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LcpB是一种焦磷酸酶,负责临床分离株ST59中壁磷壁酸的合成和毒力。

LcpB Is a Pyrophosphatase Responsible for Wall Teichoic Acid Synthesis and Virulence in Clinical Isolate ST59.

作者信息

Pan Ting, Guan Jing, Li Yujie, Sun Baolin

机构信息

Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Front Microbiol. 2021 Dec 16;12:788500. doi: 10.3389/fmicb.2021.788500. eCollection 2021.

DOI:10.3389/fmicb.2021.788500
PMID:34975809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8716876/
Abstract

The community-associated methicillin-resistant (CA-MRSA) causes severe pandemics primarily consisting of skin and soft tissue infections. However, the underlying pathomechanisms of the bacterium are yet to fully understood. The present study identifies LcpB protein, which belongs to the LytR-A-Psr (LCP) family, is crucial for cell wall synthesis and virulence in . The findings revealed that LcpB is a pyrophosphatase responsible for wall teichoic acid synthesis. The results also showed that LcpB regulates enzyme activity through specific key arginine sites in its LCP domain. Furthermore, knockout of in the CA-MRSA isolate ST59 resulted in enhanced hemolytic activity, enlarged of abscesses, and increased leukocyte infiltration. Meanwhile, we also found that LcpB regulates virulence in -independent manner and the key sites for pyrophosphatase of LcpB play critical roles in regulating the virulence. In addition, the results showed that the role of LcpB was different between methicillin-resistant (MRSA) and methicillin-sensitive (MSSA). This study therefore highlights the dual role of LcpB in cell wall synthesis and regulation of virulence. These insights on the underlying molecular mechanisms can thus guide the development of novel anti-infective strategies.

摘要

社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)引发主要由皮肤和软组织感染构成的严重大流行。然而,该细菌的潜在致病机制尚未完全明确。本研究鉴定出属于LytR-A-Psr(LCP)家族的LcpB蛋白,其对于[具体菌名未明确,此处原文缺失]的细胞壁合成和毒力至关重要。研究结果表明,LcpB是一种负责壁磷壁酸合成的焦磷酸酶。结果还显示,LcpB通过其LCP结构域中的特定关键精氨酸位点调节酶活性。此外,在CA-MRSA分离株ST59中敲除[具体基因未明确,此处原文缺失]导致溶血活性增强、脓肿增大以及白细胞浸润增加。同时,我们还发现LcpB以不依赖[具体因素未明确,此处原文缺失]的方式调节毒力,且LcpB焦磷酸酶的关键位点在调节毒力中起关键作用。此外,结果表明LcpB在耐甲氧西林金黄色葡萄球菌(MRSA)和甲氧西林敏感金黄色葡萄球菌(MSSA)中的作用有所不同。因此,本研究突出了LcpB在细胞壁合成和毒力调节中的双重作用。这些关于潜在分子机制的见解因而能够指导新型抗感染策略的开发。

相似文献

1
LcpB Is a Pyrophosphatase Responsible for Wall Teichoic Acid Synthesis and Virulence in Clinical Isolate ST59.LcpB是一种焦磷酸酶,负责临床分离株ST59中壁磷壁酸的合成和毒力。
Front Microbiol. 2021 Dec 16;12:788500. doi: 10.3389/fmicb.2021.788500. eCollection 2021.
2
Corrigendum: LcpB is a pyrophosphatase responsible for wall teichoic acid synthesis and virulence in clinical isolate ST59.勘误:LcpB是一种焦磷酸酶,负责临床分离株ST59中壁磷壁酸的合成和毒力。
Front Microbiol. 2023 Jul 4;14:1229396. doi: 10.3389/fmicb.2023.1229396. eCollection 2023.
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Impairment of the Cell Wall Ligase, LytR-CpsA-Psr Protein (LcpC), in Methicillin Resistant Reduces Its Resistance to Antibiotics and Infection in a Mouse Model of Sepsis.细胞壁连接酶LytR-CpsA-Psr蛋白(LcpC)功能受损会降低耐甲氧西林菌在脓毒症小鼠模型中的抗生素耐药性及感染能力。
Front Microbiol. 2020 Apr 16;11:557. doi: 10.3389/fmicb.2020.00557. eCollection 2020.
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Wall teichoic acids mediate increased virulence in Staphylococcus aureus.细胞壁磷壁酸可介导金黄色葡萄球菌毒力增强。
Nat Microbiol. 2017 Jan 23;2:16257. doi: 10.1038/nmicrobiol.2016.257.
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Virulence determinants associated with the Asian community-associated methicillin-resistant Staphylococcus aureus lineage ST59.与亚洲社区相关的耐甲氧西林金黄色葡萄球菌 ST59 谱系相关的毒力决定因素。
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Molecular characteristics of community-acquired methicillin-resistant Staphylococcus aureus strains isolated from outpatients with skin and soft tissue infections in Wuhan, China.从中国武汉门诊皮肤及软组织感染患者中分离出的社区获得性耐甲氧西林金黄色葡萄球菌菌株的分子特征
Pathog Dis. 2016 Jun;74(4):ftw026. doi: 10.1093/femspd/ftw026. Epub 2016 Apr 7.
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Epidemiology and molecular characteristics of community-associated methicillin-resistant and methicillin-susceptible Staphylococcus aureus from skin/soft tissue infections in a children's hospital in Beijing, China.中国北京一家儿童医院皮肤/软组织感染中社区相关性耐甲氧西林金黄色葡萄球菌和甲氧西林敏感金黄色葡萄球菌的流行病学和分子特征。
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Antibiotic susceptibility and genomic variations in Staphylococcus aureus associated with Skin and Soft Tissue Infection (SSTI) disease groups.与皮肤和软组织感染(SSTI)疾病组相关的金黄色葡萄球菌的抗生素敏感性和基因组变异
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Accessory gene regulator (agr) dysfunction was unusual in Staphylococcus aureus isolated from Chinese children.在中国儿童分离的金黄色葡萄球菌中, accessory gene regulator (agr) 功能障碍不常见。
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Front Microbiol. 2022 Oct 17;13:1008052. doi: 10.3389/fmicb.2022.1008052. eCollection 2022.

