Zinc uptake by Streptococcus pneumoniae depends on both AdcA and AdcAII and is essential for normal bacterial morphology and virulence
Zinc uptake by Streptococcus pneumoniae depends on both AdcA and AdcAII and is essential for normal bacterial morphology and virulence
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DOI：
10.1111/j.1365-2958.2011.07862.x
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发表时间：
2011-11-01
影响因子：
3.6
通讯作者：
Durmort, Claire
中科院分区：
文献类型：
--
作者：
Bayle, Lucie;Chimalapati, Suneeta;Durmort, Claire
锌是活细胞必需的痕量金属。ABC转运蛋白AdcABC先前被证明是肺炎链球菌摄取锌所必需的。由于我们最近描述了AdcAII是另一种锌结合脂蛋白，我们研究了ADCA和AdcAII在肺炎链球菌锌代谢中的作用。ADCA或adcAII的缺失而不是phtD的缺失降低了肺炎链球菌对锌的摄取，adca和adcAII的双重突变进一步减少了锌的进口。对于Delta(adca/adcAII)突变体，在低锌浓度下，菌体生长和胞内锌浓度均显著降低。在缺锌条件下生长时，Delta(adca/adcAII)突变体表现出与异常隔膜有关的形态缺陷。补锌后，Delta(adca/adcAII)突变体的生长和形态得到恢复。Adca和adcAII双缺失可显著抑制肺炎链球菌在支气管肺泡灌洗液和人血清中的生长，防止肺炎链球菌在小鼠鼻咽定植、肺炎和败血症模型中的感染，而不改变被膜。综上所述，我们的结果表明，ADCA和AdcAII在特异性地将锌输入肺炎球菌中起着必要和多余的作用，并且这两种锌转运蛋白对于肺炎链球菌在感染期间的正常细胞分裂和生存是必需的。
Zinc is an essential trace metal for living cells. The ABC transporter AdcABC was previously shown to be required for zinc uptake by Streptococcus pneumoniae. As we have recently described AdcAII as another zinc-binding lipoprotein, we have investigated the role of both AdcA and AdcAII in S. pneumoniae zinc metabolism. Deletion of either adcA or adcAII but not phtD reduced S. pneumoniae zinc uptake, with dual mutation of both adcA and adcAII further decreasing zinc import. For the Delta(adcA/adcAII) mutant, growth and intracellular concentrations of zinc were both greatly reduced in low zinc concentration. When grown in zinc-deficient medium, the Delta(adcA/adcAII) mutant displayed morphological defects related to aberrant septation. Growth and morphology of the Delta(adcA/adcAII) mutant recovered after supplementation with zinc. Dual deletion of adcA and adcAII strongly impaired growth of the pneumococcus in bronchoalveolar lavage fluid and human serum, and prevented S. pneumoniae establishing infection in mouse models of nasopharyngeal colonization, pneumonia and sepsis without altering the capsule. Taken together, our results show that AdcA and AdcAII play an essential and redundant role in specifically importing zinc into the pneumococcus, and that both zinc transporters are required for proper cell division and for S. pneumoniae survival during infection.