Conditional impairment of Coxiella burnetii by glucose-6P dehydrogenase activity.
Conditional impairment of Coxiella burnetii by glucose-6P dehydrogenase activity.
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DOI：
10.1093/femspd/ftab034
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发表时间：
2021-07-20
影响因子：
3.3
通讯作者：
Omsland A
中科院分区：
文献类型：
--
作者：
Sanchez SE;Omsland A
伯内特柯克斯体是一种细菌专性细胞内寄生虫，也是查询热 (Q) 的病原体。虽然 C. burnetii 基因组已减少至~2 Mb，这可能是响应寄生的基因组精简的结果，但几乎完整的中央代谢机制的酶是由基因组编码的。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，这是还原性等价烟酰胺腺嘌呤二核苷酸磷酸（NADPH）再生的主要机制，已被认为是伯内特衣藻的潜在代谢限制。通过用编码葡萄糖 6-磷酸消耗和 NADPH 产生酶葡萄糖 6-磷酸脱氢酶 (G6PD) 的基因 zwf 补充伯内特氏菌，我们证明了伯内特氏菌在葡萄糖限制条件下存在严重的代谢适应性缺陷。在培养基中添加糖异生碳源谷氨酸并不能挽救补充了zwf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伯内特立克斯体的中枢代谢，重点是葡萄糖、NAD+、NADP+ 和 NADPH，包括与其他细菌专性细胞内寄生虫的比较。伯内氏立克次体中基因 zwf 的表达是 NADPH 再生的主要机制，会导致有条件的生长障碍。
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. Expression of the gene zwf, a major mechanism for regenerating NADPH, in Coxiella burnetii leads to conditional impairment of growth.
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影响因子：
6.4
作者：
Beare PA;Gilk SD;Larson CL;Hill J;Stead CM;Omsland A;Cockrell DC;Howe D;Voth DE;Heinzen RA
通讯作者：
Heinzen RA
影响因子：
3.2
作者：
Audia, Jonathon P.;Winkler, Herbert H.
通讯作者：
Winkler, Herbert H.
影响因子：
4.1
作者：
Kuba, Miku;Neha, Nitika;Newton, Hayley J.
通讯作者：
Newton, Hayley J.
影响因子：
3.4
作者：
Bitew, Mebratu A.;Hofmann, Janine;Sansom, Fiona M.
通讯作者：
Sansom, Fiona M.
影响因子：
4.8
作者：
Bitew, Mebratu A.;Khoo, Chen Ai;Sansom, Fiona M.
通讯作者：
Sansom, Fiona M.