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Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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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 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.

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Acknowledgements

This work was supported by the National Research Foundation of Korea grant funded by the Korean government (2021R1F1A1060072 and 2019M3E5D5066666), and by the Hankuk University of Foreign Studies Research Fund (of 2020). M.S. was supported by a National Research Foundation of Korea grant funded by the Korean government (MSIP) (2016R1D1A1B01008960). D.L. was supported by a National Research Foundation of Korea grant funded by the Korean government (MSIP) (NRF-2019R1C1C1003999).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, 24341, Republic of Korea

    Daejin Lim

  2. Functional Bio-material Reasearch Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, 56212, Republic of Korea

    Su-Jin Park

  3. Department of Microbiology, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea

    Ha Young Kim

  4. Department of Microbiology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea

    Minsang Shin

  5. Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin, 17035, Republic of Korea

    Miryoung Song

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  1. Daejin Lim
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Correspondence to Miryoung Song.

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All mouse experiments were carried out following guidelines of the Institutional Mouse Use and Care Committee of Chonnam National University (CNU IACUC-H-2021-15).

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Lim, D., Park, SJ., Kim, H.Y. et al. Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection. J Microbiol. 60, 444–449 (2022). https://doi.org/10.1007/s12275-022-2007-1

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  • DOI: https://doi.org/10.1007/s12275-022-2007-1

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