Iron-Regulated Phospholipase C Activity Contributes to the Cytolytic Activity and Virulence of Acinetobacter baumannii.
Iron-Regulated Phospholipase C Activity Contributes to the Cytolytic Activity and Virulence of Acinetobacter baumannii.
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DOI：
10.1371/journal.pone.0167068
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Actis LA
中科院分区：
文献类型：
--
作者：
Fiester SE;Arivett BA;Schmidt RE;Beckett AC;Ticak T;Carrier MV;Ghosh R;Ohneck EJ;Metz ML;Sellin Jeffries MK;Actis LA
鲍曼不动杆菌是一种机会性革兰氏阴性病原体，可引起广泛的感染，包括肺炎、败血症、坏死性筋膜炎以及严重的伤口和尿路感染。分析A.在Chelex 100处理的培养基中生长的鲍曼不动杆菌代表性菌株的溶血活性表明，该病原体对绵羊、人和马红细胞的溶血性增加，有趣的是，这些红细胞在其膜中含有增加量的磷脂酰胆碱。对19株A.鲍曼不动杆菌分离株的基因组中含有两个磷脂酰胆碱特异性磷脂酶C（PC-PLC）基因，分别命名为plc 1和plc 2。因此，所有这些菌株均对马红细胞具有显著溶血性，并且其培养上清液检测为PC-PLC活性阳性。进一步分析表明，与富铁条件相比，在铁螯合条件下培养细菌时，plc 1和plc 2的转录表达以及磷脂酶的产生增加，从而溶血活性增加。对A.鲍曼不动杆菌ATCC 19606 T plc 1：：aph-FRT和plc 2：：aph同基因插入衍生物显示，与亲本菌株相比，这些突变体具有显著降低的PC-PLC活性，而plc 1：：ermAM/plc 2：：aph的测试表明，这种双重PC-PLC同基因突变体表达显著降低的细胞溶解和溶血活性。有趣的是，只有plc 1被证明对A有显著贡献。使用大蜡螟感染模型测定鲍曼不动杆菌毒力。总而言之，我们的数据表明，从共同祖先分化而来的PLC 1和PLC 2在溶血和溶细胞活性中发挥着协调一致的作用;尽管PLC 1似乎在A的毒力中发挥着更关键的作用。在无脊椎动物模型中测试时，这些活动将提供进入细胞内的铁储存，这种病原体可以在感染宿主的生长过程中使用。
Acinetobacter baumannii is an opportunistic Gram-negative pathogen that causes a wide range of infections including pneumonia, septicemia, necrotizing fasciitis and severe wound and urinary tract infections. Analysis of A. baumannii representative strains grown in Chelex 100-treated medium for hemolytic activity demonstrated that this pathogen is increasingly hemolytic to sheep, human and horse erythrocytes, which interestingly contain increasing amounts of phosphatidylcholine in their membranes. Bioinformatic, genetic and functional analyses of 19 A. baumannii isolates showed that the genomes of each strain contained two phosphatidylcholine-specific phospholipase C (PC-PLC) genes, which were named plc1 and plc2. Accordingly, all of these strains were significantly hemolytic to horse erythrocytes and their culture supernatants tested positive for PC-PLC activity. Further analyses showed that the transcriptional expression of plc1 and plc2 and the production of phospholipase and thus hemolytic activity increased when bacteria were cultured under iron-chelation as compared to iron-rich conditions. Testing of the A. baumannii ATCC 19606T plc1::aph-FRT and plc2::aph isogenic insertion derivatives showed that these mutants had a significantly reduced PC-PLC activity as compared to the parental strain, while testing of plc1::ermAM/plc2::aph demonstrated that this double PC-PLC isogenic mutant expressed significantly reduced cytolytic and hemolytic activity. Interestingly, only plc1 was shown to contribute significantly to A. baumannii virulence using the Galleria mellonella infection model. Taken together, our data demonstrate that both PLC1 and PLC2, which have diverged from a common ancestor, play a concerted role in hemolytic and cytolytic activities; although PLC1 seems to play a more critical role in the virulence of A. baumannii when tested in an invertebrate model. These activities would provide access to intracellular iron stores this pathogen could use during growth in the infected host.
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