Lactobacillus paracasei CFS boosts fibroblast `BCL2` expression 36-fold, mitigating *P. aeruginosa* cytotoxicity.
Background
The rise of antibiotic-resistant Pseudomonas aeruginosa poses a critical challenge in wound management, particularly in chronic and burn wounds, where conventional antibiotics often fail. This resistance leads to persistent infections and significant cytotoxicity to host cells like fibroblasts, impairing healing. There's an urgent need for alternative therapeutic strategies that can control infection while also protecting host tissue. Probiotic-derived products, such as cell-free supernatants (CFSs), offer a promising avenue by potentially combining antimicrobial effects with host cell protective properties, addressing this dual challenge.
Study Design
Researchers investigated four probiotic cell-free supernatants (CFSs) for their ability to control infections and mitigate cytotoxic effects on fibroblasts. They used antimicrobial broth microdilution assays against Staphylococcus aureus ATCC 25,923 and P. aeruginosa ATCC 27,853. GC-MS analysis, antioxidant activity, and hemolysis assays characterized the CFSs. The effects of probiotic CFSs, alone and in combination with P. aeruginosa CFS, were tested on human fibroblast cells (HFFs) using MTT assay for viability and qPCR for gene expression. The primary intervention focused on Lactobacillus paracasei CASEI431 CFS.
Results
Among the tested probiotic CFSs, Lactobacillus paracasei CASEI431 demonstrated antimicrobial activity against S. aureus and P. aeruginosa, with a minimum inhibitory concentration (MIC) of 6.25 mg/mL. While Bifidobacterium animalis CFS showed the strongest toxicity to fibroblast cells, L. paracasei CFS had the most positive effect on fibroblast proliferation. Treatment of HFFs with pathogenic P. aeruginosa CFS significantly reduced cell viability. Although co-treatment with L. paracasei CFS did not significantly increase cell viability as measured by MTT assay, it profoundly impacted gene expression.
Co-treatment with
L. paracaseiCFS caused a significant upregulation of the anti-apoptotic geneBCL2by approximately 3-fold after 24 hours and a remarkable 36-fold after 72 hours, compared to pathogenic CFS treatment alone.
Key Findings
- Lactobacillus paracasei CASEI431 CFS exhibited antimicrobial activity against P. aeruginosa with an MIC of 6.25 mg/mL.
- Lactobacillus paracasei CFS positively affected fibroblast proliferation, while Bifidobacterium animalis CFS showed toxicity.
- Pathogenic P. aeruginosa CFS significantly reduced human fibroblast (HFF) viability.
- Co-treatment with Lactobacillus paracasei CFS significantly upregulated the anti-apoptotic gene
BCL2by ~3-fold at 24h. - Co-treatment with Lactobacillus paracasei CFS significantly upregulated
BCL2by ~36-fold at 72h compared to pathogenic CFS alone.
Why It Matters
This study highlights that probiotic-derived products, specifically Lactobacillus paracasei CFS, could serve as a complementary therapy for accelerating chronic wound healing, particularly in the context of antibiotic-resistant infections. The ability to not only control pathogens but also protect host cells by upregulating anti-apoptotic genes like BCL2 offers a novel therapeutic angle beyond traditional antibiotics. While promising, this is a preclinical in vitro finding, meaning it's far from a usable clinical protocol. Future research needs to validate these effects in in vivo models and fully elucidate the underlying signaling pathways before any translation to human use or specific dosing recommendations can be considered.
lactobacillus-paracasei
probiotic
wound-healing
pseudomonas-aeruginosa
antibiotic-resistance
fibroblast