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Updated: Oct 31, 2025
A Non-invasive and Technically Non-intensive Method for Induction and Phenotyping of Experimental Bacterial Pneumonia in Mice
Published on: September 28, 2016
Priming with intranasal lactobacilli prevents Pseudomonas aeruginosa acute pneumonia in mice
Marie-Sarah Fangous1,2, Philippe Gosset3, Nicolas Galakhoff2
1Laboratoire de biologie médicale, Centre Hospitalier de Cornouaille, Quimper, France.
Background:
Increasing resistance to antibiotics of Pseudomonas aeruginosa leads to therapeutic deadlock and alternative therapies are needed. We aimed to evaluate the effects of Lactobacillus clinical isolates in vivo, through intranasal administration on a murine model of Pseudomonas aeruginosa pneumonia.
Results:
We screened in vitro 50 pulmonary clinical isolates of Lactobacillus for their ability to decrease the synthesis of two QS dependent-virulence factors (elastase and pyocyanin) produced by Pseudomonas aeruginosa strain PAO1. Two blends of three Lactobacillus isolates were then tested in vivo: one with highly effective anti-PAO1 virulence factors properties (blend named L.rff for L. rhamnosus, two L. fermentum strains), and the second with no properties (blend named L.psb, for L. paracasei, L. salivarius and L. brevis). Each blend was administered intranasally to mice 18 h prior to PAO1 pulmonary infection. Animal survival, bacterial loads, cytological analysis, and cytokines secretion in the lungs were evaluated at 6 or 24 h post infection with PAO1. Intranasal priming with both lactobacilli blends significantly improved 7-day mice survival from 12% for the control PAO1 group to 71 and 100% for the two groups receiving L.rff and L.psb respectively. No mortality was observed for both control groups receiving either L.rff or L.psb. Additionally, the PAO1 lung clearance was significantly enhanced at 24 h. A 2-log and 4-log reduction was observed in the L.rff + PAO1 and L.psb + PAO1 groups respectively, compared to the control PAO1 group. Significant reductions in neutrophil recruitment and proinflammatory cytokine and chemokine secretion were observed after lactobacilli administration compared to saline solution, whereas IL-10 production was increased.
Conclusions:
These results demonstrate that intranasal priming with lactobacilli acts as a prophylaxis, and avoids fatal complications caused by Pseudomonas aeruginosa pneumonia in mice. These results were independent of in vitro anti-Pseudomonas aeruginosa activity on QS-dependent virulence factors. Further experiments are required to identify the immune mechanism before initiating clinical trials.
Insights
Intranasal administration of Lactobacillus isolates significantly improved survival in a mouse model of Pseudomonas aeruginosa pneumonia. This probiotic approach offers a promising alternative therapy for antibiotic-resistant bacterial infections.
Area of Science:
- Microbiology
- Immunology
- Probiotics
Background:
- Antibiotic resistance in Pseudomonas aeruginosa presents a significant therapeutic challenge.
- Alternative therapies are crucial for managing Pseudomonas aeruginosa infections.
Purpose of the Study:
- To evaluate the in vivo effects of Lactobacillus clinical isolates administered intranasally.
- To assess the efficacy of Lactobacillus in a murine model of Pseudomonas aeruginosa pneumonia.
Main Methods:
- Screening of 50 Lactobacillus isolates for in vitro anti-virulence factor activity.
- In vivo testing of two Lactobacillus blends (L.rff and L.psb) via intranasal administration in mice prior to Pseudomonas aeruginosa infection.
- Evaluation of survival rates, bacterial loads, lung cytology, and cytokine secretion.
Main Results:
- Both Lactobacillus blends significantly improved 7-day survival rates (71% and 100%) compared to the control group (12%).
- Intranasal Lactobacillus administration enhanced Pseudomonas aeruginosa lung clearance by 2-log and 4-log.
- Reduced neutrophil recruitment and pro-inflammatory cytokine secretion, with increased IL-10 production, were observed.
Conclusions:
- Intranasal Lactobacillus priming acts as a prophylaxis against fatal Pseudomonas aeruginosa pneumonia in mice.
- The protective effects were independent of in vitro anti-virulence factor activity.
- Further research into immune mechanisms is needed before clinical trials.
