Mammalian Cell Entry domains are required for bile resistance and virulence in Salmonella

Mammalian Cell Entry domains are required for bile resistance and virulence in Salmonella
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沙门氏菌的胆汁抗性和毒力需要哺乳动物细胞进入结构域

DOI:
10.1101/263871
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发表时间:
2018
期刊:
--
影响因子:
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通讯作者:
Isom G
Isom G
中科院分区:
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作者:
Isom G

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MCE结构域首先在分枝杆菌中报道,在哺乳动物细胞进入中起作用,随后的研究表明它们在感染过程中的重要性。在这里,我们研究了MCE蛋白在鼠伤寒沙门氏菌感染哺乳动物过程中的功能。我们报告称,MCE蛋白是沙门氏菌毒力所需的,但这与哺乳动物细胞粘附、进入或存活的降低无关。相反,我们发现MCE蛋白是沙门氏菌耐药性所必需的,特别是耐受胆汁盐如胆酸盐和脱氧胆酸盐。基于我们以前在大肠杆菌中的工作,以及其他报道MCE蛋白在膜生物发生中的作用的研究,我们提出Salmonellalacking MCE结构域具有缺陷的外膜,导致胆汁敏感性和体内毒性降低。这些结果表明,MCE结构域介导细菌膜生理学的基本方面,而不是在哺乳动物细胞进入中的直接作用,解释了它们在致病性和非致病性细菌中的保守性。
MCE domains were first reported inMycobacteriaas having a role inMammalianCellEntry, with subsequent studies showing their importance during infection. Here, we have examined the function of MCE proteins inSalmonellaTyphimurium during mammalian infection. We report that MCE proteins are required forSalmonellavirulence, but that this is not related to decreased adherence, entry or survival in mammalian cells. Instead, we reveal that MCE proteins are required forSalmonellabile resistance, in particular to withstand bile salts such as cholate and deoxycholate. Based on our previous work inEscherichia coli, and other studies that have reported roles for MCE proteins in membrane biogenesis, we propose thatSalmonellalacking MCE domains have a defective outer membrane that results in bile sensitivity and decreased virulencein vivo. These results suggest that MCE domains mediate fundamental aspects of bacterial membrane physiology as opposed to a proposed direct role in mammalian cell entry, explaining their conservation across both pathogenic and non-pathogenic bacteria.
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