Coxiella burnetii is a bacterial obligate intracellular parasite and the etiological agent of query (Q) fever. While the C. burnetii genome has been reduced to ∼2 Mb as a likely consequence of genome streamlining in response to parasitism, enzymes for a nearly complete central metabolic machinery are encoded by the genome. However, lack of a canonical hexokinase for phosphorylation of glucose and an apparent absence of the oxidative branch of the pentose phosphate pathway, a major mechanism for regeneration of the reducing equivalent nicotinamide adenine dinucleotide phosphate (NADPH), have been noted as potential metabolic limitations of C. burnetii. By complementing C. burnetii with the gene zwf encoding the glucose-6-phosphate-consuming and NADPH-producing enzyme glucose-6-phosphate dehydrogenase (G6PD), we demonstrate a severe metabolic fitness defect for C. burnetii under conditions of glucose limitation. Supplementation of the medium with the gluconeogenic carbon source glutamate did not rescue the growth defect of bacteria complemented with zwf. Absence of G6PD in C. burnetii therefore likely relates to the negative effect of its activity under conditions of glucose limitation. Coxiella burnetii central metabolism with emphasis on glucose, NAD+, NADP+ and NADPH is discussed in a broader perspective, including comparisons with other bacterial obligate intracellular parasites.

中文翻译：

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葡萄糖-6P脱氢酶活性对伯氏柯克氏体的条件性损害

Coxiella burnetii 是一种细菌专性细胞内寄生虫和查询 (Q) 热的病原体。虽然作为响应寄生的基因组精简的可能结果，C. burnetii 基因组已减少到~2 Mb，但几乎完整的中央代谢机制的酶由基因组编码。然而，缺乏用于葡萄糖磷酸化的经典己糖激酶和明显缺乏戊糖磷酸途径的氧化分支，这是还原等效烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 再生的主要机制，已被认为是潜在的代谢限制。 C.伯内特。通过用编码消耗葡萄糖 6 磷酸和产生 NADPH 的酶葡萄糖 6 磷酸脱氢酶 (G6PD) 的基因 zwf 补充伯氏梭菌，我们证明了在葡萄糖限制条件下 C. burnetii 的严重代谢适应性缺陷。用糖异生碳源谷氨酸补充培养基并不能挽救用 zwf 补充的细菌的生长缺陷。因此，C. burnetii 中 G6PD 的缺失可能与其在葡萄糖限制条件下活性的负面影响有关。从更广泛的角度讨论了以葡萄糖、NAD+、NADP+ 和 NADPH 为重点的 Coxiella burnetii 中枢代谢，包括与其他细菌专性细胞内寄生虫的比较。因此，burnetii 可能与其在葡萄糖限制条件下活性的负面影响有关。从更广泛的角度讨论了以葡萄糖、NAD+、NADP+ 和 NADPH 为重点的 Coxiella burnetii 中枢代谢，包括与其他细菌专性细胞内寄生虫的比较。因此，burnetii 可能与其在葡萄糖限制条件下活性的负面影响有关。从更广泛的角度讨论了以葡萄糖、NAD+、NADP+ 和 NADPH 为重点的 Coxiella burnetii 中枢代谢，包括与其他细菌专性细胞内寄生虫的比较。