title: Expression analysis of a highly adherent and cytotoxic small colony variant of Pseudomonas aeruginosa isolated from a lung of a patient with cystic fibrosis.
abstract: 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.
authors.affiliation: Institute of Medical Microbiology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany. steinmetz.ivo@mh-hannover.de
authors.forename: Franz
authors.initials: F
authors.lastname: von Götz
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
authors.forename: Doris
authors.initials: D
authors.lastname: Jordan
authors.forename: Senthil Selvan
authors.initials: SS
authors.lastname: Saravanamuthu
authors.forename: Dirk
authors.initials: D
authors.lastname: Wehmhöner
authors.forename: André
authors.initials: A
authors.lastname: Strüssmann
authors.forename: Joerg
authors.initials: J
authors.lastname: Lauber
authors.forename: Ina
authors.initials: I
authors.lastname: Attree
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tümmler
authors.forename: Ivo
authors.initials: I
authors.lastname: Steinmetz
mesh_terms: 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
chemical_list: D001426:Bacterial Proteins; D020543:Proteome