Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection

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Title
Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection
Author(s)
D Lim; Su-Jin Park; H Y Kim; M Shin; M Song
Bibliographic Citation
Journal of Microbiology, vol. 60, no. 4, pp. 444-449
Publication Year
2022
Abstract
Available antibiotics to treat Acinetobacter baumannii infection is limited due to increasing resistance and the emergence of multiple drug-resistant strains. Hence, discovering effective agents against A. baumannii to reduce the number of infection-related deaths is imperative. In search of novel and alternative antibiotics, the antibacterial function of lipocalin2 (Lcn2) was investigated to treat systemic infections of A. baumannii using a mouse neutropenia model. We observed a significant increase in serum Lcn2 levels upon bacterial injection into the mouse, and the administration of recombinant Lcn2 (rmLcn2) extended their survival. Such protective effects were also observed in rmLcn2-pretreated macrophages, where rmLcn2 reduced the survival of the pathogen inside the macrophages. The underlying molecular mechanism of Lcn2 protection was also investigated. We observed that pretreatment of the Raw-264.7 macrophages with rmLcn2 markedly altered the expression of tonB3, which encodes a component of the transporter for ferrisiderophores in A. baumannii. However, the expression of katG, the gene encoding catalase, remained unaffected. These indicate that Lcn2-mediated defense against the pathogen is related to nutritional immunity rather than reactive oxygen species (ROS) production. Furthermore, the addition of rmLcn2 in infected mice diminished bacterial burden in multiple organs and enhanced the expression of tonB3 in the liver, spleen, and lungs of the infected mice. Increased survival rate due to rmLcn2 treatment declined when the infection model was established using lcn2-defective (lcn2-/-) mice, which indicated the necessity of endogenous Lcn2. Therefore, the antibacterial function of Lcn2 can be exploited to develop an alternative therapeutic agent against A. baumannii.
Keyword
Llipocalin2Acinetobacter baumanniiInfectionSepsis
ISSN
1225-8873
Publisher
Microbiological Society Korea
DOI
http://dx.doi.org/10.1007/s12275-022-2007-1
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
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