Chlamydia exploit the mammalian tryptophan-depletion defense strategy as a counter-defensive cue to trigger a survival state of persistence.

Chlamydia exploit the mammalian tryptophan-depletion defense strategy as a counter-defensive cue to trigger a survival state of persistence.
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DOI:
10.3389/fcimb.2014.00017
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发表时间:
2014
影响因子:
5.7
通讯作者:
Jensen RA
Jensen RA
中科院分区:
医学2区
文献类型:
--
作者:
Bonner CA;Byrne GI;Jensen RA

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我们之前提出,在衣原科中,快速的营养生长和静止状态的生存(持久性)取决于宿主色氨酸(Trp)可用性所决定的替代蛋白质翻译谱。这些备选谱分别对应于一组衣原体蛋白具有高于预测的色氨酸含量(“上色氨酸”选择),或另一组衣原体蛋白具有低于预测的色氨酸含量(“下色氨酸”选择)。对衣原体科蛋白质组中色氨酸含量的比较评价现已扩展到衣原体目的其他分类单元科。在Order水平,Trp含量升高发生在核苷酸、s -腺苷甲硫氨酸(SAM)、二羧酸底物和Trp本身的转运体中。对于色氨酸和核苷酸转运体,由于广泛的平行扩展,这在其他衣原体科(副衣原体科,waddli科和Simkaniaceae)中更为明显。这表明细胞内色氨酸的可用性在衣原体共同祖先中作为增强或抑制衣原体代谢的古老生存线索。Chlamydiaceae家族进一步加强了对在细胞分裂、脂多糖生物合成和甲基转移酶反应中起作用的蛋白质的Up-Trp选择。一些表现出上链选择的蛋白质仅存在于衣原体科,例如细胞毒素和多态膜蛋白(Pmp's)的相似家族。衣原科中Down-Trp选择的一个显著例子是choris酸生物合成途径和连接的甲基萘醌途径。新发现的甲萘醌合成途径为1,4-二羟基-6-萘酚酸途径,而其他衣原体科的甲萘醌合成途径为经典的2-萘酚酸途径。由于极端的Down-Trp选择,甲基萘醌的生物合成似乎对在严重Trp限制条件下维持持续状态的完整性尤为重要,因此可能对慢性疾病状态的延续至关重要。
We previously proposed that in Chlamydiaceae rapid vegetative growth and a quiescent state of survival (persistence) depend upon alternative protein translational profiles dictated by host tryptophan (Trp) availability. These alternative profiles correspond, respectively, with a set of chlamydial proteins having higher-than-predicted contents of Trp (“Up-Trp” selection), or with another set exhibiting lower-than-predicted contents of Trp (“Down-Trp” selection). A comparative evaluation of Chlamydiaceae proteomes for Trp content has now been extended to a number of other taxon families within the Chlamydiales Order. At the Order level, elevated Trp content occurs for transporters of nucleotides, S-adenosylmethionine (SAM), dicarboxylate substrates, and Trp itself. For Trp and nucleotide transporters, this is even more pronounced in other chlamydiae families (Parachlamydiaceae, Waddliaceae, and Simkaniaceae) due to extensive paralog expansion. This suggests that intracellular Trp availability served as an ancient survival cue for enhancement or restraint of chlamydial metabolism in the common Chlamydiales ancestor. The Chlamydiaceae Family further strengthened Up-Trp selection for proteins that function in cell division, lipopolysaccharide biosynthesis, and methyltransferase reactions. Some proteins that exhibit Up-Trp selection are uniquely present in the Chlamydiaceae, e.g., cytotoxin and the paralog families of polymorphic membrane proteins (Pmp's). A striking instance of Down-Trp selection in the Chlamydiaceae is the chorismate biosynthesis pathway and the connecting menaquinone pathway. The newly recognized 1,4-dihydroxy-6-napthoate pathway of menaquinone biosynthesis operates in Chlamydiaceae, whereas the classic 2-napthoate pathway is used in the other Chlamydiales families. Because of the extreme Down-Trp selection, it would appear that menaquinone biosynthesis is particularly important to the integrity of the persistent state maintained under conditions of severe Trp limitation, and may thus be critical for perpetuation of chronic disease states.
DOI: 10.1126/science.1201711
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期刊: SCIENCE
影响因子: 56.9
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