Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Dean McGee Eye Institute, Oklahoma City, Oklahoma, USA.
mSphere. 2023 Aug 24;8(4):e0004423. doi: 10.1128/msphere.00044-23. Epub 2023 Jun 5.
Bacteriophage lytic enzymes (i.e., phage lysins) are a trending alternative for general antibiotics to combat growing antimicrobial resistance. Gram-positive causes one of the most severe forms of intraocular infection, often resulting in complete vision loss. It is an inherently β-lactamase-resistant organism that is highly inflammogenic in the eye, and antibiotics are not often beneficial as the sole therapeutic option for these blinding infections. The use of phage lysins as a treatment for ocular infection has never been tested or reported. In this study, the phage lysin PlyB was tested , demonstrating rapid killing of vegetative but not its spores. PlyB was also highly group specific and effectively killed the bacteria in various bacterial growth conditions, including rabbit vitreous (Vit). Furthermore, PlyB demonstrated no cytotoxic or hemolytic activity toward human retinal cells or erythrocytes and did not trigger innate activation. In therapeutic experiments, PlyB was effective in killing when administered intravitreally in an experimental endophthalmitis model and topically in an experimental keratitis model. In both models of ocular infection, the effective bactericidal property of PlyB prevented pathological damage to ocular tissues. Thus, PlyB was found to be safe and effective in killing in the eye, greatly improving an otherwise devastating outcome. Overall, this study demonstrates that PlyB is a promising therapeutic option for eye infections.IMPORTANCEEye infections from antibiotic-resistant are devastating and can result in blindness with few available treatment options. Bacteriophage lysins are an alternative to conventional antibiotics with the potential to control antibiotic-resistant bacteria. This study demonstrates that a lysin called PlyB can effectively kill in two models of eye infections, thus treating and preventing the blinding effects of these infections.
噬菌体裂解酶（即噬菌体溶素）是一种有前途的抗生素替代品，可用于对抗日益严重的抗微生物药物耐药性。革兰氏阳性菌是引起最严重的眼内感染形式之一的原因，通常导致完全失明。它是一种固有耐β-内酰胺酶的生物体，在眼睛中高度致炎，抗生素通常不是这些致盲感染的唯一治疗选择。噬菌体溶素作为治疗 眼部感染的用途从未经过测试或报道。在这项研究中，测试了噬菌体溶素 PlyB，证明它可以快速杀死营养型 ，但不能杀死其孢子。 PlyB 也具有高度的群体特异性，能够有效地杀死各种细菌生长条件下的细菌，包括兔玻璃体（Vit）。此外， PlyB 对人视网膜细胞或红细胞没有细胞毒性或溶血活性，也不会引发先天激活。在治疗实验中，PlyB 在实验性眼内炎模型中玻璃体内给药和实验性角膜炎模型中局部给药时对 有效，可杀死 。在这两种眼部感染模型中，PlyB 的有效杀菌特性可防止眼组织发生病理损伤。因此，PlyB 被发现可安全有效地杀死眼内的 ，极大地改善了否则会导致毁灭性后果的疾病。总体而言，这项研究表明 PlyB 是治疗 眼部感染的有前途的治疗选择。
