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Biofilm formation by Pseudomonas aeruginosa in solid murine tumors - a novel model system
Uliana Komor1, Piotr Bielecki, Holger Loessner
1Molecular Immunology, Helmholtz Center for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany. uliana.komor@helmholtz-hzi.de
Abstract:
The ability of opportunistic bacterial pathogens to grow in biofilms is decisive in the pathogenesis of chronic infectious diseases. Growth within biofilms does not only protect the bacteria against the host immune system but also from the killing by antimicrobial agents. Here, we introduce a mouse model in which intravenously administered planktonic Pseudomonas aeruginosa bacteria are enriched in transplantable subcutaneous mouse tumors. Electron microscopy images provide evidence that such bacteria reside in the tumor tissue within biofilm structures. Immunohistology furthermore demonstrated that infection of the tumor tissue elicits a host response characterized by strong neutrophilic influx. Interestingly, the biofilm defective PA14 pqsA transposon mutant formed less biofilm in vivo and was more susceptible to clearance by intravenous ciprofloxacin treatment as compared to the wild-type control. In conclusion, we have established an experimentally tractable model that may serve to identify novel bacterial and host factors important for in vivo biofilm formation and to re-evaluate bactericidal and anti-biofilm effects of currently used and novel antibacterial compounds.
Insights
This study establishes a new mouse model for studying Pseudomonas aeruginosa biofilms in tumors. The model shows that biofilm-defective mutants are more easily cleared by antibiotics, aiding anti-biofilm drug development.
Area of Science:
- Microbiology
- Pathogenesis
- Infectious Diseases
Background:
- Bacterial biofilms are crucial in chronic infections, protecting pathogens from host defenses and antimicrobials.
- Opportunistic pathogens like Pseudomonas aeruginosa form biofilms, complicating treatment.
Purpose of the Study:
- To develop a tractable mouse model for studying in vivo bacterial biofilm formation within tumors.
- To investigate the role of biofilms in Pseudomonas aeruginosa pathogenesis and antibiotic susceptibility.
Main Methods:
- Intravenous administration of planktonic Pseudomonas aeruginosa into subcutaneous mouse tumors.
- Analysis of bacterial biofilm structures using electron microscopy.
- Assessment of host immune response via immunohistology.
- Comparison of wild-type and biofilm-defective mutant susceptibility to ciprofloxacin.
Main Results:
- Pseudomonas aeruginosa successfully colonized and formed biofilms within mouse tumors.
- Tumor infection triggered a significant host neutrophilic influx.
- A biofilm-defective mutant (PA14 pqsA) exhibited reduced in vivo biofilm formation.
- The mutant strain was more susceptible to clearance by ciprofloxacin treatment compared to wild-type.
Conclusions:
- A novel, experimentally tractable mouse tumor model for in vivo biofilm studies has been established.
- This model can identify bacterial and host factors influencing biofilm formation.
- The model is useful for re-evaluating the efficacy of antibacterial and anti-biofilm compounds.
