Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) Genetic Factors Involved in Human Endothelial Cells Damage, an Important Phenotype Correlated with Persistent Endovascular Infection.
Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) Genetic Factors Involved in Human Endothelial Cells Damage, an Important Phenotype Correlated with Persistent Endovascular Infection.
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DOI：
10.3390/antibiotics11030316
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发表时间：
2022-02-26
期刊：
影响因子：
--
通讯作者：
Xiong YQ
中科院分区：
文献类型：
--
作者：
Xiao X;Li Y;Li L;Xiong YQ
耐甲氧西林金黄色葡萄球菌（MRSA）是危及生命的血管内感染的主要原因。内皮细胞（EC）损伤是这些综合征发病机制中的关键因素。然而，与EC损伤相关的遗传因素尚未得到很好的研究。本研究旨在通过筛选全基因组内布拉斯加转座子突变库（NTML），确定影响人类EC损伤的遗传决定因素。采用MTT法检测NTML中各突变株对人EC细胞系HMEC-1的体外损伤作用。我们首先确认了一些全球调节因子和基因对EC损伤有积极影响，这与已发表的结果一致。这些数据支持高通量方法的实用性。重要的是，我们证明了317个突变体显著降低了EC损伤，而只有6个突变体与亲本JE 2菌株相比增强了EC损伤。这些基因中的大多数以前没有被定义为影响人类EC损伤。有趣的是，这些新发现的基因中有许多涉及代谢、遗传和环境信息处理以及细胞过程。这些结果推进了我们对与人类EC损伤相关的葡萄球菌遗传因子的认识，这可能为开发抗MRSA血管内感染的有效药物提供新的靶点。
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of life-threatening endovascular infections. Endothelial cell (EC) damage is a key factor in the pathogenesis of these syndromes. However, genetic factors related to the EC damage have not been well studied. This study aims to identify genetic determinants that impact human EC damage by screening the genome-wide Nebraska Transposon Mutant Library (NTML). A well-established MTT assay was used to test the in vitro damage of human EC cell line (HMEC-1) caused by each mutant strain in the NTML. We first confirmed some global regulators and genes positively impact the EC damage, which is consistent with published results. These data support the utility of the high-throughput approach. Importantly, we demonstrated 317 mutants significantly decreased the EC damage, while only 6 mutants enhanced the EC damage vs. parental JE2 strain. The majority of these genes have not been previously defined to affect human EC damage. Interestingly, many of these newly identified genes are involved in metabolism, genetic and environmental information processing, and cellular processes. These results advance our knowledge of staphylococcal genetic factors related to human EC damage which may provide novel targets for the development of effective agents against MRSA endovascular infection.
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琥珀酰辅酶A的积累使甲氧西林抗葡萄球菌金黄色葡萄球菌（MRSA）琥珀酰基琥珀酰基琥珀酰基琥珀酰基琥珀酰基琥珀酸酯菌，与β-内酰胺抗生素的易感性增加有关。
影响因子：
6.4
作者：
Campbell C;Fingleton C;Zeden MS;Bueno E;Gallagher LA;Shinde D;Ahn J;Olson HM;Fillmore TL;Adkins JN;Razvi F;Bayles KW;Fey PD;Thomas VC;Cava F;Clair GC;O'Gara JP
通讯作者：
O'Gara JP
影响因子：
3.7
作者：
Quiblier C;Seidl K;Roschitzki B;Zinkernagel AS;Berger-Bächi B;Senn MM
通讯作者：
Senn MM
影响因子：
5.8
作者：
Ferrero, Mariana C.;Bregante, Julieta;Baldi, Pablo C.
通讯作者：
Baldi, Pablo C.
影响因子：
3.1
作者：
Atwood, Danielle N.;Beenken, Karen E.;Smeltzer, Mark S.
通讯作者：
Smeltzer, Mark S.
影响因子：
6.4
作者：
Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW