Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, 240 S. 40th St., Philadelphia, PA 19104, USA.
Int J Mol Sci. 2022 Oct 20;23(20):12598. doi: 10.3390/ijms232012598.
The pertussis agent produces a number of virulence factors, of which the filamentous hemagglutinin (FhaB) plays a role in adhesion to epithelial and phagocytic cells. Moreover, FhaB was recently found to play a crucial role in nasal cavity infection and transmission to new hosts. The 367 kDa FhaB protein translocates through an FhaC pore to the outer bacterial surface and is eventually processed to a ~220 kDa N-terminal FHA fragment by the SphB1 protease. A fraction of the mature FHA then remains associated with bacterial cell surface, while most of FHA is shed into the bacterial environment. Previously reported indirect evidence suggested that FHA, or its precursor FhaB, may bind the β integrin CD11b/CD18 of human macrophages. Therefore, we assessed FHA binding to various cells producing or lacking the integrin and show that purified mature FHA does not bind CD11b/CD18. Further results then revealed that the adhesion of to cells does not involve an interaction between the bacterial surface-associated FhaB and/or mature FHA and the β integrin CD11b/CD18. In contrast, FHA binding was strongly inhibited at micromolar concentrations of heparin, corroborating that the cell binding of FHA is ruled by the interaction of its heparin-binding domain with sulfated glycosaminoglycans on the cell surface.
百日咳菌产生许多毒力因子，其中丝状血凝素（FhaB）在黏附上皮和吞噬细胞中起作用。此外，最近发现 FhaB 在鼻腔感染和向新宿主传播中起着至关重要的作用。367 kDa 的 FhaB 蛋白通过 FhaC 孔转运到细菌外表面，并最终被 SphB1 蛋白酶加工成~220 kDa 的 N 端 FHA 片段。成熟 FHA 的一部分仍然与细菌表面相关联，而大部分 FHA 则脱落到细菌环境中。先前报道的间接证据表明，FHA 或其前体 FhaB 可能与人类巨噬细胞的β整合素 CD11b/CD18 结合。因此，我们评估了 FHA 与产生或缺乏整合素的各种细胞的结合情况，并表明纯化的成熟 FHA 不与 CD11b/CD18 结合。进一步的结果表明，与细胞的黏附不涉及细菌表面相关 FhaB 和/或成熟 FHA 与 β 整合素 CD11b/CD18 之间的相互作用。相比之下，肝素在微摩尔浓度下强烈抑制 FHA 的结合，这证实了 FHA 的细胞结合受其肝素结合域与细胞表面硫酸化糖胺聚糖相互作用的控制。
