State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Appl Environ Microbiol. 2024 Aug 21;90(8):e0046124. doi: 10.1128/aem.00461-24. Epub 2024 Jul 16.
() is an important opportunistic zoonotic pathogen that poses a potential threat to the animal husbandry industry, such as cow mastitis, due to the widespread development of multidrug-resistant strains. Phage lysins have emerged as a promising alternative antibiotic treatment strategy. However, no lysins have been reported to treat infections. In this study, the critical active domain and key active sites of the first phage lysin AVPL were revealed. AVPL consists of an N-terminal N-acetylmuramoyl-L-alanine amidase catalytic domain and a C-terminal binding domain comprising two conserved LysM. H40, N44, E52, W68, H147, T157, F60, F64, I77, N92, Q97, H159, V160, D161, and S42 were identified as key sites for maintaining the activity of the catalytic domain. The LysM motif plays a crucial role in binding AVPL to bacterial cell wall peptidoglycan. AVPL maintains stable activity in the temperature range of 4-45°C and pH range of 4-10, and its activity is independent of the presence of metal ions. the bactericidal effect of AVPL showed efficient bactericidal activity in milk samples, with 2 µg/mL of AVPL reducing by approximately 2 Log in 1 h. Furthermore, a single dose (25 µg) of lysin AVPL significantly reduces bacterial load (approximately 2 Log in the mammary gland of mice, improves mastitis pathology, and reduces the concentration of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in mammary tissue. Overall, this work provides a novel alternative therapeutic drug for mastitis induced by multidrug-resistant .
is a zoonotic pathogen known to cause various diseases, including mastitis in dairy cows. In recent years, there has been an increase in antibiotic-resistant or multidrug-resistant strains of this pathogen. Phage lysins are an effective approach to treating infections caused by multidrug-resistant strains. This study revealed the biological properties and key active sites of the first phage lysin named AVPL. AVPL can effectively kill multidrug-resistant in pasteurized whole milk. Importantly, 25 μg AVPL significantly alleviates the symptoms of mouse mastitis induced by . Overall, our results demonstrate the potential of lysin AVPL as an antimicrobial agent for the treatment of mastitis caused by .
（）是一种重要的机会性人畜共患病病原体，由于多药耐药菌株的广泛发展，对畜牧业构成了潜在威胁，如奶牛乳腺炎。噬菌体裂解酶作为一种有前途的抗生素替代治疗策略而出现。然而，尚无裂解酶用于治疗 感染的报道。在本研究中，揭示了第一个 噬菌体裂解酶 AVPL 的关键活性结构域和关键活性位点。AVPL 由一个 N-末端 N-乙酰基胞壁酰-L-丙氨酸酰胺酶催化结构域和一个包含两个保守 LysM 的 C-末端结合结构域组成。H40、N44、E52、W68、H147、T157、F60、F64、I77、N92、Q97、H159、V160、D161 和 S42 被鉴定为维持催化结构域活性的关键位点。LysM 基序在 AVPL 与细菌细胞壁肽聚糖的结合中起关键作用。AVPL 在 4-45°C 的温度范围和 4-10 的 pH 范围内保持稳定的活性，其活性不依赖于金属离子的存在。AVPL 的杀菌作用在牛奶样品中表现出有效的杀菌活性，2 µg/mL 的 AVPL 在 1 小时内使 减少约 2 Log。此外，单次剂量（25 µg）的裂解酶 AVPL 可显著降低小鼠乳腺中的细菌负荷（约 2 Log），改善乳腺炎病理，并降低乳腺组织中炎症细胞因子（TNF-α、IL-1β 和 IL-6）的浓度。总体而言，这项工作为多药耐药 引起的乳腺炎提供了一种新的治疗选择。
是一种已知会引起各种疾病的人畜共患病病原体，包括奶牛乳腺炎。近年来，这种病原体的抗生素耐药或多药耐药菌株有所增加。噬菌体裂解酶是治疗多药耐药菌株引起的感染的有效方法。本研究揭示了第一个名为 AVPL 的 噬菌体裂解酶的生物学特性和关键活性位点。AVPL 可有效杀灭多药耐药 株在巴氏杀菌全脂牛奶中的生长。重要的是，25 μg AVPL 可显著缓解 诱导的小鼠乳腺炎的症状。总体而言，我们的研究结果表明裂解酶 AVPL 作为一种治疗多药耐药 引起的乳腺炎的抗菌剂具有潜在的应用前景。
