This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00269-08v1 76/8/3577    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Russo, T. A. Articles by Campagnari, A. A. PubMed PubMed Citation Articles by Russo, T. A. Articles by Campagnari, A. A.

 Previous Article  |  Next Article 

Infection and Immunity, August 2008, p. 3577-3586, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00269-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rat Pneumonia and Soft-Tissue Infection Models for the Study of Acinetobacter baumannii Biology

Veterans Administration Western New York Healthcare System,¹ Department of Medicine,² Department of Microbiology,³ The Witebsky Center for Microbial Pathogenesis,⁴ Center of Excellence in Bioinformatics and Life Sciences,⁵ Department of Oral Biology, University at Buffalo-State University of New York, Buffalo, New York 14214⁶

Received 26 February 2008/ Accepted 28 May 2008

Acinetobacter baumannii is a bacterial pathogen of increasing medical importance. Little is known about its mechanisms of pathogenesis, and safe reliable agents with predictable activity against A. baumannii are presently nonexistent. The availability of relevant animal infection models will facilitate the study of Acinetobacter biology. In this report we tested the hypothesis that the rat pneumonia and soft-tissue infection models that our laboratory had previously used for studies of extraintestinal pathogenic Escherichia coli were clinically relevant for A. baumannii. Advantages of these models over previously described models were that the animals were not rendered neutropenic and they did not receive porcine mucin with bacterial challenge. Using the A. baumannii model pathogen 307-0294 as the challenge pathogen, the pneumonia model demonstrated all of the features of infection that are critical for a clinically relevant model: namely, bacterial growth/clearance, an ensuing host inflammatory response, acute lung injury, and, following progressive bacterial proliferation, death due to respiratory failure. We were also able to demonstrate growth of 307-0294 in the soft-tissue infection model. Next we tested the hypothesis that the soft-tissue infection model could be used to discriminate between the inherent differences in virulence of various A. baumannii clinical isolates. The ability of A. baumannii to grow and/or be cleared in this model was dependent on the challenge strain. We also hypothesized that complement is an important host factor in protecting against A. baumannii infection in vivo. In support of this hypothesis was the observation that the serum sensitivity of various A. baumannii clinical isolates in vitro roughly paralleled their growth/clearance in the soft-tissue infection model in vivo. Lastly we hypothesized that the soft-tissue infection model would serve as an efficient screening mechanism for identifying gene essentiality for drug discovery. Random mutants of 307-0294 were initially screened for lack of growth in human ascites in vitro. Selected mutants were subsequently used for challenge in the soft-tissue infection model to determine if the disrupted gene was essential for growth in vivo. Using this approach, we have been able to successfully identify a number of genes essential for the growth of 307-0294 in vivo. In summary, these models are clinically relevant and can be used to study the innate virulence of various Acinetobacter clinical isolates and to assess potential virulence factors, vaccine candidates, and drug targets in vivo and can be used for pharmacokinetic and chemotherapeutic investigations.

Published ahead of print on 9 June 2008.

Editor: V. J. DiRita