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Aggregatibacter actinomycetemcomitans leukotoxin: From mechanism to targeted anti-toxin therapeutics.
Molecular Oral Microbiology ( IF 2.8 ) Pub Date : 2020-03-10 , DOI: 10.1111/omi.12284
Eric Krueger 1 , Angela C Brown 1
Affiliation  

Aggregatibacter actinomycetemcomitans is a Gram‐negative bacterium associated with localized aggressive periodontitis, as well as other systemic diseases. This organism produces a number of virulence factors, all of which provide some advantage to the bacterium. Several studies have demonstrated that clinical isolates from diseased patients, particularly those of African descent, frequently belong to specific clones of A. actinomycetemcomitans that produce significantly higher amounts of a protein exotoxin belonging to the repeats‐in‐toxin (RTX) family, leukotoxin (LtxA), whereas isolates from healthy patients harbor minimally leukotoxic strains. This finding suggests that LtxA might play a key role in A. actinomycetemcomitans pathogenicity. Because of this correlation, much work over the past 30 years has been focused on understanding the mechanisms by which LtxA interacts with and kills host cells. In this article, we review those findings, highlight the remaining open questions, and demonstrate how knowledge of these mechanisms, particularly the toxin's interactions with lymphocyte function‐associated antigen‐1 (LFA‐1) and cholesterol, enables the design of targeted anti‐LtxA strategies to prevent/treat disease.

中文翻译:


放线菌白细胞毒素聚集菌:从机制到靶向抗毒素治疗。



放线菌聚集菌是一种与局部侵袭性牙周炎以及其他全身性疾病相关的革兰氏阴性细菌。这种生物体产生许多毒力因子,所有这些毒力因子都为细菌提供了一些优势。几项研究表明,从患病患者(尤其是非洲裔患者)中分离出来的临床菌株通常属于伴放线放线菌的特定克隆,这些克隆会产生明显更高量的属于毒素重复序列 (RTX) 家族的蛋白质外毒素,即白细胞毒素。 LtxA),而来自健康患者的分离株则含有最低限度的白细胞毒性菌株。这一发现表明,LtxA 可能在A. actinomycetemcomitans 的致病性中发挥关键作用。由于这种相关性,过去 30 年的许多工作都集中在了解 LtxA 与宿主细胞相互作用并杀死宿主细胞的机制上。在本文中,我们回顾了这些发现,强调了剩余的悬而未决的问题,并展示了对这些机制的了解,特别是毒素与淋巴细胞功能相关抗原 1 (LFA-1) 和胆固醇的相互作用,如何能够设计靶向抗LtxA 预防/治疗疾病的策略。
更新日期:2020-03-10
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