Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system

Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system
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DOI:
10.1128/jb.184.11.3027-3033.2002
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发表时间:
2002-06-01
影响因子:
3.2
通讯作者:
Köhler, T
Köhler, T
中科院分区:
生物学3区
文献类型:
--
作者:
Cosson, P;Zulianello, L;Köhler, T

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铜绿假单胞菌是一种重要的条件致病菌,可产生多种细胞相关和分泌的毒力因子。铜绿假单胞菌感染很难有效治疗,因为快速出现耐药菌株。在本研究中,我们分析了是否可以使用盘状双囊变形虫作为一个简单的模型系统来分析铜绿假单胞菌菌株的毒力。野生型菌株PAO 1对D.盘状突。在las quorum感应系统中缺陷的同基因突变体几乎与野生型一样具有抑制作用,而rhl quorum感应突变体允许网骨藻细胞的生长。因此,在这个模型系统中,由rhl群体感应系统控制的因素被发现起着核心作用。其中,野生型菌株PAO 1分泌的鼠李糖脂能诱导D.盘状突细胞通过使用这个简单的模型系统,我们预测铜绿假单胞菌的某些耐药突变体应该显示出降低的毒力。这一结果在急性肺炎大鼠模型中得到证实。因此,D.盘状假单胞菌可以作为一个简单的非哺乳动物宿主系统来评估铜绿假单胞菌的致病性。
Pseudomonas aeruginosa is an important opportunistic pathogen that produces a variety of cell-associated and secreted virulence factors. P. aeruginosa infections are difficult to treat effectively because of the rapid emergence of antibiotic-resistant strains. In this study, we analyzed whether the amoeba Dicityostelium discoideum can be used as a simple model system to analyze the virulence of P. aeruginosa strains. The virulent wild-type strain PAO1 was shown to inhibit growth of D. discoideum. Isogenic mutants deficient in the las quorum-sensing system were almost as inhibitory as the wild type, while rhl quorum-sensing mutants permitted growth of Dictyostelium cells. Therefore, in this model system, factors controlled by the rhl quorum-sensing system were found to play a central role. Among these, rhamnolipids secreted by the wild-type strain PAO1 could induce fast lysis of D. discoideum cells. By using this simple model system, we predicted that certain antibiotic-resistant mutants of P. aeruginosa should show reduced virulence. This result was confirmed in a rat model of acute pneumonia. Thus, D. discoideum could be used as a simple nonmammalian host system to assess pathogenicity of P. aeruginosa.