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Journal of Bacteriology, June 2004, p. 3837-3847, Vol. 186, No. 12
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.12.3837-3847.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Expression Analysis of a Highly Adherent and Cytotoxic Small Colony Variant of Pseudomonas aeruginosa Isolated from a Lung of a Patient with Cystic Fibrosis{dagger}

Franz von Götz,1,2 Susanne Häussler,1 Doris Jordan,1 Senthil Selvan Saravanamuthu,1 Dirk Wehmhöner,1,3 André Strüßmann,1 Joerg Lauber,3 Ina Attree,4 Jan Buer,1,3 Burkhard Tümmler,2 and Ivo Steinmetz1*

Institute of Medical Microbiology,1 Department of Pediatric Pneumology, Hannover Medical School, 30625 Hannover,2 German Research Centre for Biotechnology, 38124 Braunschweig, Germany,3 Biochimie et Biophysique des Systèmes Intégrés (UMR-5092 CNRS/CEA/UJF), DBMS, CEA, 38054 Grenoble Cedex 09, France4

Received 4 November 2003/ Accepted 3 March 2004

The heterogeneous environment of the lung of the cystic fibrosis (CF) patient gives rise to Pseudomonas aeruginosa small colony variants (SCVs) with increased antibiotic resistance, autoaggregative growth behavior, and an enhanced ability to form biofilms. In this study, oligonucleotide DNA microarrays were used to perform a genome-wide expression study of autoaggregative and highly adherent P. aeruginosa SCV 20265 isolated from a CF patient's lung in comparison with its clonal wild type and a revertant generated in vitro from the SCV population. Most strikingly, SCV 20265 showed a pronounced upregulation of the type III protein secretion system (TTSS) and the respective effector proteins. This differential expression was shown to be biologically meaningful, as SCV 20265 and other hyperpiliated and autoaggregative SCVs with increased TTSS expression were significantly more cytotoxic for macrophages in vitro and were more virulent in a mouse model of respiratory tract infection than the wild type. The observed cytotoxicity and virulence of SCV 20265 required exsA, an important transcriptional activator of the TTSS. Thus, the prevailing assumption that P. aeruginosa is subject to selection towards reduced cytotoxicity and attenuated virulence during chronic CF lung infection might not apply to all clonal variants.

* Corresponding author. Mailing address: Institute of Medical Microbiology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany. Phone: (49) 511-5324352. Fax: (49) 511-5324366. E-mail: steinmetz.ivo{at}mh-hannover.de.

{dagger} Supplemental material for this article may be found at http://jb.asm.org.

Journal of Bacteriology, June 2004, p. 3837-3847, Vol. 186, No. 12
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.12.3837-3847.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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