The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages

The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages
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DOI:
10.1128/iai.05443-11
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发表时间:
2012-05-01
影响因子:
3.1
通讯作者:
May, Robin C.
May, Robin C.
中科院分区:
医学2区
文献类型:
--
作者:
Cumley, Nicola J.;Smith, Leanne M.;May, Robin C.

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B族链球菌(GBS)是新生儿脑膜炎和败血症的主要原因。这种生物体在吞噬细胞内生存的能力知之甚少,但被认为是在宿主中建立疾病的重要步骤。在这里,我们证明了GBS在J774巨噬细胞内的存活时间延长,并且在代表不同血清型、多位点序列类型(MLST)和临床分离位点的各种菌株中,存活能力没有显著变化。使用染色的溶酶体相关膜蛋白(LAMP)和吞噬体酸化的药理学抑制,我们表明,链球菌驻留在吞噬体和吞噬体的酸化是GBS细胞内生存所需的。此外,我们表明,GBS双组分系统CovS/CovR,这是在这种生物体中的主要酸反应调节剂,是必需的吞噬体内的生存。
Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and septicemia. The ability of this organism to survive inside phagocytic cells is poorly understood but thought to be an important step for the establishment of disease in the host. Here, we demonstrate that GBS shows prolonged survival within J774 macrophages and that the capacity to survive is not significantly changed across a diverse range of strains representing different serotypes, multilocus sequence types (MLST), and sites of clinical isolation. Using staining for the lysosome-associated membrane protein (LAMP) and by pharmacological inhibition of phagosome acidification, we demonstrate that streptococci reside in a phagosome and that acidification of the phagosome is required for GBS to survive intracellularly. Moreover, we show that the GBS two-component system CovS/CovR, which is the major acid response regulator in this organism, is required for survival inside the phagosome.