Title |
Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection |
Author |
Daejin Lim1, Su-Jin Park2, Ha Young Kim3, Minsang Shin4, and Miryoung Song5* |
Address |
1Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea , 2Functional Bio-material Reasearch Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Republic of Korea, 3Department of Microbiology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea , 4Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea, 5Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin 17035, Republic of Korea |
Bibliography |
Journal of Microbiology, 60(4),444-449, 2022,
|
DOI |
10.1007/s12275-022-2007-1
|
Key Words |
lipocalin2, Acinetobacter baumannii, infection,
sepsis |
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 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. |