alexa Virulence Factors Involved in Passage of Francisella tularensis subsp. novicida Through an Air-Blood Barrier Model | OMICS International | Abstract
ISSN: 2157-2526

Journal of Bioterrorism & Biodefense
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Research Article

Virulence Factors Involved in Passage of Francisella tularensis subsp. novicida Through an Air-Blood Barrier Model

Sandra S. Ojeda1, Chris A. Mares2, Jorge I. Alvarez3, Qun Li4, Carlos J. Orihuela2 and Judy M. Teale2,4*

1Department of Immunology UT MD Anderson Cancer Center 7455 Fannin Houston, TX, 77030, USA

2Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio 7703 Floyd Curl Dr. San Antonio, TX, 78229, USA

3Neuroimmunology unit, Neurosciences Centre Hospitalier De L’Université de Montréal - Hôpital Notre Dame 2099 Alexandre de Seve, Y3608 Montreal, QC H2L 2W5

4Department of Biology, University of Texas at San Antonio One UTSA Circle San Antonio, TX, 78249, USA

*Corresponding Author:
Judy M. Teale Ph.D
Department of Biology-MBT
University of Texas at San Antonio
One UTSA Circle, San Antonio, TX 78249
Tel: 210-458-7024
Fax: 210-458-7025
E-mail: [email protected]

Received Date: June 24, 2011; Accepted Date: November 08, 2011; Published Date: November 17, 2011

Citation: Ojeda SS, Mares CA, Alvarez JI, Li Q, Orihuela CJ, et al. (2011) Virulence Factors Involved in Passage of Francisella tularensis subsp. novicida Through an Air-Blood Barrier Model. J Bioterr Biodef S3:003. doi: 10.4172/2157-2526.S3-003

Copyright: © 2011 Ojeda SS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Francisella tularensis subsp. novicida ( F. novicida ) is a facultative intracellular pathogen that when inhaled causes respiratory infection in mice; it is widely used as a model to study tularemia caused by F. tularensis. F. novicida is able to infect different cell types including macrophages and dendritic cells. In the present study we examined F. novicida interactions with human lung epithelial cells and determined the role of established virulence determinants in these processes. A549 type II lung epithelial cells and murine LA-4 bronchial epithelial cells were used to examine the ability of wild type F. novicida and the mutant F. novicida strains deficient in IglC, Tul4, MglA, 58kDa membrane lipoprotein, and RipA to adhere, invade, replicate within, and translocate through an in vitro transwell system. Using this systematic approach, we determined that different virulence factors play cell-site specific roles during infection: Tul4 is important for adhesion to lung cells; MglA, 58kDa protein, and Tul4 are important for cell invasion; IglC and its transcriptional regulator MglA are important for intracellular replication; and the function of MglA is required for migration across cell barriers. In addition we also determined that F. novicida infection results in upregulation of matrix metalloprotease 9 (MMP-9) by lung epithelial cells and the subsequent disruption of cell adherens junctions as characterized by loss of cadherin, alpha and beta catenin, and the basal membrane protein laminin.

We conclude that F. novicida is able to attach, invade, and cross through lung epithelial cells and that these properties are determined by individual virulence determinants.

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