Mesh : Pseudomonas aeruginosa / metabolism pathogenicity Glucose / metabolism Animals Type III Secretion Systems / metabolism genetics Propionibacterium acnes / growth & development physiology metabolism Wound Infection / microbiology Mice Pseudomonas Infections / microbiology Skin / microbiology Carbon / metabolism Wound Healing Antibiosis Disease Progression Humans

来  源:   DOI:10.1038/s41522-024-00518-4   PDF(Pubmed)

Abstract:
It is becoming increasingly apparent that commensal skin bacteria have an important role in wound healing and infection progression. However, the precise mechanisms underpinning many of these probiotic interactions remain to be fully uncovered. In this work, we demonstrate that the common skin commensal Cutibacterium acnes can limit the pathogenicity of the prevalent wound pathogen Pseudomonas aeruginosa in vivo. We show that this impact on pathogenicity is independent of any effect on growth, but occurs through a significant downregulation of the Type Three Secretion System (T3SS), the primary toxin secretion system utilised by P. aeruginosa in eukaryotic infection. We also show a downregulation in glucose acquisition systems, a known regulator of the T3SS, suggesting that glucose availability in a wound can influence infection progression. C. acnes is well known as a glucose fermenting organism, and we demonstrate that topically supplementing a wound with glucose reverses the probiotic effects of C. acnes. This suggests that introducing carbon source competition within the wound microenvironment may be an effective way to prevent or limit wound infection.
摘要:
越来越明显的是共生皮肤细菌在伤口愈合和感染进展中具有重要作用。然而,支持许多益生菌相互作用的确切机制仍有待完全揭示。在这项工作中,我们证明,常见的皮肤共生痤疮杆菌可以限制流行的伤口病原体铜绿假单胞菌在体内的致病性。我们表明,这种对致病性的影响与对生长的任何影响无关,但通过三型分泌系统(T3SS)的显著下调而发生,铜绿假单胞菌在真核感染中利用的主要毒素分泌系统。我们还显示了葡萄糖采集系统的下调,已知的T3SS调节器,这表明伤口中葡萄糖的可用性可以影响感染进展。痤疮杆菌是众所周知的葡萄糖发酵生物,我们证明局部补充葡萄糖可以逆转痤疮杆菌的益生菌作用。这表明在伤口微环境中引入碳源竞争可能是预防或限制伤口感染的有效方法。
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