessory toxins to pathogenesis, we utilized the model of intestinal infection in adult mice sensitive to the actions of accessory toxins. In this study, we showed that 4- to 6-week-old streptomycin-fed C57BL/6 mice were susceptible to intestinal infection with El Tor strains, which caused rapid death at high doses. Hemolysin had the predominant role in lethality, with a secondary contribution by the multifunctional autoprocessing RTX (MARTX) toxin. Cholera toxin and hemagglutinin/protease did not contribute to lethality in this model. Rapid death was not caused by increased dissemination due to a damaged epithelium since the numbers of CFU recovered from spleens and livers 6 h after infection did not differ between mice inoculated with hemolysin-expressing strains and those infected with non-hemolysin-expressing strains. Although accessory toxins were linked to virulence, a strain defective in the production of accessory toxins was still immunogenic since mice immunized with a multitoxin-deficient strain were protected from a subsequent lethal challenge with the wild type. These data suggest that hemolysin and MARTX toxin contribute to vaccine reactogenicity but that the genes for these toxins can be deleted from vaccine strains without affecting vaccine efficacy.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, Northwestern University, 303 E. Chicago Ave., Tarry 3-713, Chicago, IL 60611. Phone: (312) 503-2162. Fax: (312) 503-1339. E-mail: k-satchell{at}northwestern.edu

{triangledown} Published ahead of print on 13 August 2007.

Editor: V. J. DiRita

{dagger} Present address: Department of Pathology, Yale University School of Medicine, New Haven, CT.

{ddagger} Present address: Blood Research Institute, Blood Center of Wisconsin, Milwaukee.

Infection and Immunity, October 2007, p. 5035-5042, Vol. 75, No. 10
0019-9567/07/$08.00+0     doi:10.1128/IAI.00506-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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