Nonmucoid Pseudomonas aeruginosa expresses alginate in the lungs of patients with cystic fibrosis and in a mouse model.
BACKGROUND
In patients with cystic fibrosis (CF), lung infection with mucoid Pseudomonas aeruginosa strains overexpressing the exopolysaccaride alginate is preceded by colonization with nonmucoid strains. We investigated the kinetics, impact of environmental signals, and genetics of P. aeruginosa alginate expression in a mouse model and in patients with CF.


METHODS
Using indirect immunofluorescence, microarray technology and real-time reverse-transcription polymerase chain reaction, we assessed alginate gene expression during aerobic and anaerobic growth of the nonmucoid strain PAO1 in vitro, in a mouse lung-infection model and in sputum specimens from patients with CF infected with nonmucoid or mucoid P. aeruginosa strains.


RESULTS
Anaerobic conditions increased the transcription of alginate genes in vitro and in murine lungs within 24 h. Alginate production by PAO1 in murine lungs and by nonmucoid P. aeruginosa strains in patients with CF was reversible after in vitro culture under aerobic conditions. A subpopulation of P. aeruginosa clones revealing stable alginate production was detected in murine lungs 2 weeks after infection.


CONCLUSIONS
Anaerobiosis and lung infection rapidly induce alginate production by gene regulation in nonmucoid P. aeruginosa. This trait may contribute to early persistence, leading to chronic P. aeruginosa infection once stable mucoid strains are generated.
Institute of Medical Microbiology and Hygiene, Universitatsklinikum Tubingen, Germany.
Alessandra
A
Bragonzi
Dieter
D
Worlitzsch
Gerald B
GB
Pier
Petra
P
Timpert
Martina
M
Ulrich
Morten
M
Hentzer
Jens Bo
JB
Andersen
Michael
M
Givskov
Massimo
M
Conese
Gerd
G
Doring
D000464:Alginates / Q000378:metabolism*; D000818:Animals; D001441:Bacteroides fragilis / Q000378:metabolism; D003550:Cystic Fibrosis / Q000382:microbiology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000382:microbiology*; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D013183:Sputum / Q000382:microbiology
D000464:Alginates