A Functional Slow Recycling Pathway of Transferrin is Required for Growth of Chlamydia.

A Functional Slow Recycling Pathway of Transferrin is Required for Growth of Chlamydia.
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DOI:
10.3389/fmicb.2010.00112
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发表时间:
2010
影响因子:
5.2
通讯作者:
Carabeo RA
Carabeo RA
中科院分区:
生物学2区
文献类型:
--
作者:
Ouellette SP;Carabeo RA

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一种宿主细胞溶血磷脂酰基转移酶(一种参与脂质代谢的酶)的抑制剂,通过其对转铁蛋白(Tf)的转运(经由缓慢的再循环途径)的作用来阻断专性细胞内病原体衣原体的生长。这种抑制的详细表征表明,Tf积累在囊泡Rab 11阳性,与运输中间Rab 4/11杂交囊泡内发现的Tf水平的同时减少。最终结果是不能再循环到质膜。在衣原体感染的细胞中,含有Tf的Rab 11阳性囊泡通常与包涵体密切相关,用抑制剂处理会导致其积累,这表明Tf循环的及时进展和完成对于衣原体的适当生长是必要的。生长抑制的化合物可以被否定的简单的去除含Tf的部分的血清,进一步表明,周围的衣原体夹杂物的Tf的积累是有害的病原体。因此,似乎操纵缓慢的再循环途径可能对衣原体产生生物学后果,并意味着需要仔细调节包涵体与宿主运输途径的相互作用。
An inhibitor of host cell lysophospholipid acyltransferase, an enzyme involved in lipid metabolism blocked growth of the obligate intracellular pathogen Chlamydia through its action on the transport of transferrin (Tf) via the slow pathway of recycling. A detailed characterization of this inhibition revealed that Tf accumulated in vesicles positive for Rab11, with a concomitant reduction in the level of Tf found within the transport intermediate Rab4/11 hybrid vesicles. The net result was the failure to be recycled to the plasma membrane. In chlamydiae-infected cells, the Tf-containing Rab11-positive vesicles were typically found intimately associated with the inclusion, and treatment with the inhibitor caused their accumulation, suggesting that the timely progression and completion of Tf recycling was necessary for proper chlamydial growth. Growth inhibition by the compound could be negated by the simple removal of the Tf-containing fraction of the serum, a further indication that accumulation of Tf around the chlamydial inclusion was deleterious to the pathogen. Thus, it appears that manipulating the slow recycling pathway can have biological consequences for Chlamydia and implies the need to regulate carefully the interaction of the inclusion with this host trafficking pathway.
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