The Charles T. Campbell Laboratory, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ocul Surf. 2023 Apr;28:254-261. doi: 10.1016/j.jtos.2023.05.002. Epub 2023 May 3.
Pseudomonas aeruginosa keratitis is a severe ocular infection that can lead to perforation of the cornea. In this study we evaluated the role of bacterial quorum sensing in generating corneal perforation and bacterial proliferation and tested whether co-injection of the predatory bacteria Bdellovibrio bacteriovorus could alter the clinical outcome. P. aeruginosa with lasR mutations were observed among keratitis isolates from a study collecting samples from India, so an isogenic lasR mutant strain of P. aeruginosa was included.
Rabbit corneas were intracorneally infected with P. aeruginosa strain PA14 or an isogenic ΔlasR mutant and co-injected with PBS or B. bacteriovorus. After 24 h, eyes were evaluated for clinical signs of infection. Samples were analyzed by scanning electron microscopy, optical coherence tomography, sectioned for histology, and corneas were homogenized for CFU enumeration and for inflammatory cytokines.
We observed that 54% of corneas infected by wild-type PA14 presented with a corneal perforation (n = 24), whereas only 4% of PA14 infected corneas that were co-infected with B. bacteriovorus perforate (n = 25). Wild-type P. aeruginosa proliferation was reduced 7-fold in the predatory bacteria treated eyes. The ΔlasR mutant was less able to proliferate compared to the wild-type, but was largely unaffected by B. bacteriovorus.
These studies indicate a role for bacterial quorum sensing in the ability of P. aeruginosa to proliferate and cause perforation of the rabbit cornea. Additionally, this study suggests that predatory bacteria can reduce the virulence of P. aeruginosa in an ocular prophylaxis model.
铜绿假单胞菌角膜炎是一种严重的眼部感染，可导致角膜穿孔。在这项研究中，我们评估了细菌群体感应在产生角膜穿孔和细菌增殖中的作用，并测试了捕食性细菌蛭弧菌共注射是否可以改变临床结果。在一项从印度收集样本的研究中，从角膜炎分离物中观察到 lasR 突变的铜绿假单胞菌，因此包括了铜绿假单胞菌的同源 lasR 突变株。
用铜绿假单胞菌 PA14 或同源ΔlasR 突变株经角膜内感染兔角膜，并与 PBS 或 B. bacteriovorus 共注射。24 小时后，评估眼睛感染的临床症状。通过扫描电子显微镜、光学相干断层扫描、组织学切片、CFU 计数和炎症细胞因子对样本进行分析。
我们观察到，54%的野生型 PA14 感染角膜出现角膜穿孔（n=24），而只有 4%的与 B. bacteriovorus 共感染的 PA14 感染角膜穿孔（n=25）。在捕食性细菌处理的眼中，野生型铜绿假单胞菌的增殖减少了 7 倍。与野生型相比，ΔlasR 突变体的增殖能力降低，但受 B. bacteriovorus 的影响不大。
这些研究表明，细菌群体感应在铜绿假单胞菌增殖和导致兔角膜穿孔的能力中起作用。此外，这项研究表明，捕食性细菌可以降低铜绿假单胞菌在眼部预防模型中的毒力。
