Balaska Asimina, Polonyfi Katerina, Rigatou Anastasia, Miliotis Georgios, Margaroni Maritsa, Daikos George L, Drogari-Apiranthitou Maria
Hellenic National Public Health Organization (EODY), Athens, Greece.
First Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Access Microbiol. 2021 Nov 2;3(11):000275. doi: 10.1099/acmi.0.000275. eCollection 2021.
-carbapenemase-producing (KPC) sequence-type 258 (ST258) has emerged as an important human pathogen throughout the world. Although lacking known virulence factors, it is associated with significant morbidity and high mortality rates. The pathogenicity of KPC ST258 strains has not been fully elucidated yet. We sought to investigate the interactions of the KPC ST258-clade I with different components of innate immunity. Human serum was used to evaluate the serum bactericidal activity and the J774A.1 murine (BALB/c mice) macrophage cell-line was used to examine phagocytosis, mRNA expression and production of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. L-78, a KPC-producing ST258-clade I strain was used as representative of the strains circulating in Greek hospitals. ATCC 43816, a virulent K2 strain, was used for comparison. Strain L-78 was susceptible to human serum and rapidly phagocytosed by J774A.1 cells, in contrast to the virulent K2 strain, which was serum-resistant and slowly phagocytosed. Stimulation of the J774A.1 cells with the L-78 strain induced production of IL-1β at concentration levels significantly higher compared to K2, whereas production of TNF-α and IL-6 levels were comparable by the two strains. L-78 was able to induce IL-1β mRNA and NLRP3 mRNA expression. Our findings indicate that ST258-clade I is serum sensitive, rapidly phagocytosed and is capable of eliciting adequate innate immune response in terms of production of pro-inflammatory cytokines.
产碳青霉烯酶（KPC）的序列型258（ST258）已成为全球一种重要的人类病原体。尽管缺乏已知的毒力因子，但它与显著的发病率和高死亡率相关。KPC ST258菌株的致病性尚未完全阐明。我们试图研究KPC ST258进化枝I与天然免疫不同成分之间的相互作用。使用人血清评估血清杀菌活性，并使用J774A.1小鼠（BALB/c小鼠）巨噬细胞系检测吞噬作用、mRNA表达以及促炎细胞因子IL-1β、TNF-α和IL-6的产生。产KPC的ST258进化枝I菌株L-78被用作希腊医院中流行菌株的代表。毒力K2菌株ATCC 43816用于比较。与血清耐药且吞噬缓慢的毒力K2菌株相比，菌株L-78对人血清敏感，并被J774A.1细胞快速吞噬。用L-78菌株刺激J774A.1细胞诱导产生的IL-1β浓度水平显著高于K2菌株，而TNF-α和IL-6的产生水平在两种菌株中相当。L-78能够诱导IL-1β mRNA和NLRP3 mRNA表达。我们的研究结果表明，ST258进化枝I对血清敏感，能被快速吞噬，并且在促炎细胞因子产生方面能够引发充分的天然免疫反应。
