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- Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection
- Daejin Lim , Su-Jin Park , Ha Young Kim , Minsang Shin , Miryoung Song
- J. Microbiol. 2022;60(4):444-449. Published online March 28, 2022
- DOI: https://doi.org/10.1007/s12275-022-2007-1
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- 3 Web of Science
- 3 Crossref
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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.
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Citations
Citations to this article as recorded by
- Antimicrobial peptide thanatin fused endolysin PA90 (Tha-PA90) for the control of Acinetobacter baumannii infection in mouse model
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
- Antimicrobial peptide thanatin fused endolysin PA90 (Tha-PA90) for the control of Acinetobacter baumannii infection in mouse model
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