当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES期刊下所有文献 > Proteomic analysis of iron-regulated membrane proteins identify FhuE receptor as a target to inhibit siderophore-mediated iron acquisition in Acinetobacter baumannii.

Proteomic analysis of iron-regulated membrane proteins identify FhuE receptor as a target to inhibit siderophore-mediated iron acquisition in Acinetobacter baumannii.

Abstract：

:Survival of the Acinetobacter baumannii inside host requires different micronutrients such as iron, but their bioavailability is limited because of nutritional immunity created by host. A. baumannii has to develop mechanisms to acquire nutrient iron during infection. The present study is an attempt to identify membrane proteins involved in iron sequestration mechanism of A. baumannii using two-dimensional electrophoresis and LC-MS/MS analysis. The identified iron-regulated membrane protein (IRMP) of A. baumannii was used for its interaction studies with different siderophores, and designing of the inhibitor against A. baumannii targeting this IRMP. Membrane proteomic results identified over-expression of four membrane proteins (Fhu-E receptor, ferric-acinetobactin receptor, ferrienterochelin receptor, and ferric siderophore receptor) under iron-limited condition. A. baumannii produces siderophores that have good interaction with the FhuE receptor. Result also showed that FhuE receptor has interaction with siderophores produced by other bacteria. Interaction of FhuE receptor and siderophores helps in iron sequestration and survival of Acinetobacter under nutritional immunity imposed by the host. Hence it becomes essential to find a potential inhibitor for the FhuE receptor that can inhibit the survival of A. baumannii in the host. In-silico screening, and molecular mechanics studies identified ZINC03794794 and ZINC01530652 as a likely lead to design inhibitor against the FhuE receptor of A. baumannii. The designed inhibitor is experimentally validated for its antibacterial activity on the A. baumannii. Therefore, designed inhibitor interferes with the iron acquisition mechanism of Acinetobacter hence may prove useful for preventing infection caused by A. baumannii by limiting nutrient availability.

journal_name

Int J Biol Macromol

journal_title

International journal of biological macromolecules

authors

Tiwari V,Rajeswari MR,Tiwari M

doi

10.1016/j.ijbiomac.2018.12.173

subject

Has Abstract

pub_date

2019-03-15 00:00:00

pages

1156-1167

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(18)35059-1

journal_volume

125

pub_type

杂志文章

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