Therapeutic effect of polyclonal lipoprotein SA2275 antibodies on <italic style="font-style: italic">Staphylococcus aureus</italic>-induced brain abscess in mice

Ying ZHENG; Yi YANG; Huagang PENG; Yifan RAO; Zhen HU; Qiwen HU; Lianmei ZHONG; Xiancai RAO; Weilong SHANG; Renjie ZHOU

doi:10.16016/j.1000-5404.202002210

您当前的位置：

首页 >

文章列表页 >

Therapeutic effect of polyclonal lipoprotein SA2275 antibodies on Staphylococcus aureus-induced brain abscess in mice

Basic Medicine | 更新时间：2026-01-09

- Therapeutic effect of polyclonal lipoprotein SA2275 antibodies on Staphylococcus aureus-induced brain abscess in mice
- Journal of Third Military Medical University Vol. 42, Issue 16, Pages: 1655-1662(2020)
- 作者机构：
  
  1.650032 昆明，昆明医科大学第一附属医院神经内科
  2.400038 重庆，陆军军医大学(第三军医大学)基础医学院微生物学教研室，重庆市微生物工程实验室
  3.400715 重庆，西南大学生命科学学院, 现代生物医药研究所, 三峡库区生态环境与生物资源省部共建国家重点实验室培育基地
  4.400037 重庆，陆军军医大学(第三军医大学)第二附属医院急诊部
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81701967)
- DOI：10.16016/j.1000-5404.202002210
  CLC： R378.11;R742.7;R977.6
- Received：27 February 2020，
  
  Revised：2020-05-27，
  
  Published：30 August 2020
- 稿件说明：
移动端阅览
Ying ZHENG, Yi YANG, Huagang PENG, et al. Therapeutic effect of polyclonal lipoprotein SA2275 antibodies on Staphylococcus aureus-induced brain abscess in mice[J]. Journal of Third Military Medical University, 2020, 42(16): 1655-1662.
DOI：

Ying ZHENG, Yi YANG, Huagang PENG, et al. Therapeutic effect of polyclonal lipoprotein SA2275 antibodies on Staphylococcus aureus-induced brain abscess in mice[J]. Journal of Third Military Medical University, 2020, 42(16): 1655-1662. DOI： 10.16016/j.1000-5404.202002210.

摘要

目的

探讨脂蛋白特异性抗体通过血脑屏障及其在抑制金黄色葡萄球菌脑脓肿形成中的作用。

方法

利用大肠埃希菌表达并纯化重组金葡菌脂蛋白SA2275，制备特异性小鼠多克隆抗体(anti-SA2275)。制作金葡菌感染脑脓肿模型，利用ELISA法检测经腹腔注射的anti-SA2275在小鼠脑组织中的滴度，评估抗体通过血脑屏障的能力；再利用梯度稀释细菌计数法检测脑脓肿中的细菌载量，对脑脓肿进行连续病理切片检测脑脓肿的大小，评价抗体anti-SA2275治疗金葡菌脑脓肿的效果。

结果

成功获得高纯度SA2275重组蛋白；免疫小鼠获得anti-SA2275，效价为1:51 200；anti-SA2275注射金葡菌脑脓肿模型小鼠后，在动物脑组织中检测到抗体的存在；治疗组小鼠脑脓肿大小和菌载量显著低于阴性对照组。

结论

在金葡菌感染小鼠所致的脑脓肿形成过程中，脂蛋白SA2275特异性抗体可以通过血脑屏障分布至脑组织，显著抑制脑脓肿的形成及细菌的定植，具有治疗金葡菌脑脓肿的应用前景。

Abstract

Objective

To investigate the ability of specific polyclonal antibodies against

Staphylococcus aureus

(

S. aureus

) lipoprotein SA2275 to penetrate the blood-brain barrier for inhibiting the formation of

S. aureus

-induced brain abscess in mice.

Methods

We immunized BALB/c mouse mice with purified recombinant

S. aureus

lipoprotein SA2275 expressed in

Escherichia coli

to obtain specific mouse polyclonal antibodies against SA2275 (anti-SA2275). In a C57BL/6 mouse model of brain abscess induced by injecting

S. aureus

strain Newman into the brain

we tested the titer of anti-SA2275 in the brain tissue using ELISA following intraperitoneal injection of the antibodies to evaluate the ability of the antibodies to pass through the blood-brain barrier. The bacterial load in the mouse brain was determined by gradient dilution bacterial counting

and the size of the brain abscess was evaluated on serial sections.

Results

The recombinant SA2275 protein with a high purity was successfully obtained. The results of ELISA showed that immunization of the mice with the recombinant SA2275 protein resulted in a high titer of anti-SA2275 reaching 1:51 200. In the mouse models of

S. aureus

-induced brain abscess

the presence of the antibodies was detected in the brain tissue after intraperitoneal injection of anti-SA2275. Treatment with anti-SA2275

as compared with blank control mouse serum

significantly reduced the size of the brain abscess and lowered the bacterial load in the brain tissues of the mice.

Conclusion

In mouse models of

S. aureus

-induced brain abscess

intraperitoneally injected lipoprotein SA2275-specific antibodies can penetrate the blood-brain barrier to reach the brain tissue and inhibit the formation of brain abscess and bacterial colonization

suggesting the potential of the antibodies for treatment of

S. aureus

-induced brain abscess.

