Elucidating the Pseudomonas aeruginosa fatty acid degradation pathway: identification of additional fatty acyl-CoA synthetase homologues.

Elucidating the Pseudomonas aeruginosa fatty acid degradation pathway: identification of additional fatty acyl-CoA synthetase homologues.
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DOI:
10.1371/journal.pone.0064554
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Hoang TT
Hoang TT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zarzycki-Siek J;Norris MH;Kang Y;Sun Z;Bluhm AP;McMillan IA;Hoang TT

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最近研究发现,条件致病菌铜绿假单胞菌(Pseudomonas aeruginosa)的脂肪酸降解途径参与了BALB/c小鼠肺部感染模型的营养获取。肺内FA的来源被认为是磷脂酰胆碱,它是肺表面活性剂的主要成分。先前的研究表明,P. aeruginosa有两个以上的脂肪酰基辅酶a合成酶基因(fadD; PA3299和PA3300),它们负责利用ATP和辅酶a激活FAs。通过生物信息学方法,本研究通过与大肠杆菌fadD同源性鉴定了11个候选基因。四个新的fadD同源物(PA1617、PA2893、PA3860和PA3924)在功能上被证实能够在含fa的培养基上补充大肠杆菌fadD突变体。17个fadD组合突变体在不同FA上作为唯一碳源的生长表型表明,4个新的fadD同源物参与FA降解,使铜绿假单胞菌fadD基因总数达到6个。在4个新的同源物中,fadD4 (PA1617)对不同链长FAs的降解作用最大。fadD4突变体以香茅醛和天竺葵酸为唯一碳源和能量来源的植物性香料物质的生长模式表明,fadD4也参与了这些植物性化合物的降解。与ΔfadD1D2突变体相比,六联体fadD突变体的适应度下降仅在BALB/c小鼠肺部感染24 h时观察到。
The fatty acid (FA) degradation pathway of Pseudomonas aeruginosa, an opportunistic pathogen, was recently shown to be involved in nutrient acquisition during BALB/c mouse lung infection model. The source of FA in the lung is believed to be phosphatidylcholine, the major component of lung surfactant. Previous research indicated that P. aeruginosa has more than two fatty acyl-CoA synthetase genes (fadD; PA3299 and PA3300), which are responsible for activation of FAs using ATP and coenzyme A. Through a bioinformatics approach, 11 candidate genes were identified by their homology to the Escherichia coli FadD in the present study. Four new homologues of fadD (PA1617, PA2893, PA3860, and PA3924) were functionally confirmed by their ability to complement the E. coli fadD mutant on FA-containing media. Growth phenotypes of 17 combinatorial fadD mutants on different FAs, as sole carbon sources, indicated that the four new fadD homologues are involved in FA degradation, bringing the total number of P. aeruginosa fadD genes to six. Of the four new homologues, fadD4 (PA1617) contributed the most to the degradation of different chain length FAs. Growth patterns of various fadD mutants on plant-based perfumery substances, citronellic and geranic acids, as sole carbon and energy sources indicated that fadD4 is also involved in the degradation of these plant-derived compounds. A decrease in fitness of the sextuple fadD mutant, relative to the ΔfadD1D2 mutant, was only observed during BALB/c mouse lung infection at 24 h.
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