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Updated: May 26, 2026
Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
PcrV antibody-antibiotic combination improves survival in Pseudomonas aeruginosa-infected mice
1Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA. song.yuanlin@zs-hospital.sh.cn
Abstract:
The type III secretion system (TTSS) of Pseudomonas aeruginosa, associated with acute infection, facilitates the direct injection of cytotoxins into the host cell cytoplasm. Mab166, a murine monoclonal antibody against PcrV, a protein located at the tip of the injectisome, has demonstrated efficacy against P. aeruginosa infection, resulting in reduced lung injury and increased survival in murine models of infection. We hypothesised that the administration of Mab166 in combination with an antibiotic would further improve the survival of P. aeruginosa-infected mice. A murine model of P. aeruginosa acute infection, three clinically relevant antibiotics (ciprofloxacin, tobramycin and ceftazidime) and the Mab166 antibody were used for this study. Consistently, compared to other treatment groups (antibiotic or antibody administered in isolation), the combination of Mab166 and antibiotic significantly improved the survival of mice infected with three times the lethal dose (LD(90)) of the highly cytotoxic ExoU-secreting strain, PA103. This synergistic effect was primarily due to enhanced bactericidal effect and protection against lung injury, which prevented bacterial dissemination to other organs. Hence, the combination of Mab166 with antibiotic administration provides a new, more effective strategy against P. aeruginosa airway infection, especially when large numbers of highly virulent strains are present.
Insights
Combining Mab166 antibody with antibiotics significantly improves survival in mice with Pseudomonas aeruginosa infections. This strategy enhances bacterial killing and reduces lung injury, offering a potent approach against severe airway infections.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa utilizes the type III secretion system (TTSS) to inject cytotoxins into host cells, causing acute infections.
- The anti-PcrV monoclonal antibody Mab166 shows efficacy against P. aeruginosa by reducing lung injury and improving survival in murine models.
- The PcrV protein is a key component located at the tip of the TTSS injectisome.
Purpose of the Study:
- To investigate the synergistic effect of combining Mab166 with antibiotics against P. aeruginosa infection.
- To evaluate the impact of this combination therapy on survival rates and lung pathology in a murine model.
Main Methods:
- A murine model of acute P. aeruginosa infection was established using the highly cytotoxic strain PA103 (ExoU-secreting).
- Mice were treated with either Mab166, clinically relevant antibiotics (ciprofloxacin, tobramycin, ceftazidime), or a combination of Mab166 and antibiotic.
- Survival rates, bactericidal effects, and lung injury were assessed in all treatment groups.
Main Results:
- The combination of Mab166 and antibiotics significantly improved mouse survival compared to monotherapy when challenged with a high dose (3x LD(90)) of PA103.
- This synergistic effect was attributed to enhanced bactericidal activity and substantial protection against lung injury.
- Reduced lung injury prevented systemic bacterial dissemination to other organs.
Conclusions:
- Combination therapy with Mab166 and antibiotics presents a more effective strategy for treating P. aeruginosa airway infections.
- This approach is particularly beneficial in cases involving highly virulent strains and high bacterial loads.
- The enhanced bactericidal effect and organ protection underscore the potential of this combined therapeutic strategy.
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