- Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection
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Daejin Lim , Su-Jin Park , Ha Young Kim , Minsang Shin , Miryoung Song
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J. Microbiol. 2022;60(4):444-449. Published online March 28, 2022
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DOI: https://doi.org/10.1007/s12275-022-2007-1
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Abstract
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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 infectionrelated
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.
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Citations
Citations to this article as recorded by 
- Liver as a key organ for systemic antimicrobial defense
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Jeonghyun Lim, Heejoon Myung, Daejin Lim, Miryoung Song Journal of Biomedical Science.2024;[Epub] CrossRef - Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections
Feng Chen, Shan-Shan Wu, Chao Chen, Cheng Zhou World Journal of Hepatology.2024; 16(2): 177. CrossRef - Lipocalin-2 is an essential component of the innate immune response to Acinetobacter baumannii infection
Jessica R. Sheldon, Lauren E. Himmel, Dillon E. Kunkle, Andrew J. Monteith, K. Nichole Maloney, Eric P. Skaar, David S. Weiss PLOS Pathogens.2022; 18(9): e1010809. CrossRef
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