RegR, a global LacI/GalR family regulator, modulates virulence and competence in Streptococcus pneumoniae
RegR, a global LacI/GalR family regulator, modulates virulence and competence in Streptococcus pneumoniae
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DOI：
10.1128/iai.71.5.2615-2625.2003
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发表时间：
2003-05-01
影响因子：
3.1
通讯作者：
Trombe, MC
中科院分区：
文献类型：
--
作者：
Chapuy-Regaud, S;Ogunniyi, AD;Trombe, MC
同型乳酸和过氧化氢酶缺陷型病原体肺炎链球菌不仅耐氧，而且需要其NADH氧化酶Nox的活性来发展最佳的毒力和遗传转化能力。在这项工作中，我们表明，全球监管RegR也参与了这些特征。遗传解剖显示，RegR调节能力和毒力因子的表达，包括透明质酸酶。在体外生长的细菌中，RegR抑制透明质酸酶。在中性pH下，它增加对A549上皮细胞的粘附，在碱性pH下，它作用于CiaRH双组分信号传导系统的上游以激活感受态。这些表型与抗生素耐药性、中枢代谢和碳水化合物利用的变化无关。尽管RegR（0）（其中0表示蛋白质的丧失）突变足以减弱菌株23477在小鼠中的实验毒力，但在RegR（0）菌株23302中引入额外的hyl（0）（其中0表示功能丧失）突变显著降低了其毒力。这表明RegR（0）Hyl（+）衍生物的残留毒力是由于透明质酸酶，并支持RegR在毒力中的双重作用。这种LacI/GaIR调节剂，在富培养基中的体外生长不是必需的，确实通过其控制能力，粘附性和毒力参与肺炎球菌的适应性反应。
The homolactic and catalase-deficient pathogen Streptococcus pneumoniae is not only tolerant to oxygen but requires the activity of its NADH oxidase, Nox, to develop optimal virulence and competence for genetic transformation. In this work, we show that the global regulator RegR is also involved in these traits. Genetic dissection revealed that RegR regulates competence and the expression of virulence factors, including hyaluronidase. In bacteria grown in vitro, RegR represses hyaluronidase. At neutral pH, it increases adherence to A549 epithelial cells, and at alkaline pH, it acts upstream of the CiaRH two-component signaling system to activate competence. These phenotypes are not associated with changes in antibiotic resistance, central metabolism, and carbohydrate utilization. Although the RegR(0) (where 0 indicates the loss of the protein) mutation is sufficient to attenuate experimental virulence of strain 23477 in mice, the introduction of an additional hyl(0) (where 0 indicates the loss of function) mutation in the RegR(0) strain 23302 dramatically reduces its virulence. This indicates that residual virulence of the RegR(0) Hyl(+) derivative is due to hyaluronidase and supports the dual role of RegR in virulence. This LacI/GaIR regulator, not essential for in vitro growth in rich media, is indeed involved in the adaptive response of the pneumococcus via its control of competence, adherence, and virulence.