Abstract

Pneumococcal infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality globally, particularly among children. The ability of S. pneumoniae to form enduring biofilms makes treatment inherently difficult, and options are further limited by emerging antibiotic resistance. The discovery of new antibiotics, particularly those with antibiofilm activity, is therefore increasingly important. Antimicrobial proteins and peptides (AMPs) from marine invertebrates are recognised as promising pharmacological leads. This study determined the in vitro antibacterial activity of hemolymph and unique protein fractions from an Australian oyster (Saccostrea glomerata) against multi-drug-resistant S. pneumoniae. We developed a successful method for hemolymph extraction and separation into 16 fractions by preparative HPLC. The strongest activity was observed in fraction 7: at 42 µg/mL protein, this fraction was bactericidal to S. pneumoniae and inhibited biofilm formation. Proteomic analysis showed that fraction 7 contained relatively high abundance of carbonic anhydrase, cofilin, cystatin B–like, and gelsolin-like proteins, while surrounding fractions, which showed lower or no antibacterial activity, contained these proteins in lower abundance or not at all. This work supports traditional medicinal uses of oysters and contributes to further research and development of novel hemolymph/AMP-based treatments for pneumococcal infections.

中文翻译：

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来自牡蛎血淋巴的半纯化抗菌蛋白可抑制肺炎球菌感染

摘要

由肺炎链球菌引起的肺炎球菌感染是全球尤其是儿童发病和死亡的主要原因。肺炎链球菌形成持久生物膜的能力使得治疗本身就很困难，而且新出现的抗生素耐药性进一步限制了治疗选择。因此，新抗生素的发现，特别是具有抗生物膜活性的抗生素，变得越来越重要。来自海洋无脊椎动物的抗菌蛋白和肽 (AMP) 被认为是有前途的药理学先导化合物。本研究确定了澳大利亚牡蛎（Saccostrea glomerata）血淋巴和独特蛋白质组分对多重耐药肺炎链球菌的体外抗菌活性。我们开发了一种成功的方法，通过制备型 HPLC 提取血淋巴并分离成 16 个组分。在组分 7 中观察到最强的活性：在 42 µg/mL 蛋白质下，该组分对肺炎链球菌具有杀菌作用并抑制生物膜形成。蛋白质组学分析表明，级分 7 含有相对较高丰度的碳酸酐酶、肌动蛋白丝切蛋白、半胱氨酸蛋白酶抑制剂 B 样和凝溶胶蛋白样蛋白质，而周围的级分显示​​出较低的抗菌活性或没有抗菌活性，则含有丰度较低或根本不含这些蛋白质。这项工作支持牡蛎的传统医学用途，并有助于进一步研究和开发基于血淋巴/AMP 的新型肺炎球菌感染治疗方法。