Overcoming phagocytosis resistance of hypervirulent Klebsiella pneumoniae by directly targeting capsules
Authors:Shogo Tsubaki1, Touya Toyomoto1, Rika Tanaka2,3, Jin Imai4,5, Juntaro Matsuzaki6,7, Katsuto Hozumi2 and Hitoshi Tsugawa1,5*
doi: 10.15698/mic2026.02.870
Volume 13, pp. 103 to 116, published 16/02/2026.
1 Transkingdom Signaling Research Unit, Division of Host Defense Mechanism, Tokai University School of Medicine; Isehara, Kanagawa, 259-1193, Japan. 2 Department of Immunology, Division of Host Defense Mechanism, Tokai University School of Medicine; Isehara, Kanagawa, 259-1193, Japan. 3 Department of Ophthalmology, Keio University School of Medicine; Shinjuku-ku, Tokyo, 160-8582, Japan. 4 Department of Clinical Health Science, Tokai University School of Medicine; Isehara, Kanagawa, 259-1193, Japan. 5 Institute of Medical Sciences, Tokai University; Isehara, Kanagawa, 259-1193, Japan. 6 Division of Interdisciplinary Genetics and Nanomedicine, Research Center for Drug Discovery, Keio University Faculty of Pharmacy; Minato-ku, Tokyo, 105-8512, Japan. 7 Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Keio University; Shinjuku-ku, Tokyo, 160-8582, Japan.
Keywords:
capsule synthesis, small RNA, phagocytosis, hypermucoviscosity assay, RmpA, Fur
Corresponding Author(s):
Conflict of interest statement:
H. Tsugawa received funding for joint research from Taiyo Kagaku Co. Ltd. and Tsumura Corporation. Funding agencies played no role in the study of design, data collection and analysis, decision to publish, or manuscript preparation.
Please cite this article as:
Shogo Tsubaki, Touya Toyomoto, Rika Tanaka, Jin Imai, Juntaro Matsuzaki, Katsuto Hozumi, Hitoshi Tsugawa (2026). Overcoming phagocytosis resistance of hypervirulent Klebsiella pneumoniae by directly targeting capsules. Microbial Cell 13: 103-116. doi: 10.15698/mic2026.02.870
© 2026 Tsubaki et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Capsular polysaccharides (CPS) are key virulence factors in Klebsiella pneumoniae and are closely associated with the K1 and K2 hypervirulent serotypes. Herein, we demonstrate that introducing nonspecific RNA (sgRNA) into K. pneumoniae ATCC43816 (Kp-pET-sgRNA), a K2 serotype strain classified as hypervirulent (hvKp), results in marked capsule loss and reduced hypermucoviscosity. Capsule loss and reduced hypermucoviscosity in Kp-pET-sgRNA were confirmed by comparison with the wild-type strain (Kp-WT) using transmission electron microscopy, hypermucoviscosity assays, and string tests. Mechanistically, we found that overexpression of sgRNA by introducing the pET-sgRNA plasmid led to gene deletion in the rmpADC operon, a key virulence determinant located on mobile chromosomal elements. Additionally, the mRNA expression of manC, which are chromosomal cps-related genes, was significantly repressed. In contrast, introduction of pET-sgRNA did not alter the mRNA expression of galF or wzi. The results revealed that capsule loss and reduced hypermucoviscosity in Kp-pET-sgRNA resulted from synergistic downregulation of both the rmpADC operon and manC. Loss of capsule synthesis and reduction of hypermucoviscosity in K. pneumoniae caused by sgRNA overexpression significantly decreased resistance to phagocytosis by macrophages but did not influence susceptibility to meropenem or colistin. The findings reveal an unexpected consequence of plasmid-mediated sgRNA introduction, where overexpression of sgRNA abolishes phagocytic resistance by disrupting capsule biosynthesis and reducing hypermucoviscosity in K. pneumoniae. This study highlights a promising strategy for disarming hypervirulent K. pneumoniae by directly targeting its key virulence factors and provides novel insights into antibacterial therapeutic approaches against this clinically significant pathogen.