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Infection and Immunity, March 2003, p. 1405-1415, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1405-1415.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Attenuated Virulence of a Burkholderia cepacia Type III Secretion Mutant in a Murine Model of Infection

Mladen Tomich,1 Adam Griffith,2 Christine A. Herfst,1 Jane L. Burns,2 and Christian D. Mohr1*

Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455,1 Division of Pediatric Infectious Disease, Children's Hospital and Regional Medical Center, Seattle, Washington 981052

Received 10 July 2002/ Returned for modification 23 September 2002/ Accepted 3 December 2002

Type III secretion systems are utilized by a number of gram-negative bacterial pathogens to deliver virulence-associated proteins into host cells. Using a PCR-based approach, we identified homologs of type III secretion genes in the gram-negative bacterium Burkholderia cepacia, an important pulmonary pathogen in immunocompromised patients and patients with cystic fibrosis. One of the genes, designated bscN, encodes a member of a family of ATP-binding proteins believed to generate energy driving virulence protein secretion. Genetic dissection of the regions flanking the bscN gene revealed a locus consisting of at least 10 open reading frames, predicted to encode products with significant homology to known type III secretion proteins in other bacteria. A defined null mutation was generated in the bscN gene, and the null strain and wild-type parent strain were examined by use of a murine model of B. cepacia infection. Quantitative bacteriological analysis of the lungs and spleens of infected C57BL/6 mice revealed that the bscN null strain was attenuated in virulence compared to the parent strain, with significantly lower bacterial recovery from the lungs and spleens at 3 days postinfection. Moreover, histopathological changes, including an inflammatory cell infiltrate, were more pronounced in the lungs of mice infected with the wild-type parent strain than in those of mice infected with the isogenic bscN mutant. These results implicate type III secretion as an important determinant in the pathogenesis of B. cepacia.

* Corresponding author. Mailing address: Department of Microbiology, University of Minnesota, Minneapolis, MN 55455-0312. Phone: (612) 625-7104. Fax: (612) 626-0623. E-mail: mohr{at}mail.ahc.umn.edu.

Editor: V. J. DiRita

Infection and Immunity, March 2003, p. 1405-1415, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1405-1415.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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