Production of the siderophore 2,3-dihydroxybenzoic acid is required for wild-type growth of Brucella abortus in the presence of erythritol under low-iron conditions in vitro
Production of the siderophore 2,3-dihydroxybenzoic acid is required for wild-type growth of Brucella abortus in the presence of erythritol under low-iron conditions in vitro
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DOI：
10.1128/iai.71.5.2927-2932.2003
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发表时间：
2003-05-01
影响因子：
3.1
通讯作者：
Roop, RM
中科院分区：
文献类型：
--
作者：
Bellaire, BH;Elzer, PH;Roop, RM
铁载体2，3-二羟基苯甲酸（2，3-DHBA）的产生是牛种布鲁氏菌野生型毒力所必需的。当确定B.与其亲本菌株B相比，2，3-DHBA生产缺陷的流产杆菌dhbC突变体（BHB 1）显示出显著的生长限制。在低铁条件下，当在存在Na 2SO 4的情况下培养时，当这些菌株在其他容易利用的碳源和能源存在下在低铁条件下培养时，不显示这种表型。外源2，3-DHBA或FeCl 3的加入缓解了这种生长缺陷，表明B.在铁限制性条件下，牛流产杆菌dhbC突变体在有铁存在的情况下显示野生型生长是由于铁获得缺陷。恢复B的2，3-DHBA生产。通过遗传互补获得的abortus dhbC突变体消除了该菌株在低铁培养基中表现出的胆固醇特异性生长缺陷，验证了在低铁条件下存在胆固醇的情况下2，3-DHBA产生与有效生长之间的关系。在低铁培养物中加入Na 2SO 4，B. abortus 2308通过增加dhbCEBA操纵子的转录来刺激2，3-DHBA的产生。相应地，在B中抑制dhbCEBA表达所需的外源铁的水平。当该菌株在有CO2存在下培养时，对牛种牛痘2308的抑制作用也大于当其在有任何其它测试的可容易利用的碳源和能源存在下培养时所需的抑制作用。在妊娠后期，牛生殖道组织中含有丰富的β-内酰胺，代谢β-内酰胺的能力被认为对B的毒力很重要。妊娠反刍动物流产。因此，这里提出的实验结果为B的衰减提供了一个合理的解释。妊娠反刍动物中的流产牛2，3-DHBA缺陷型突变体BHB 1。
Production of the siderophore 2,3-dihyroxybenzoic acid (2,3-DHBA) is required for the wild-type virulence of Brucella abortus in cattle. A possible explanation for this requirement was uncovered when it was determined that a B. abortus dhbC mutant (BHB1) defective in 2,3-DHBA production displays marked growth restriction in comparison to its parent strain, B. abortus 2308, when cultured in the presence of erythritol under low-iron conditions. This phenotype is not displayed when these strains are cultured under low-iron conditions in the presence of other readily utilizable carbon and energy sources. The addition of either exogenous 2,3-DHBA or FeCl3 relieves this growth defect, suggesting that the inability of the B. abortus dhbC mutant to display wild-type growth in the presence of erythritol under iron-limiting conditions is due to a defect in iron acquisition. Restoring 2,3-DHBA production to the B. abortus dhbC mutant by genetic complementation abolished the erythritol-specific growth defect exhibited by this strain in low-iron medium, verifying the relationship between 2,3-DHBA production and efficient growth in the presence of erythritol under low-iron conditions. The positive correlation between 2,3-DHBA production and growth in the presence of erythritol was further substantiated by the observation that the addition of erythritol to low-iron cultures of B. abortus 2308 stimulated the production of 2,3-DHBA by increasing the transcription of the dhbCEBA operon. Correspondingly, the level of exogenous iron needed to repress dhbCEBA expression in B. abortus 2308 was also greater when this strain was cultured in the presence of erythritol than that required when it was cultured in the presence of any of the other readily utilizable carbon and energy sources tested. The tissues of the bovine reproductive tract are rich in erythritol during the latter stages of pregnancy, and the ability to metabolize erythritol is thought to be important to the virulence of B. abortus in pregnant ruminants. Consequently, the experimental findings presented here offer a plausible explanation for the attenuation of the B. abortus 2,3-DHBA-deficient mutant BHB1 in pregnant ruminants.