关键词

Keywords

references

BROUWER M C, COUTINHO J M, VAN DE BEEK D. Clinical characteristics and outcome of brain abscess: systematic review and meta-analysis[J]. Neurology, 2014, 82(9): 806-813. DOI: 10.1212/WNL.0000000000000172.

PATEL K, CLIFFORD D B. Bacterial brain abscess[J]. Neurohospitalist, 2014, 4(4): 196-204. DOI: 10.1177/1941874414540684.

BROUWER M C, TUNKEL A R, MCKHANN G M Ⅱ, et al . Brain abscess[J ] . N Engl J Med, 2014, 371(5): 447-456. DOI: 10.1056/nejmra1301635.

WOODHOUSE A. Bacterial meningitis and brain abscess[J]. Medicine, 2017, 45(11): 657-663. DOI: 10.1016/j.mpmed.2017.08.012.

MVHLEN S, DERSCH P. Anti-virulence strategies to target bacterial infections[J]. Curr Top Microbiol Immunol, 2016, 398: 147-183. DOI: 10.1007/82_2015_490.

BALDWIN A C, KIELIAN T. Persistent immune activation associated with a mouse model of Staphylococcus aureus-induced experimental brain abscess[J ] . J Neuroimmunol, 2004, 151(1/2): 24-32. DOI: 10.1016/j.jneuroim.2004.02.002.

ZHENG Y, SHANG W L, PENG H G, et al . Virulence determinants are required for brain abscess formation through Staphylococcus aureus infection and are potential targets of antivirulence factor therapy[J ] . Front Microbiol, 2019, 10: 682. DOI: 10.3389/fmicb.2019.00682..

SHANG W L, RAO Y F, ZHENG Y, et al . B-lactam antibiotics enhance the pathogenicity of methicillin-resistant Staphylococcus aureus via SarA-controll ed lipoprotein-like cluster expression[J ] . mBio, 2019, 10(3): e00880-e00819. DOI: 10.1128/mBio.00880-19..

BLOCH O, PAPADOPOULOS M C, MANLEY G T, et al . Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess[J ] . J Neurochem, 2005, 95(1): 254-262. DOI: 10.1111/j.1471-4159.2005.03362.x.

TACCONELLI E, CARRARA E, SAVOLDI A, et al . Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis[J ] . Lancet Infect Dis, 2018, 18(3): 318-327. DOI: 10.1016/S1473-3099(17)30753-3.

GUARNER F, MALAGELADA J R. Gut flora in health and disease[J]. Lancet, 2003, 361(9356): 512-519. DOI: 10.1016/s0140-6736(03)12489-0.

SAYLOR C, DADACHOVA E, CASADEVALL A. Monoclonal antibody-based therapies for microbial diseases[J]. Vaccine, 2009, 27(Suppl 6): G38-G46. DOI: 10.1016/j.vaccine.2009.09.105.

CHOW S K, CASADEVALL A. Monoclonal antibodies and toxins: a perspective on function and isotype[J]. Toxins (Basel), 2012, 4(6): 430-454. DOI: 10.3390/toxins4060430.

PARDRIDGE W M. Biopharmaceutical drug targeting to the brain[J]. J Drug Target, 2010, 18(3): 157-167. DOI: 10.3109/10611860903548354.

AZAD T D, PAN J, CONNOLLY I D, et al . Therapeutic strategies to improve drug delivery across the blood-brain barrier[J ] . Neurosurg Focus, 2015, 38(3): E9. DOI: 10.3171/2014.12.FOCUS14758.

FLESSNER M F, DEDRICK R L. Tissue-level transport mechanisms of intraperitoneally-administered monoclonal antibodies[J]. J Control Release, 1998, 53(1/2/3): 69-75. DOI: 10.1016/s0168-3659(97)00238-1.

MCLOUGHLIN A, ROCHFORT K D, MCDONNELL C J, et al . Staphylococcus aureus -mediated blood-brain barrier injury: an in vitro human brain microvascular endothelial cell model[J ] . Cell Microbiol, 2017, 19(3). DOI: 10.1111/cmi.12664..

NGUYEN M T, GÖTZ F. Lipoproteins of gram-positive bacteria: key players in the immune response and virulence[J]. Microbiol Mol Biol Rev, 2016, 80(3): 891-903. DOI: 10.1128/MMBR.00028-16.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Experimental Research on β-toxin of Staphylococcus aureus promotes breaking the blood-brain barrier in mice

Recombinant annexin A2 improves early neurological function through blood-brain barrier protection in mice after controlled cortical impact

WalK(S221P) mutation promotes production of Staphylococcus aureus capsule

Construction of Staphylococcus aureus bioluminescence tracing system based on Antares2

Related Author

王哲芬

尹靓

陈韬

吴静琳

郑颖

Weina CHAI

Chongjie CHENG

Li JIANG

Related Institution

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University

Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University)

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burns, Army Medical University (Third Military Medical University)

Department of Orthopedics, Center of Plastic Surgery, First Affiliated Hospital, Army Medical University (Third Military Medical University)

⁰

Therapeutic effect of polyclonal lipoprotein SA2275 antibodies on Staphylococcus aureus-induced brain abscess in mice

DOI：10.16016/j.1000-5404.202002210

摘要

Abstract

关键词

Keywords

references