Comparison of Biological Activities of BafA Family Autotransporters within <i>Bartonella</i> Species Derived from Cats and Rodents
Comparison of Biological Activities of BafA Family Autotransporters within <i>Bartonella</i> Species Derived from Cats and Rodents
复制标题
猫和啮齿类动物巴尔通体物种中 BafA 家族自转运蛋白的生物活性比较
DOI：
10.1128/iai.00186-22
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发表时间：
2023
影响因子：
3.1
通讯作者：
Tsukamoto Kentaro
中科院分区：
文献类型：
--
作者：
Kumadaki Kayo;Suzuki Natsumi;Tatematsu Kaoru;Doi Yohei;Tsukamoto Kentaro
巴尔通体属是嗜血性、兼性细胞内细菌，其中一些引起人畜共患病，在包括人类在内的许多哺乳动物中广泛传播。在人类感染过程中，血管内皮细胞作为巴尔通体的复制生态位发挥着至关重要的作用，其中一些细胞能够促进血管增殖。除了经过充分研究的致病因子（例如三聚体自转运蛋白粘附素 BadA 或 VirB/D4 IV 型分泌系统）之外，细菌分泌蛋白 BafA 也参与巴尔通体诱导的血管增殖。编码 BafA 直向同源物的基因已在大多数巴尔通体物种的基因组中发现，但其功能仍不清楚。在这项研究中，我们重点关注了三种源自猫的人畜共患物种（B. henselae、B. koehlerae 和 B. clarridgeiae）和两种源自啮齿动物的物种（B. grahamii 和 B. doshiae），并比较了源自每个物种的 BafA 活性。 B. henselae、B. koehlerae、B. clarridgeiae 和 B. grahamii 等物种的重组 BafA 蛋白也会引起人类疾病，诱导培养的内皮细胞中的细胞增殖和管形成，而源自 B. doshiae 的 BafA 蛋白（一种在人类中很少发现的物种）则没有表现出这两种活性。此外，用这些 BafA 蛋白处理细胞会增加血管内皮生长因子受体 2 和细胞外信号调节激酶 1/2 的磷酸化，但 B. doshiae BafA 除外。物种间bafAmRNA表达和BafA分泌的差异可能导致细菌感染细胞的细胞增殖表型的差异。这些发现表明，BafA 的生物活性可能与巴尔通体在人类中的感染性或致病性有关。
Bartonellaspecies are hemotropic, facultative intracellular bacteria, some of which cause zoonoses, that are widely disseminated among many mammals, including humans. During infection in humans, vascular endothelial cells play a crucial role as a replicative niche forBartonella, and some are capable of promoting vascular proliferation. Along with well-studied pathogenic factors such as a trimeric autotransporter adhesin BadA or VirB/D4 type IV secretion system, bacteria-secreted protein BafA is also involved inBartonella-induced vasoproliferation. Genes encoding BafA orthologs have been found in the genomes of mostBartonellaspecies, but their functionality remains unclear. In this study, we focused on three cat-derived zoonotic species (B. henselae, B. koehlerae, and B. clarridgeiae) and two rodent-derived species (B. grahamii and B. doshiae) and compared the activity of BafA derived from each species. Recombinant BafA proteins of B. henselae, B. koehlerae, B. clarridgeiae, and B. grahamii, species that also cause human disease, induced cell proliferation and tube formation in cultured endothelial cells, while BafA derived from B. doshiae, a species that is rarely found in humans, showed neither activity. Additionally, treatment of cells with these BafA proteins increased phosphorylation of both vascular endothelial growth factor receptor 2 and extracellular signal-regulated kinase 1/2, with the exception of B. doshiae BafA. DifferentialbafAmRNA expression and BafA secretion among the species likely contributed to the differences in the cell proliferation phenotype of the bacteria-infected cells. These findings suggest that the biological activity of BafA may be involved in the infectivity or pathogenicity ofBartonellaspecies in humans.