Klebsiella pneumoniae derived outer membrane vesicles mediated bacterial virulence, antibiotic resistance, host immune responses and clinical applications

Abstract

Klebsiella pneumoniae is a gram-negative pathogen that can cause multiple diseases including sepsis, urinary tract infections, and pneumonia. The escalating detections of hypervirulent and antibiotic-resistant isolates are giving rise to growing public concerns. Outer membrane vesicles (OMVs) are spherical vesicles containing bioactive substances including lipopolysaccharides, peptidoglycans, periplasmic and cytoplasmic proteins, and nucleic acids. Emerging studies have reported various roles of OMVs in bacterial virulence, antibiotic resistance, stress adaptation, and host interactions, whereas knowledge on their roles in K. pneumoniae is currently unclear. In this review, we summarized recent progress on the biogenesis, components, and biological function of K. pneumoniae OMVs, the impact and action mechanism in virulence, antibiotic resistance, and host immune response. We also deliberated on the potential of K. pneumoniae OMVs in vaccine development, as diagnostic biomarkers, and as drug nanocarriers. In conclusion, K. pneumoniae OMVs hold great promise in the prevention and control of infectious diseases, which merits further investigation.

Keywords: Klebsiella pneumoniae; Outer membrane vesicles; clinical application; host immune responses; virulence.

Figure 1.

Characterization, biological functions, action mechanisms, and potential application of K. pneumoniae OMVs. The identification of OMVs mainly includes the morphology, size, and composition of OMVs. OMVs play roles in bacterial antibiotic resistance, virulence, pathogenesis, horizontal gene transfer, and host immune responses via different cells. OMVs are present in various body fluids after infection; hence, it may serve as a potential biomarker for the clinical identification of bacterial infection. OMVs are also utilized in the vaccine development and drug delivery to combat related infectious diseases. Drawn by BioRender and modified by Microsoft PowerPoint.

Figure 2.

Schematic figure of OMV formation by outer membrane blebbing in Klebsiella pneumoniae. Abbreviations: OM, out membrane; PG, peptidoglycan; IM, inner membrance. Drawn by BioRender and modified by Microsoft PowerPoint.

Figure 3.

Immune responses of host cells against Klebsiella pneumoniae outer membrane vesicles. (a) OMV–epithelial cell interaction. (b) OMV–macrophage interaction. OMVs consist of lipopolysaccharide (LPS), outer membrane proteins, porin, bacterial DNA, etc., which are recognized by host pathogen recognition receptors, such as the membrane-bound toll-like receptor 4 (TLR4), and induce a downstream immune response and the production of proinflammatory cytokines. The immune responses mainly include the activation of pattern recognition receptors, regulation of cytokine release pathways, inflammasome activation, and miRNA-mediated pathways. Abbreviations: OMV, out membrane vesicle; toll-like receptor 4, TLR4; OMVs isolated from multidrug-resistant K. pneumoniae treated with imipenem, KOMVs-imp. Drawn by Figdraw.