Department of Microbiology and Immunology, University at Buffalo, the State University of New York, Buffalo, New York, USA.
Clinical and Translational Research Center, University at Buffalo, the State University of New York, Buffalo, New York, USA.
Infect Immun. 2019 Oct 18;87(11). doi: 10.1128/IAI.00462-19. Print 2019 Nov.
Nontypeable (NTHi) is the primary cause of bacterially induced acute exacerbations of chronic obstructive pulmonary disease (COPD). NTHi adheres to and invades host respiratory epithelial cells as a means to persist in the lower airways of adults with COPD. Therefore, we mined the genomes of NTHi strains isolated from the airways of adults with COPD to identify novel proteins to investigate their role in adherence and invasion of human respiratory epithelial cells. An isogenic knockout mutant of the open reading frame showed a 76.6% ± 5.5% reduction in invasion of human bronchial and alveolar epithelial cells at 1, 3, and 6 h postinfection. Decreased invasion of the mutant was independent of either intracellular survival or adherence to cells. is conserved among NTHi genomes. Results of whole-bacterial-cell enzyme-linked immunosorbent assay (ELISA) and flow cytometry experiments identified that NTHI1441 has epitopes expressed on the bacterial cell surface. Adults with COPD develop increased serum IgG against NTHI1441 after experiencing an exacerbation with NTHi. This study reveals NTHI1441 as a novel NTHi virulence factor expressed during infection of the COPD lower airways that contributes to invasion of host respiratory epithelial cells. The role in host cell invasion, conservation among strains, and expression of surface-exposed epitopes suggest that NTHI1441 is a potential target for preventative and therapeutic interventions for disease caused by NTHi.
不可分型流感嗜血杆菌（NTHi）是引起慢性阻塞性肺疾病（COPD）急性加重的主要原因。NTHi 附着并侵入宿主呼吸道上皮细胞，以此在 COPD 患者的下呼吸道中持续存在。因此，我们对从 COPD 患者气道中分离的 NTHi 菌株的基因组进行了挖掘，以鉴定新的蛋白，研究其在人呼吸道上皮细胞黏附和侵袭中的作用。ORF 的基因敲除突变体显示，在感染后 1、3 和 6 小时，对人支气管和肺泡上皮细胞的侵袭减少了 76.6%±5.5%。突变体侵袭减少与细胞内存活或细胞黏附无关。在 NTHi 基因组中保守。全细菌细胞酶联免疫吸附试验（ELISA）和流式细胞术实验的结果表明，NTHI1441 具有在细菌细胞表面表达的表位。患有 COPD 的成年人在经历 NTHi 引起的加重后，针对 NTHI1441 的血清 IgG 增加。这项研究揭示了 NTHI1441 是一种新型的 NTHi 毒力因子，在 COPD 下呼吸道感染期间表达，有助于宿主呼吸道上皮细胞的侵袭。在宿主细胞侵袭中的作用、菌株间的保守性以及表面暴露表位的表达表明，NTHI1441 是预防和治疗 NTHi 引起疾病的潜在靶点。
