The Staphylococcus aureus CidA and LrgA Proteins Are Functional Holins Involved in the Transport of By-Products of Carbohydrate Metabolism.

The Staphylococcus aureus CidA and LrgA Proteins Are Functional Holins Involved in the Transport of By-Products of Carbohydrate Metabolism.
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DOI:
10.1128/mbio.02827-21
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发表时间:
2021-02-22
期刊:
影响因子:
6.4
通讯作者:
Bayles KW
Bayles KW
中科院分区:
生物学1区
文献类型:
--
作者:
Endres JL;Chaudhari SS;Zhang X;Prahlad J;Wang SQ;Foley LA;Luca S;Bose JL;Thomas VC;Bayles KW

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金黄色葡萄球菌CIDABC和lrgAB操纵子编码一个保守的蛋白质家族的成员,被认为参与了细胞程序性死亡(PCD)。基于CIDA和LrgA与噬菌体Holins在结构上的相似性,我们假设这些蛋白通过在细胞膜内形成孔来发挥功能。为了测试这一点,我们使用了一个“裂解盒”系统,该系统展示了CIDA和lrgA基因支持噬菌体内毒素诱导的细胞裂解的能力。典型的Holin蛋白,CIDA和LrgA诱导的裂解依赖于内溶素的共表达,这与这些蛋白的Holin样功能是一致的。此外,CIDA和LrgA蛋白被证明定位于膜小泡的表面,并导致小分子的泄漏,为其形成孔的潜力提供了直接的证据。与最近报道的其他细菌和植物中的lrgAB同系物在碳水化合物代谢副产物的运输中所起的作用相一致,我们还表明lrgAB在微氧和厌氧生长过程中通过促进丙酮酸的摄取,对金黄色葡萄球菌利用丙酮酸是重要的。综上所述,这些数据揭示了CIDA和LrgA膜蛋白具有Holin样属性,这些属性在碳水化合物代谢的小副产物的运输中发挥着重要作用。
The Staphylococcus aureus cidABC and lrgAB operons encode members of a well-conserved family of proteins thought to be involved in programmed cell death (PCD). Based on the structural similarities that CidA and LrgA share with bacteriophage holins, we have hypothesized that these proteins function by forming pores within the cytoplasmic membrane. To test this, we utilized a “lysis cassette” system that demonstrated the abilities of the cidA and lrgA genes to support bacteriophage endolysin-induced cell lysis. Typical of holins, CidA- and LrgA-induced lysis was dependent on the coexpression of endolysin, consistent with the proposed holin-like functions of these proteins. In addition, the CidA and LrgA proteins were shown to localize to the surface of membrane vesicles and cause leakage of small molecules, providing direct evidence of their hole-forming potential. Consistent with recent reports demonstrating a role for the lrgAB homologues in other bacterial and plant species in the transport of by-products of carbohydrate metabolism, we also show that lrgAB is important for S. aureus to utilize pyruvate during microaerobic and anaerobic growth, by promoting the uptake of pyruvate under these conditions. Combined, these data reveal that the CidA and LrgA membrane proteins possess holin-like properties that play an important role in the transport of small by-products of carbohydrate metabolism.
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