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揭示螺旋藻藻提取物作为抗碳青霉烯类耐药肺炎克雷伯菌的有前景的抗菌和抗生物膜剂的潜力:体外和体内研究

Unveiling the potential of spirulina algal extract as promising antibacterial and antibiofilm agent against carbapenem-resistant Klebsiella pneumoniae: in vitro and in vivo study.

作者信息

Selim Mohamed I, El-Banna Tarek, Sonbol Fatma, Negm Walaa A, Elekhnawy Engy

机构信息

Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.

Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.

出版信息

Microb Cell Fact. 2025 Jan 5;24(1):7. doi: 10.1186/s12934-024-02619-3.

DOI:10.1186/s12934-024-02619-3
PMID:39755644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11700449/
Abstract

Carbapenem-resistant Klebsiella pneumoniae poses a severe risk to global public health, necessitating the immediate development of novel therapeutic strategies. The current study aimed to investigate the effectiveness of the green algae Arthrospira maxima (commercially known as Spirulina) both in vitro and in vivo against carbapenem-resistant K. pneumoniae. In this study, thirty carbapenem-resistant K. pneumoniae isolates were collected, identified, and then screened for their susceptibility to several antibiotics and carbapenemase production genes using PCR. Both bla and bla genes were the most predominant detected carbapenemase genes in the tested isolates. The phytochemical profiling of A. maxima algal extract was conducted using LC-MS/MS in a positive mode technique. The minimum inhibitory concentrations (MIC) of the algal extract ranged from 500 to 1000 µg/mL. The algal extract also resulted in decreasing the membrane integrity and distortion in the bacterial cells as revealed by scanning electron microscope. The bioactive compounds that were responsible for the antibacterial action were fatty acids, including PUFAs, polysaccharides, glycosides, peptides, flavonoids, phycocyanin, minerals, essential amino acids, and vitamins. Moreover, A. maxima algal extract revealed an antibiofilm activity by crystal violet assay and qRT-PCR. A murine pneumonia model was employed for the in vivo assessment of the antibacterial action of the algal extract. A. maxima showed a promising antibacterial action which was comparable to the action of colistin (standard drug). This was manifested by improving the pulmonary architecture, decreasing the inflammatory cell infiltration, and fibrosis after staining with hematoxylin and eosin and Masson's trichrome stain. Using immunohistochemical investigations, the percentage of the immunoreactive cells significantly decreased after using monoclonal antibodies of the tumor necrosis factor-alpha and interleukin six. So, A. maxima may be considered a new candidate for the development of new antibacterial medications.

摘要

耐碳青霉烯类肺炎克雷伯菌对全球公共卫生构成严重威胁,因此迫切需要立即开发新的治疗策略。当前研究旨在调查极大节旋藻(商业上称为螺旋藻)在体外和体内对耐碳青霉烯类肺炎克雷伯菌的有效性。在本研究中,收集并鉴定了30株耐碳青霉烯类肺炎克雷伯菌分离株,然后使用PCR筛选它们对几种抗生素的敏感性以及碳青霉烯酶产生基因。bla和bla基因是在所测试分离株中检测到的最主要的碳青霉烯酶基因。使用LC-MS/MS以正模式技术对极大节旋藻藻提取物进行植物化学分析。藻提取物的最低抑菌浓度(MIC)范围为500至1000μg/mL。扫描电子显微镜显示,藻提取物还导致细菌细胞膜完整性降低和细胞变形。负责抗菌作用的生物活性化合物包括脂肪酸(包括多不饱和脂肪酸)、多糖、糖苷、肽、黄酮类化合物、藻蓝蛋白、矿物质、必需氨基酸和维生素。此外,通过结晶紫测定和qRT-PCR,极大节旋藻藻提取物显示出抗生物膜活性。采用小鼠肺炎模型对藻提取物的抗菌作用进行体内评估。极大节旋藻显示出有前景的抗菌作用,与黏菌素(标准药物)的作用相当。这通过苏木精和伊红染色以及Masson三色染色后肺结构改善、炎症细胞浸润减少和纤维化得以体现。使用免疫组织化学研究,在用肿瘤坏死因子-α和白细胞介素6的单克隆抗体处理后,免疫反应性细胞的百分比显著降低。因此,极大节旋藻可被视为开发新型抗菌药物的新候选物。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b8d/11700449/52b1253578c0/12934_2024_2619_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b8d/11700449/628255d3941b/12934_2024_2619_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b8d/11700449/64175652031a/12934_2024_2619_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b8d/11700449/e727ca77c8e7/12934_2024_2619_Fig12_HTML.jpg

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