Contribution of Veillonella parvula to Pseudomonas aeruginosa-mediated pathogenicity in a murine tumor model system.
The recent finding that high numbers of strict anaerobes are present in the respiratory tract of cystic fibrosis (CF) patients has drawn attention to the pathogenic contribution of the CF microbiome to airway disease. In this study, we investigated the specific interactions of the most dominant bacterial CF pathogen, Pseudomonas aeruginosa, with the anaerobic bacterium Veillonella parvula, which has been recovered at comparable cell numbers from the respiratory tract of CF patients. In addition to growth competition experiments, transcriptional profiling, and analyses of biofilm formation by in vitro studies, we used our recently established in vivo murine tumor model to investigate mutual influences of the two pathogens during a biofilm-associated infection process. We found that P. aeruginosa and V. parvula colonized distinct niches within the tumor. Interestingly, significantly higher cell numbers of P. aeruginosa could be recovered from the tumor tissue when mice were coinfected with both bacterial species than when mice were monoinfected with P. aeruginosa. Concordantly, the results of in vivo transcriptional profiling implied that the presence of V. parvula supports P. aeruginosa growth at the site of infection in the host, and the higher P. aeruginosa load correlated with clinical deterioration of the host. Although many challenges must be overcome to dissect the specific interactions of coinfecting bacteria during an infection process, our findings exemplarily demonstrate that the complex interrelations between coinfecting microorganisms and the immune responses determine clinical outcome to a much greater extent than previously anticipated.
Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute of Molecular Bacteriology, TWINCORE GmbH, Hannover, Germany.
Christian
C
Pustelny
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Uliana
U
Komor
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Vinay
V
Pawar
Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute of Molecular Bacteriology, TWINCORE GmbH, Hannover, Germany.
Anne
A
Lorenz
Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute of Molecular Bacteriology, TWINCORE GmbH, Hannover, Germany.
Agata
A
Bielecka
Biofilmcenter, German Heart Institute Berlin, Berlin, Germany.
Annette
A
Moter
Biofilmcenter, German Heart Institute Berlin, Berlin, Germany.
Benjamin
B
Gocht
Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute of Molecular Bacteriology, TWINCORE GmbH, Hannover, Germany.
Denitsa
D
Eckweiler
Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute of Molecular Bacteriology, TWINCORE GmbH, Hannover, Germany.
Mathias
M
Müsken
Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany.
Claudia
C
Grothe
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Heinrich
H
Lünsdorf
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Siegfried
S
Weiss
Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute of Molecular Bacteriology, TWINCORE GmbH, Hannover, Germany susanne.haeussler@helmholtz-hzi.de.
Susanne
S
Häussler
D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D008807:Mice, Inbred BALB C; D056265:Microbial Interactions; D009369:Neoplasms / Q000150:complications / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D014678:Veillonella / Q000472:pathogenicity*