Expression analysis of a highly adherent and cytotoxic small colony variant of Pseudomonas aeruginosa isolated from a lung of a patient with cystic fibrosis.
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.
von Götz
Franz
F
Institute of Medical Microbiology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany. steinmetz.ivo@mh-hannover.de
Häussler
Susanne
S
Jordan
Doris
D
Saravanamuthu
Senthil Selvan
SS
Wehmhöner
Dirk
D
Strüssmann
André
A
Lauber
Joerg
J
Attree
Ina
I
Buer
Jan
J
Tümmler
Burkhard
B
Steinmetz
Ivo
I
D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms; D002460:Cell Line; D003550:Cystic Fibrosis / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000145:classification / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D020543:Proteome