Ouellette Scot P, Carabeo Rey A
Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College London London, UK.
Front Microbiol. 2010 Oct 8;1:112. doi: 10.3389/fmicb.2010.00112. eCollection 2010.
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.
宿主细胞溶血磷脂酰转移酶是一种参与脂质代谢的酶，一种该酶的抑制剂通过作用于转铁蛋白（Tf）经慢速再循环途径的转运，阻断了专性胞内病原体衣原体的生长。对这种抑制作用的详细表征显示，Tf在Rab11阳性的囊泡中积累，同时在转运中间体Rab4/11杂交囊泡中发现的Tf水平降低。最终结果是无法再循环至质膜。在衣原体感染的细胞中，含Tf的Rab11阳性囊泡通常与包涵体紧密相关，用抑制剂处理会导致它们积累，这表明Tf再循环的及时进展和完成对于衣原体的正常生长是必要的。通过简单去除血清中含Tf的部分，可以消除该化合物对生长的抑制作用，这进一步表明衣原体包涵体周围Tf的积累对病原体有害。因此，似乎操纵慢速再循环途径会对衣原体产生生物学影响，这意味着需要仔细调节包涵体与这种宿主运输途径的相互作用。
