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杀菌性全人源单链可变片段抗体可保护小鼠免受耐甲氧西林菌血症的侵害。

Bactericidal fully human single-chain fragment variable antibodies protect mice against methicillin-resistant bacteraemia.

作者信息

Soltanmohammadi Behnoush, Piri-Gavgani Somayeh, Basardeh Eilnaz, Ghanei Mostafa, Azizi Masoumeh, Khaksar Zabihollah, Sharifzadeh Zahra, Badmasti Farzad, Soezi Mahdieh, Fateh Abolfazl, Azimi Parisa, Siadat Seyed Davar, Shooraj Fahimeh, Bouzari Saeid, Omrani Mir Davood, Rahimi-Jamnani Fatemeh

机构信息

Department of Mycobacteriology and Pulmonary Research Pasteur Institute of Iran Tehran Iran.

Microbiology Research Center Pasteur Institute of Iran Tehran Iran.

出版信息

Clin Transl Immunology. 2021 Jun 29;10(7):e1302. doi: 10.1002/cti2.1302. eCollection 2021.

DOI:10.1002/cti2.1302
PMID:34221401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8240403/
Abstract

OBJECTIVES: The increasing prevalence of antibiotic-resistant , besides the inadequate numbers of effective antibiotics, emphasises the need to find new therapeutic agents against this lethal pathogen. METHODS: In this study, to obtain antibody fragments against , a human single-chain fragment variable (scFv) library was enriched against living methicillin-resistant (MRSA) cells, grown in three different conditions, that is human peripheral blood mononuclear cells with plasma, whole blood and biofilm. The antibacterial activity of scFvs was evaluated by the growth inhibition assay . Furthermore, the therapeutic efficacy of anti-.  scFvs was appraised in a mouse model of bacteraemia. RESULTS: Three scFv antibodies, that is MEH63, MEH158 and MEH183, with unique sequences, were found, which exhibited significant binding to .  and reduced the viability of .  in inhibition assays. Based on the results, MEH63, MEH158 and MEH183, in addition to their combination, could prolong the survival rate, reduce the bacterial burden in the blood and prevent inflammation and tissue destruction in the kidneys and spleen of mice with MRSA bacteraemia compared with the vehicle group (treated with normal saline). CONCLUSION: The combination therapy with anti-.  scFvs and conventional antibiotics might shed light on the treatment of patients with infections.

摘要

目的：除有效抗生素数量不足外，抗生素耐药性的日益普遍凸显了寻找针对这种致命病原体的新治疗药物的必要性。 方法：在本研究中，为获得针对[病原体名称未给出]的抗体片段，利用在三种不同条件下生长的耐甲氧西林金黄色葡萄球菌（MRSA）细胞富集人单链可变片段（scFv）文库，这三种条件分别是人外周血单核细胞与血浆、全血和生物膜。通过生长抑制试验评估scFv的抗菌活性。此外，在菌血症小鼠模型中评估抗[病原体名称未给出]scFv的治疗效果。 结果：发现了三种具有独特序列的scFv抗体，即MEH63、MEH158和MEH183，它们与[病原体名称未给出]表现出显著结合，并在抑制试验中降低了[病原体名称未给出]的活力。基于这些结果，与载体组（用生理盐水处理）相比，MEH63、MEH158和MEH183及其组合可提高耐甲氧西林金黄色葡萄球菌菌血症小鼠的存活率，降低血液中的细菌载量，并预防肾脏和脾脏的炎症及组织破坏。 结论：抗[病原体名称未给出]scFv与传统抗生素的联合治疗可能为[病原体名称未给出]感染患者的治疗提供新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/1bc3df3d4fef/CTI2-10-e1302-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/fcc3c8cf2b54/CTI2-10-e1302-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/7dc2a924cb7f/CTI2-10-e1302-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/690294648889/CTI2-10-e1302-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/c1326c0125cc/CTI2-10-e1302-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/5fb079000710/CTI2-10-e1302-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/b3794b3895a2/CTI2-10-e1302-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/5bcf9c8d958e/CTI2-10-e1302-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/1bc3df3d4fef/CTI2-10-e1302-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/fcc3c8cf2b54/CTI2-10-e1302-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/7dc2a924cb7f/CTI2-10-e1302-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/690294648889/CTI2-10-e1302-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/c1326c0125cc/CTI2-10-e1302-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/5fb079000710/CTI2-10-e1302-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/b3794b3895a2/CTI2-10-e1302-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/5bcf9c8d958e/CTI2-10-e1302-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f939/8240403/1bc3df3d4fef/CTI2-10-e1302-g009.jpg

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[1]
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[2]
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J Immunol Res. 2024

[3]
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[4]
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[5]
Identification of two neutralizing human single-chain variable fragment antibodies targeting alpha-hemolysin.

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[6]
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BMC Biotechnol. 2022-10-28

[7]
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本文引用的文献

[1]
Synergistic Effect of Propidium Iodide and Small Molecule Antibiotics with the Antimicrobial Peptide Dendrimer G3KL against Gram-Negative Bacteria.

Molecules. 2020-11-30

[2]
The Role of ATP-Binding Cassette Transporters in Bacterial Phytopathogenesis.

Phytopathology. 2021-4

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Bee venom-derived antimicrobial peptide melectin has broad-spectrum potency, cell selectivity, and salt-resistant properties.

Sci Rep. 2020-6-23

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Targeting c-Met on gastric cancer cells through a fully human fab antibody isolated from a large naive phage antibody library.

Daru. 2020-6

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Antibody Binding to the O-Specific Antigen of Pseudomonas aeruginosa O6 Inhibits Cell Growth.

Antimicrob Agents Chemother. 2020-3-24

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Enantiomeric glycosylated cationic block co-beta-peptides eradicate Staphylococcus aureus biofilms and antibiotic-tolerant persisters.

Nat Commun. 2019-10-21

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Antibodies (Basel). 2018-1-4

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