Absence of Protoheme IX Farnesyltransferase CtaB Causes Virulence Attenuation but Enhances Pigment Production and Persister Survival in MRSA.

Absence of Protoheme IX Farnesyltransferase CtaB Causes Virulence Attenuation but Enhances Pigment Production and Persister Survival in MRSA.
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原血红素 IX 法呢基转移酶 CtaB 的缺失会导致 MRSA 毒力减弱,但会增强色素产生并保持存活

DOI:
10.3389/fmicb.2016.01625
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发表时间:
2016
影响因子:
5.2
通讯作者:
Zhang Y
Zhang Y
中科院分区:
生物学2区
文献类型:
--
作者:
Xu T;Han J;Zhang J;Chen J;Wu N;Zhang W;Zhang Y

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金黄色葡萄球菌的膜蛋白CtaB是一种原血红素IX法尼基转移酶,参与细菌呼吸链中含血红素末端氧化酶的合成。在本研究中,为了评估CtaB在金黄色葡萄球菌毒力、色素生成和持久性形成中的作用,我们在耐甲氧西林金黄色葡萄球菌(MRSA)菌株USA500中构建了CtaB突变体。我们发现ctaB的缺失减弱了小鼠的生长和毒力,但增强了固定期喹诺酮耐受性持久细胞的色素生成和形成。RNA-seq分析显示,ctaB的缺失导致包括RNAIII在内的多个毒力基因转录减少,这与ctaB的毒力衰减一致。此外,与亲本相比,ctaB敲除突变体中20个核糖体基因和24个氨基酸生物合成相关基因的转录显著下调。这些发现表明血红素生物合成在金黄色葡萄球菌的毒力和持久性形成中的重要性。
The membrane protein CtaB in S. aureus is a protoheme IX farnesyltransferase involved in the synthesis of the heme containing terminal oxidases of bacterial respiratory chain. In this study, to assess the role of CtaB in S. aureus virulence, pigment production, and persister formation, we constructed a ctaB mutant in the methicillin-resistant Staphylococcus aureus (MRSA) strain USA500. We found that deletion of ctaB attenuated growth and virulence in mice but enhanced pigment production and formation of quinolone tolerant persister cells in stationary phase. RNA-seq analysis showed that deletion of ctaB caused decreased transcription of several virulence genes including RNAIII which is consistent with its virulence attenuation. In addition, transcription of 20 ribosomal genes and 24 genes involved in amino acid biosynthesis was significantly down-regulated in the ctaB knockout mutant compared with the parent strain. These findings suggest the importance of heme biosynthesis in virulence and persister formation of S. aureus.
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