Immunogenicity and antimicrobial effectiveness of Pseudomonas aeruginosa specific bacteriophage in a human lung in
Joseph R Shiley1, Kristen K Comfort2, Jayne B Robinson3
1Department of Biology, University of Dayton, Dayton, OH, 45469, USA.
Abstract:
The rise of antibiotic resistant bacteria is posing a serious threat to human health. For example, resistant strains of Pseudomonas aeruginosa have resulted in untreatable and potentially lethal infections in both cystic fibrosis and immunocompromised patients. Due to the growing need for alternative treatment options, bacteriophage, or phage, therapy is gaining considerable attention. While previous studies have demonstrated the effectiveness of phage in combating persistent bacterial infections, there is currently a lack of knowledge regarding the host immunological response following phage exposure. In the present study, the bioresponses of an enhanced in vitro model were characterized following exposure to either DMS3 or PEV2, P. aeruginosa targeting phages. Results demonstrated a PEV2-dependent increase in IL-6 and TNF-α production, but no changes associated with DMS3 exposure. Additionally, following the establishment of an in vitro infection model, DMS3 was found to successfully protect mammalian lung cells from P. aeruginosa. Taken together, the biocompatibility and antibacterial effectiveness distinguish DMS3 bacteriophage as a strong candidate for phage therapy. However, as DMS3 is pilin dependent and bacterial receptor expression varies significantly, this work highlights the necessity of generating phage cocktails.
Insights
Bacteriophage therapy shows promise against antibiotic-resistant Pseudomonas aeruginosa. DMS3 bacteriophage protected lung cells and showed biocompatibility, unlike PEV2 which triggered an immune response, suggesting phage cocktails are necessary.
Area of Science:
- Microbiology
- Immunology
- Biotechnology
Background:
- Antibiotic-resistant bacteria, like Pseudomonas aeruginosa, pose a significant health threat.
- Bacteriophage therapy is an emerging alternative to antibiotics.
- Understanding the host immune response to bacteriophages is crucial for therapeutic development.
Purpose of the Study:
- To characterize the in vitro bioresponses to P. aeruginosa-targeting bacteriophages DMS3 and PEV2.
- To evaluate the protective efficacy of DMS3 against P. aeruginosa in a mammalian lung cell model.
Main Methods:
- An enhanced in vitro model was used to assess host bioresponses (IL-6, TNF-α).
- A P. aeruginosa infection model in mammalian lung cells was established.
- Bacteriophage efficacy and host response were measured.
Main Results:
- PEV2 bacteriophage exposure increased IL-6 and TNF-α production.
- DMS3 bacteriophage exposure did not significantly alter IL-6 or TNF-α levels.
- DMS3 successfully protected mammalian lung cells from P. aeruginosa infection.
Conclusions:
- DMS3 bacteriophage demonstrates biocompatibility and antibacterial effectiveness, making it a candidate for phage therapy.
- The pilin-dependent nature of DMS3 and variable bacterial receptor expression necessitate the development of phage cocktails.
