Conditional impairment of Coxiella burnetii by glucose-6P dehydrogenase activity.
Pathog Dis
; 79(6)2021 07 20.
Article
em En
| MEDLINE
| ID: mdl-34259815
ABSTRACT
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 â¼2 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Febre Q
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Coxiella burnetii
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Glucosefosfato Desidrogenase
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NADP
Limite:
Animals
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Humans
Idioma:
En
Revista:
Pathog Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos