Evolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa.
Evolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa.
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DOI：
10.1038/s41467-018-04996-x
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发表时间：
2018-07-06
影响因子：
16.6
通讯作者：
Neill DR
中科院分区：
文献类型：
--
作者：
Bricio-Moreno L;Sheridan VH;Goodhead I;Armstrong S;Wong JKL;Waters EM;Sarsby J;Panagiotou S;Dunn J;Chakraborty A;Fang Y;Griswold KE;Winstanley C;Fothergill JL;Kadioglu A;Neill DR
铜绿假单胞菌定植于囊性纤维化 (CF) 患者的上呼吸道，提供了宿主适应基因型的储存库，随后形成慢性肺部感染。我们之前在小鼠呼吸道感染模型中对铜绿假单胞菌进行了实验进化，并观察到 pmrB 的早期获得性突变，该突变编码促进感染建立和持续的双组分系统的传感器激酶。在这里，利用蛋白质组学，我们发现，相对于野生型菌株 LESB65，pmrB 突变体中参与 LPS 生物合成、抗菌素耐药性和吩嗪产生的蛋白质下调，而参与粘附、溶菌酶抗性和氯离子通道 CFTR 抑制的蛋白质上调。因此，pmrB 突变体对抗生素治疗敏感，但对气道上皮细胞的粘附性增强，对溶菌酶治疗具有抵抗力，并下调宿主 CFTR 表达。我们认为，CF 患者中的铜绿假单胞菌 pmrB 突变会经历进化权衡，导致定植潜力增强、CFTR 抑制和对宿主防御的抵抗力，但也会增加对抗生素的敏感性。从囊性纤维化患者体内分离出的铜绿假单胞菌中发现了 pmrB 基因突变。在这里，布里西奥-莫雷诺等人。在呼吸道感染的小鼠模型中表明，这些突变增强了细菌对上皮细胞的粘附和对溶菌酶的抵抗力，但也增加了抗生素的敏感性。
Pseudomonas aeruginosa colonises the upper airway of cystic fibrosis (CF) patients, providing a reservoir of host-adapted genotypes that subsequently establish chronic lung infection. We previously experimentally-evolved P. aeruginosa in a murine model of respiratory tract infection and observed early-acquired mutations in pmrB, encoding the sensor kinase of a two-component system that promoted establishment and persistence of infection. Here, using proteomics, we show downregulation of proteins involved in LPS biosynthesis, antimicrobial resistance and phenazine production in pmrB mutants, and upregulation of proteins involved in adherence, lysozyme resistance and inhibition of the chloride ion channel CFTR, relative to wild-type strain LESB65. Accordingly, pmrB mutants are susceptible to antibiotic treatment but show enhanced adherence to airway epithelial cells, resistance to lysozyme treatment, and downregulate host CFTR expression. We propose that P. aeruginosa pmrB mutations in CF patients are subject to an evolutionary trade-off, leading to enhanced colonisation potential, CFTR inhibition, and resistance to host defences, but also to increased susceptibility to antibiotics. Mutations in gene pmrB are found in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Here, Bricio-Moreno et al. show in a mouse model of respiratory infection that the mutations enhance bacterial adherence to epithelial cells and resistance to lysozyme, but also increase antibiotic susceptibility.
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影响因子：
2.8
作者：
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通讯作者：
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影响因子：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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