A novel SigB(Q225P) mutation in Staphylococcus aureus retains virulence but promotes biofilm formation.
A novel SigB(Q225P) mutation in Staphylococcus aureus retains virulence but promotes biofilm formation.
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金黄色葡萄球菌中的一种新的 SigB(Q225P) 突变保留了毒力，但促进了生物膜的形成
DOI：
10.1038/s41426-018-0078-1
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发表时间：
2018-04-25
影响因子：
13.2
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Liu H;Shang W;Hu Z;Zheng Y;Yuan J;Hu Q;Peng H;Cai X;Tan L;Li S;Zhu J;Li M;Hu X;Zhou R;Rao X;Yang Y
金黄色葡萄球菌（Staphylococcus aureus）是一种重要的致病菌，其毒力因子丰富，可引起多种疾病，严重威胁人类健康。压力反应调节子被称为sigma因子B（SigB），是一个被充分表征的全局调节子，参与了S.金黄色葡萄球菌毒力、色素沉着和生物膜形成。然而，S.对金黄色葡萄球菌的描述不完全。在这里，我们发现了一个新的替代突变，SigB（Q225 P），它有助于S的非色素表型。金黄色。色葡萄携带SigB（Q225 P）取代的金黄色葡萄球菌突变体缺乏葡萄球菌黄素，葡萄球菌黄素是保护细菌免受宿主氧化剂杀死的关键毒力因子，但保留了细菌致病性，毒力因子发生多效性改变，导致动物模型中相似的致死率和脓肿形成能力。我们还报道了SigB（Q225 P）促进S.金黄色。实时荧光定量PCR（RT-qPCR）结果显示，SigB（Q225 P）突变株编码热核酸酶的nuc基因表达显著下调，导致eDNA在生物膜中积累。LacZ报告基因分析表明，SigB（Q225 P）对nuc启动子的活性有影响。电泳迁移率变动分析（EMSA）和生物层干涉法（BLI）分析表明，SigB和SigB（Q225 P）蛋白均能与nuc基因启动子直接结合，而SigB（Q225 P）蛋白的结合活性降低。我们的数据更新了对S.金黄色葡萄球菌金黄色色素及其毒力的研究表明，SigB基因的单一取代突变可能促进了金黄色葡萄球菌生物膜的形成。金黄色葡萄球菌通过直接下调nuc表达。
Staphylococcus aureus is an important pathogen that produces abundant virulence factors, which cause various diseases that burden human health worldwide. The stress response regulon called sigma factor B (SigB) is a well-characterized global regulator that is involved in the regulation of S. aureus virulence, pigmentation, and biofilm formation. However, the regulatory network upon SigB in S. aureus is incompletely described. Here, we identified a novel substitution mutation, SigB(Q225P), which contributed the nonpigmented phenotype of S. aureus. The S. aureus mutant carrying SigB(Q225P) substitution lacks staphyloxanthin, a key virulence factor in protecting bacteria from host-oxidant killing, but retains bacterial pathogenicity with pleiotropic alterations in virulence factors, resulting in similar lethality and abscess formation ability in animal models. We also reported the SigB(Q225P) promotion of biofilm formation in S. aureus. Real-time quantitative polymerase chain reaction (RT-qPCR) revealed that the expression of nuc gene, which encodes thermonuclease, was significantly downregulated, resulting in accumulation of eDNA in the biofilm of SigB(Q225P) mutant strain. LacZ reporter assay showed that SigB(Q225P) influenced the activity of nuc promoter. Furthermore, electrophoretic mobility shift assay (EMSA) and Bio-layer interferometry (BLI) assay revealed that both SigB and SigB(Q225P) proteins could directly bind to nuc gene promoter; however, the binding activity decreased for SigB(Q225P). Our data renewed the understanding of the relationship between S. aureus golden pigment and its virulence and suggested that a single substitution mutation in SigB might enhance the biofilm formation of S. aureus by directly downregulating nuc expression.
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