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In vivo Fitness of Acinetobacter baumannii Strains in Murine Infection Is Associated with International Lineage II-rep-2 and International Lineage III Clones Showing High Case Fatality Rates in Human Infections.
Microorganisms ( IF 4.1 ) Pub Date : 2020-06-04 , DOI: 10.3390/microorganisms8060847
Amir Nutman 1, 2 , Jonathan Lellouche 1 , Ziv Lifshitz 1 , Rivka Glick 1 , Yehuda Carmeli 1, 2
Affiliation  

We previously reported that the 14-day case fatality rate (CFR) in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia varied between infecting clones. Here, we evaluated the in vitro and in vivo fitness of CRAB blood isolates belonging to clones with low CFR (< 32% 14-day mortality) and high CFR (65% 14-day mortality). Fitness was measured in vitro using a growth curve assay and in vivo using murine thigh muscle and septicemia models of infection. Our sample included 38 CRAB isolates belonging to two clones with low CFR (international lineage (IL)-II-rep-1, n = 13 and IL-79, n = 6) and two clones with high CFR (IL-III, n = 9 and IL-II-rep-2, n = 10). In in vitro growth curves, mean lag time, generation time and maximal growth varied between clones but could not discriminate between the high and low CFR clones. In the in vivo models, bacterial burdens were higher in mice infected with high CFR clones than in those infected with low CFR clones: in thigh muscle, 8.78 ± 0.25 vs. 7.53 ± 0.25 log10CFU/g, p < 0.001; in infected spleen, 5.53 ± 0.38 vs. 3.71 ± 0.35 log10CFU/g, p < 0.001. The thigh muscle and septicemia model results were closely correlated (r = 0.93, p < 0.01). These results suggest that in vivo but not in vitro fitness is associated with high CFR clones.

中文翻译:

鲍曼不动杆菌菌株在小鼠感染中的体内适应性与国际谱系II-rep-2和国际谱系III克隆在人类感染中显示高病死率相关。

我们先前曾报道对碳青霉烯耐药的鲍曼不动杆菌患者的14天病死率(CFR)(CRAB)菌血症在感染克隆之间有所不同。在这里,我们评估了属于低CFR(<32%14天死亡率)和高CFR(65%14天死亡率)克隆的CRAB血液分离株的体外和体内适应性。使用生长曲线测定法在体外测量健身度,使用鼠大腿肌肉和感染的败血病模型在体内测量健身度。我们的样本包括38个CRAB分离株,它们分别属于两个CFR低的克隆(国际谱系(IL)-II-rep-1,n = 13和IL-79,n = 6)和两个CFR高的克隆(IL-III,n = 9,IL-II-rep-2,n = 10)。在体外生长曲线中,克隆之间的平均滞后时间,生成时间和最大生长有所不同,但无法区分高和低CFR克隆。在体内模型中,感染高CFR克隆的小鼠的细菌负担高于感染低CFR克隆的小鼠:10 CFU / g,p <0.001;感染的脾脏中,5.53±0.38 vs.3.71±0.35 log 10 CFU / g,p <0.001。大腿肌肉和败血病模型的结果密切相关(r = 0.93,p <0.01)。这些结果表明体内但非体外的适应性与高CFR克隆有关。
更新日期:2020-06-04
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