Romanowski Eric G, Stella Nicholas A, Brazile Bryn L, Lathrop Kira L, Franks Jonathan, Sigal Ian A, Kim Tami, Elsayed Mennat, Kadouri Daniel E, Shanks Robert M Q
The Charles T. Campbell Laboratory, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
bioRxiv. 2023 Mar 15:2023.03.15.532777. doi: 10.1101/2023.03.15.532777.
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 could alter the clinical outcome. with mutations were observed among keratitis isolates from a study collecting samples from India, so an isogenic mutant strain of was included.
Rabbit corneas were intracorneally infected with strain PA14 or an isogenic Δ mutant and co-injected with PBS or . 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 perforate (n=25). Wild-type proliferation was reduced 7-fold in the predatory bacteria treated eyes. The Δ mutant was less able to proliferate compared to the wild-type, but was largely unaffected by .
These studies indicate a role for bacterial quorum sensing in the ability of to proliferate and cause perforation of the rabbit cornea. Additionally, this study suggests that predatory bacteria can reduce the virulence of in an ocular prophylaxis model.
角膜炎是一种严重的眼部感染，可导致角膜穿孔。在本研究中，我们评估了细菌群体感应在导致角膜穿孔和细菌增殖中的作用，并测试了共注射捕食性细菌是否会改变临床结果。在一项从印度收集样本的研究中，角膜炎分离株中观察到有突变，因此纳入了一个等基因的突变菌株。
兔角膜经角膜内感染PA14菌株或等基因的Δ突变体，并与磷酸盐缓冲液（PBS）或[具体物质未给出]共注射。24小时后，评估眼睛的感染临床体征。通过扫描电子显微镜、光学相干断层扫描对样本进行分析，切片进行组织学检查，并将角膜匀浆用于菌落形成单位（CFU）计数和炎性细胞因子检测。
我们观察到，野生型PA14感染的角膜中有54%出现角膜穿孔（n = 24），而在与[具体物质未给出]共同感染的PA14感染角膜中，只有4%发生穿孔（n = 25）。在经捕食性细菌处理的眼中，野生型[具体菌名未给出]的增殖减少了7倍。与野生型相比，Δ突变体的增殖能力较弱，但在很大程度上不受[具体物质未给出]的影响。
这些研究表明细菌群体感应在[具体菌名未给出]增殖和导致兔角膜穿孔的能力中发挥作用。此外，本研究表明在眼部预防模型中，捕食性细菌可降低[具体菌名未给出]的毒力。
