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驱动金黄色葡萄球菌可逆聚集的物理机制及对抗微生物药物的反应。

Physical mechanisms driving the reversible aggregation of Staphylococcus aureus and response to antimicrobials.

机构信息

Complex Assemblies of Soft Matter Laboratory (COMPASS), IRL 3254, CNRS-Solvay-University of Pennsylvania, CRTB, 350 George Patterson Boulevard, Bristol, PA, 19007, USA.

Solvay, Novecare CRTB, Bristol, PA, 19007, USA.

出版信息

Sci Rep. 2021 Jul 22;11(1):15048. doi: 10.1038/s41598-021-94457-1.

DOI:10.1038/s41598-021-94457-1
PMID:34294832
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8298462/
Abstract

Formation of non-sessile, auto-aggregated cells of Staphylococcus aureus contributes to surface colonization and biofilm formation, hence play a major role in the early establishment of infection and in tolerance to antimicrobials. Understanding the mechanism of aggregation and the impact of aggregation on the activity of antimicrobials is crucial in achieving a better control of this important pathogen. Previously linked to biological phenomena, physical interactions leading to S. aureus cellular aggregation and its protective features against antimicrobials remain unraveled. Herein, in-vitro experiments coupled with XDLVO simulations reveal that suspensions of S. aureus cells exhibit rapid, reversible aggregation (> 70%) in part controlled by the interplay between cellular hydrophobicity, surface potential and extracellular proteins. Changing pH and salt concentration in the extracellular media modulated the cellular surface potential but not the hydrophobicity which remained consistent despite these variations. A decrease in net cellular negative surface potential achieved by decreasing pH or increasing salt concentrations, caused attractive forces such as the hydrophobic and cell-protein interactions to prevail, favoring immediate aggregation. The aggregation significantly increased the tolerance of S. aureus cells to quaternary ammonium compounds (QAC). The well-dispersed cell population was completely inactivated within 30 s whereas its aggregated counterpart required more than 10 min.

摘要

金黄色葡萄球菌非附着、自动聚集细胞的形成有助于表面定植和生物膜形成,因此在感染的早期建立和对抗微生物药物的耐受性中起主要作用。了解聚集的机制以及聚集对抗微生物药物活性的影响对于更好地控制这种重要病原体至关重要。先前与生物学现象相关联的物理相互作用导致金黄色葡萄球菌细胞聚集及其对抗微生物药物的保护特性仍未被揭示。在此,体外实验与 XDLVO 模拟相结合表明,金黄色葡萄球菌细胞的悬浮液在部分受到细胞疏水性、表面电势和细胞外蛋白相互作用的控制下迅速、可逆地聚集(>70%)。改变细胞外介质的 pH 值和盐浓度调节细胞表面电势,但不调节疏水性,尽管存在这些变化,疏水性仍然保持一致。通过降低 pH 值或增加盐浓度来降低净细胞负表面电势,导致疏水性和细胞-蛋白质相互作用等吸引力占主导地位,有利于立即聚集。聚集显著增加了金黄色葡萄球菌细胞对季铵化合物(QAC)的耐受性。分散良好的细胞群体在 30 秒内完全失活,而其聚集的对应物则需要超过 10 分钟。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dae/8298462/8b4ecbb9cc95/41598_2021_94457_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dae/8298462/c36b7c0ab316/41598_2021_94457_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dae/8298462/eceba7a3faab/41598_2021_94457_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dae/8298462/8b4ecbb9cc95/41598_2021_94457_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dae/8298462/c36b7c0ab316/41598_2021_94457_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dae/8298462/eceba7a3faab/41598_2021_94457_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dae/8298462/8b4ecbb9cc95/41598_2021_94457_Fig3_HTML.jpg

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