College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA.
Toxins (Basel). 2021 Oct 14;13(10):726. doi: 10.3390/toxins13100726.
Alpha toxin (Hla) is a major virulence factor of that targets platelets but clinical data on Hla pathogenesis in bacteremia (SAB) is limited. We examined the link between in vitro Hla activity and outcome. Study isolates obtained from 100 patients with SAB (50 survivors; 50 non-survivors) were assessed for in vitro Hla production by Western immunoblotting in a subset of isolates and Hla activity by hemolysis assay in all isolates. Relevant demographics, laboratory and clinical data were extracted from patients' medical records to correlate Hla activity of the infecting isolates with outcome. Hla production strongly correlated with hemolytic activity ( = 0.93) in vitro. A trend towards higher hemolytic activity was observed for MRSA compared to MSSA and with high-risk source infection. Significantly higher hemolytic activity was noted for MRSA strains isolated from patients who developed thrombocytopenia (median 52.48 vs. 16.55 HU/mL in normal platelet count, = 0.012) and from non survivors (median 30.96 vs. 14.87 HU/mL in survivors, = 0.014) but hemolytic activity of MSSA strains did not differ between patient groups. In vitro Hla activity of strains obtained from patients with bacteremia is significantly associated with increased risk for thrombocytopenia and death which supports future studies to evaluate feasibility of bedside phenotyping and therapeutic targeting.
α 毒素（Hla）是 的主要毒力因子，靶向血小板，但有关菌血症（SAB）中 Hla 发病机制的临床数据有限。我们研究了体外 Hla 活性与结局之间的关系。从 100 例 SAB 患者（50 例幸存者；50 例非幸存者）中获得的研究分离株，通过 Western 免疫印迹法在部分分离株中评估体外 Hla 产生情况，并通过溶血试验在所有分离株中评估 Hla 活性。从患者的病历中提取相关人口统计学、实验室和临床数据，将感染分离株的 Hla 活性与结局相关联。Hla 的产生与体外溶血活性呈强相关性（ = 0.93）。与 MSSA 相比，MRSA 的溶血活性呈升高趋势，高危源感染也是如此。从发生血小板减少症的患者中分离出的 MRSA 菌株（中位 52.48 vs. 正常血小板计数时的 16.55 HU/mL， = 0.012）和非幸存者（中位 30.96 vs. 幸存者时的 14.87 HU/mL， = 0.014）的溶血活性明显更高，而 MSSA 菌株的溶血活性在患者组之间没有差异。从菌血症患者中获得的 菌株的体外 Hla 活性与血小板减少症和死亡风险增加显著相关，这支持未来评估床边表型和治疗靶向可行性的研究。
