Dogan Ozlem, Vatansever Cansel, Atac Nazli, Albayrak Ozgur, Karahuseyinoglu Sercin, Sahin Ozgun Ekin, Kilicoglu Bilge Kaan, Demiray Atalay, Ergonul Onder, Gönen Mehmet, Can Fusun
Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Koc University, Istanbul 34450, Turkey.
Department of Histology and Embryology, School of Medicine, Koc University, Istanbul 34450, Turkey.
Biology (Basel). 2021 May 14;10(5):436. doi: 10.3390/biology10050436.
We proposed the hypothesis that high-risk clones of colistin-resistant (ColR-Kp) possesses a high number of virulence factors and has enhanced survival capacity against the neutrophil activity. We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive ColR-Kp infections. The ST101 and ST395 ColR-Kp infections had higher 30-day mortality (58%, = 0.005 and 75%, = 0.003). The presence of yersiniabactin biosynthesis gene () and ferric uptake operon associated gene () were significantly higher in ST101 (99%, ≤ 0.001) and ST395 (94%, < 0.012). Being in ICU (OR: 7.9; CI: 1.43-55.98; = 0.024), (OR:27.0; CI: 5.67-179.65; < 0.001) and ST101 (OR: 17.2; CI: 2.45-350.40; = 0.01) were found to be predictors of 30-day mortality. Even the neutrophil uptake of +-+ ColR-Kp was significantly higher than --- ColR-Kp (phagocytosis rate: 78% vs. 65%, < 0.001), and the +-+ ColR-Kp survived more than --- ColR-Kp (median survival index: 7.90 vs. 4.22; = 0.001). The +-+ ColR-Kp stimulated excessive NET formation. Iron uptake systems in high-risk clones of colistin-resistant enhance the success of survival against the neutrophil phagocytic defense and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for the treatment of colistin-resistant high-risk clones of infections.
我们提出了一个假设，即耐黏菌素（ColR-Kp）的高风险克隆具有大量毒力因子，并且对中性粒细胞活性具有更强的生存能力。我们研究了142例侵袭性ColR-Kp感染患者中ColR-Kp分离株的毒力基因和中性粒细胞反应。ST101和ST395 ColR-Kp感染的30天死亡率更高（分别为58%，P = 0.005和75%，P = 0.003）。yersiniabactin生物合成基因（ybt）和铁摄取操纵子相关基因（iro）在ST101（99%，P≤0.001）和ST395（94%，P<0.012）中的存在显著更高。入住ICU（比值比：7.9；可信区间：1.43 - 55.98；P = 0.024）、ybt（比值比：27.0；可信区间：5.67 - 179.65；P<0.001）和ST101（比值比：17.2；可信区间：2.45 - 350.40；P = 0.01）被发现是30天死亡率的预测因素。甚至+-+ ColR-Kp的中性粒细胞摄取显著高于--- ColR-Kp（吞噬率：78%对65%，P<0.001）,并且+-+ ColR-Kp比--- ColR-Kp存活时间更长（中位生存指数：7.90对4.22；P = 0.001）。+-+ ColR-Kp刺激了过量的中性粒细胞胞外陷阱形成。耐黏菌素的高风险克隆中的铁摄取系统增强了抵抗中性粒细胞吞噬防御的生存成功率，并刺激了过量的中性粒细胞胞外陷阱形成。针对铁摄取系统的药物将是治疗耐黏菌素高风险克隆感染的一种有前景的方法。
