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人类抗体库中经常包含针对一种与细菌生物膜相关的蛋白质的抗体。

Human antibody repertoire frequently includes antibodies to a bacterial biofilm associated protein.

机构信息

Trellis Bioscience LLC, Redwood City, California, United States of America.

出版信息

PLoS One. 2019 Jul 9;14(7):e0219256. doi: 10.1371/journal.pone.0219256. eCollection 2019.

Abstract

We have previously described a native human monoclonal antibody, TRL1068, that disrupts bacterial biofilms by extracting from the biofilm matrix key scaffolding proteins in the DNABII family, which are present in both gram positive and gram negative bacterial species. The antibiotic resistant sessile bacteria released from the biofilm then revert to the antibiotic sensitive planktonic state. Qualitative resensitization to antibiotics has been demonstrated in three rodent models of acute infections. We report here the surprising discovery that antibodies against the target family were found in all twenty healthy humans surveyed, albeit at a low level requiring a sensitive single B-cell assay for detection. We have cloned 21 such antibodies. Aside from TRL1068, only one (TRL1330) has all the biochemical properties believed necessary for pharmacological efficacy (broad spectrum epitope specificity and high affinity). We suggest that the other anti-DNABII antibodies, while not necessarily curative, reflect an immune response at some point in the donor's history to these components of biofilms. Such an immune response could reflect exposure to bacterial reservoirs that have been previously described in chronic non-healing wounds, periodontal disease, chronic obstructive pulmonary disease, colorectal cancer, rheumatoid arthritis, and atherosclerotic artery explants. The detection of anti-DNABII antibodies in all twenty surveyed donors with no active infection suggests that bacterial biofilm reservoirs may be present periodically in most healthy individuals. Biofilms routinely shed bacteria, creating a continuous low level inflammatory stimulus. Since chronic subclinical inflammation is thought to contribute to most aging-related diseases, suppression of bacterial biofilm has potential value in delaying age-related pathology.

摘要

我们之前描述了一种天然的人源单克隆抗体 TRL1068,它通过从生物膜基质中提取 DNAII 家族中的关键支架蛋白来破坏细菌生物膜,这些蛋白存在于革兰氏阳性和革兰氏阴性细菌物种中。从生物膜中释放的抗生素耐药性固着细菌随后恢复为抗生素敏感的浮游状态。在三种急性感染的啮齿动物模型中已经证明了定性再敏化。我们在这里报告了一个令人惊讶的发现,即在所有 20 名接受调查的健康人中都发现了针对靶家族的抗体,尽管水平较低,需要进行敏感的单细胞检测才能检测到。我们已经克隆了 21 种这样的抗体。除了 TRL1068 之外,只有一种(TRL1330)具有被认为对药理疗效至关重要的所有生化特性(广谱表位特异性和高亲和力)。我们认为,其他抗 DNAII 抗体虽然不一定具有治疗作用,但反映了供体历史上某个时间点对生物膜这些成分的免疫反应。这种免疫反应可能反映了对先前在慢性非愈合性伤口、牙周病、慢性阻塞性肺疾病、结直肠癌、类风湿性关节炎和动脉粥样硬化动脉外植体中描述的细菌储库的暴露。在所有 20 名接受调查的无活动性感染供体中都检测到抗 DNAII 抗体表明,细菌生物膜储库可能在大多数健康个体中定期存在。生物膜经常脱落细菌,产生持续的低水平炎症刺激。由于慢性亚临床炎症被认为是大多数与衰老相关疾病的原因,因此抑制细菌生物膜具有延迟与衰老相关的病理学的潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fac/6615618/d5437cd7c212/pone.0219256.g001.jpg

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