Ferrochelatase is present in Brucella abortus and is critical for its intracellular survival and virulence

被引:39
作者
Almirón, M
Martínez, M
Sanjuan, N
Ugalde, RA
机构
[1] UNSAM, CONICET, INTECH, IIB, RA-1650 Buenos Aires, DF, Argentina
[2] Univ Buenos Aires, Fac Med, Dept Microbiol, Lab Patol Expt, Buenos Aires, DF, Argentina
关键词
D O I
10.1128/IAI.69.10.6225-6230.2001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Brucella spp. are pathogenic bacteria that cause brucellosis, an animal disease which can also affect humans. Although understanding the pathogenesis is important for the health of animals and humans, little is known about virulence factors associated with it. In order for chronic disease to be established, Brucella spp. have developed the ability to survive inside phagocytes by evading cell defenses. It hides inside vacuoles, where it then replicates, indicating that it has an active metabolism. The purpose of this work was to obtain better insight into the intracellular metabolism of Brucella abortus. During a B. abortus genomic sequencing project, a clone coding a putative gene homologous to hemH was identified and sequenced. The amino acid sequence revealed high homology to members of the ferrochelatase family. A knockout mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALB/c mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B. abortus synthesizes its own heme and also has the ability to use an external source of heme; however, inside cells, there is not enough available heme to support its intracellular metabolism. It is concluded that ferrochelatase is essential for the multiplication and intracellular survival of B. abortus and thus for the establishment of chronic disease as well.
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页码:6225 / 6230
页数:6
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