Autophagy, cell death, and cytokines in K. pneumoniae infection: therapeutic perspectives

Abstract

Klebsiella pneumoniae is a notorious nosocomial pathogen causing a wide range of infections. The increasing trend of antimicrobial resistance obtained by the species immensely highly challenges the clinical treatment, representing a large threat to the global health care network. In particular, the recent convergence of multidrug resistance and hypervirulence in K. pneumoniae further worsens clinical outcomes, resulting in high mortality. Developments of new therapeutics become urgent, and immunotherapy based on antagonizing the anti-immune strategies of pathogens is a promising strategy, which requires the understanding of immune evasion mechanism in the context of the host–pathogen interactions. However, the underlying mechanisms employed by K. pneumoniae to counteract host immune responses, especially autophagy and cell death, have not been systematically reviewed and discussed yet. This review aims to summarize the tremendous progress that has been made to illuminate the landscape of cell signalling triggered by K. pneumoniae infection, especially in aspects of manipulating autophagy, cell death, and cytokine production.

Phenotypic characteristics and immune response of Procypris merus following challenge with aquatic isolate of Klebsiella pneumoniae

“…Capsular polysaccharides and LPS can form a complex on the surface of the bacterium through a complement‐mediated chain reaction that mediates bacterial evasion or resistance to be killed by the host's natural immunity (Krzyżewska‐Dudek et al., 2022). K. pneumoniae can be classified into 82 K serotypes according to the difference in capsular polysaccharides (K antigens), of which serotypes K1, K2 and K5 are closely related to serious infectious diseases in humans and animals (S. Wei, Xu, Chen, & Zhou, 2023), particularly K1 and K2 serotypes, which are highly virulent (Zhu et al., 2021). In this study, the magA gene was detected in K. pneumoniae ELD strains, which is a gene specific to K. pneumoniae serotype K1 (Fang et al., 2010).…”

Interactions and Implications of Klebsiella pneumoniae with Human Immune Responses and Metabolic Pathways: A Comprehensive Review

“…K. pneumoniae has the ability to activate autophagy, promoting the formation of neutrophil extracellular traps (NETs), a process that enhances the bactericidal effect of neutrophils. 21 However, K. pneumoniae also possesses the capability to interfere with the fusion of phagosomes and lysosomes, creating a relatively safe habitat within host cells.…”

Genome-wide association study of Klebsiella pneumoniae urinary tract infection in Taiwanese patients identifies potential genetic risk factors

“…Xu also reported that K. pneumoniae NdpA, which suppresses early hot in ammation, can be degraded by its host through ubiquitination [39]. Additionally, the association between host autophagy and ubiquitination initiated by K. pneumoniae infection was investigated [40]. A small ubiquitin-related modi er(SUMO) can be involved in various biological processes, including immunopathology and in ammation [41,42] dependent on the NF-κβ activation [43].…”