本文引用的文献

1
Modification of cell wall polysaccharide guides cell division in Streptococcus mutans.细胞壁多糖的修饰指导变形链球菌的细胞分裂。
Nat Chem Biol. 2021 Aug;17(8):878-887. doi: 10.1038/s41589-021-00803-9. Epub 2021 May 27.
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VraCP regulates cell wall metabolism and antibiotic resistance in vancomycin-intermediate Staphylococcus aureus strain Mu50.VraCP调节万古霉素中介金黄色葡萄球菌菌株Mu50中的细胞壁代谢和抗生素抗性。
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Wall Teichoic Acid in Staphylococcus aureus Host Interaction.
金黄色葡萄球菌宿主相互作用中的壁磷壁酸。
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Impairment of the Cell Wall Ligase, LytR-CpsA-Psr Protein (LcpC), in Methicillin Resistant Reduces Its Resistance to Antibiotics and Infection in a Mouse Model of Sepsis.细胞壁连接酶LytR-CpsA-Psr蛋白(LcpC)功能受损会降低耐甲氧西林菌在脓毒症小鼠模型中的抗生素耐药性及感染能力。
Front Microbiol. 2020 Apr 16;11:557. doi: 10.3389/fmicb.2020.00557. eCollection 2020.
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Crystallographic analysis of LcpA, the primary wall teichoic acid ligase.LcpA 的晶体结构分析,一种主要细胞壁磷壁酸连接酶。
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The Staphylococcal Cell Wall.葡萄球菌细胞壁。
Microbiol Spectr. 2019 Jul;7(4). doi: 10.1128/microbiolspec.GPP3-0068-2019.
7
Structure and Mechanism of LcpA, a Phosphotransferase That Mediates Glycosylation of a Gram-Positive Bacterial Cell Wall-Anchored Protein.LcpA 的结构与机制:一种磷酸转移酶,介导革兰氏阳性菌细胞壁锚定蛋白的糖基化。
mBio. 2019 Feb 19;10(1):e01580-18. doi: 10.1128/mBio.01580-18.
8
Peptidoglycan Cross-Linking Preferences of Staphylococcus aureus Penicillin-Binding Proteins Have Implications for Treating MRSA Infections.金黄色葡萄球菌青霉素结合蛋白对肽聚糖交联的偏好影响治疗耐甲氧西林金黄色葡萄球菌感染的效果。
J Am Chem Soc. 2017 Jul 26;139(29):9791-9794. doi: 10.1021/jacs.7b04881. Epub 2017 Jul 11.
9
In vitro reconstitution demonstrates the cell wall ligase activity of LCP proteins.体外重组实验证明了LCP蛋白的细胞壁连接酶活性。
Nat Chem Biol. 2017 Apr;13(4):396-401. doi: 10.1038/nchembio.2302. Epub 2017 Feb 6.
10
Wall teichoic acids mediate increased virulence in Staphylococcus aureus.细胞壁磷壁酸可介导金黄色葡萄球菌毒力增强。
Nat Microbiol. 2017 Jan 23;2:16257. doi: 10.1038/nmicrobiol.2016.257.