Therapeutic potential of Bacillus phage lysin PlyB in ocular infections.

Therapeutic potential of Bacillus phage lysin PlyB in ocular infections.
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DOI:
10.1128/msphere.00044-23
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发表时间:
2023-08-24
期刊:
影响因子:
4.8
通讯作者:
--
中科院分区:
生物学2区
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--
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噬菌体裂解酶(即,噬菌体溶素)是通用抗生素对抗日益增长的抗微生物剂抗性的趋势替代物。革兰氏阳性蜡样芽孢杆菌引起最严重形式的眼内感染之一,通常导致完全视力丧失。它是一种固有的β-内酰胺酶耐药微生物,在眼睛中高度致炎,抗生素作为这些致盲感染的唯一治疗选择通常并不有益。噬菌体溶素作为治疗B的用途。蜡样眼感染从未被测试或报道。在这项研究中,噬菌体溶素Ply B在体外进行了测试,证明了快速杀死营养B。蜡状菌而不是其孢子。PlyB也是高度组特异性的,并且在各种细菌生长条件下有效地杀死细菌,包括离体兔玻璃体(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,也没有引发先天性激活。在体内治疗实验中,Ply B可有效杀死B。当在实验性眼内炎模型中玻璃体内给药和在实验性角膜炎模型中局部给药时,在两种眼部感染模型中,PlyB的有效杀菌特性可预防眼部组织的病理损伤。因此,发现Ply B可安全有效地杀死B。眼睛里的蜡状细胞,大大改善了原本毁灭性的结果。总体而言,本研究证明Ply B是B的一种有前景的治疗选择。蜡样眼病耐抗生素蜡样芽孢杆菌引起的眼部感染是毁灭性的,可能导致失明,而且可用的治疗方案很少。噬菌体溶素是传统抗生素的替代品,具有控制耐药性细菌的潜力。这项研究表明,一种名为Ply B的溶素可以有效地杀死B。两种B模型的蜡状核。蜡状菌眼部感染,从而治疗和预防这些感染的致盲作用。
Bacteriophage lytic enzymes (i.e., phage lysins) are a trending alternative for general antibiotics to combat growing antimicrobial resistance. Gram-positive Bacillus cereus 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 B. cereus ocular infection has never been tested or reported. In this study, the phage lysin PlyB was tested in vitro, demonstrating rapid killing of vegetative B. cereus but not its spores. PlyB was also highly group specific and effectively killed the bacteria in various bacterial growth conditions, including ex vivo rabbit vitreous (Vit). Furthermore, PlyB demonstrated no cytotoxic or hemolytic activity toward human retinal cells or erythrocytes and did not trigger innate activation. In in vivo therapeutic experiments, PlyB was effective in killing B. cereus 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 B. cereus in the eye, greatly improving an otherwise devastating outcome. Overall, this study demonstrates that PlyB is a promising therapeutic option for B. cereus eye infections. Eye infections from antibiotic-resistant Bacillus cereus 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 B. cereus in two models of B. cereus eye infections, thus treating and preventing the blinding effects of these infections.
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