Decoding virulence and resistance in Klebsiella pneumoniae: Pharmacological insights, immunological dynamics, and in silico therapeutic strategies

• Published in: Microbial pathogenesis Vol. 205; p. 107691
• Main Authors: Alishvandi, Ali, Barancheshemeh, Maryam, Firuzpour, Faezeh, Aram, Cena, Kamali, Mohammad Javad, Keikha, Masoud
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2025
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacterial Vaccines - immunology; beta-Lactamases - metabolism; Capsular polysaccharides; Computational biology; Computer Simulation; Drug Discovery; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Hypervirulent strains; Immune Evasion; Klebsiella Infections - drug therapy; Klebsiella Infections - immunology; Klebsiella Infections - microbiology; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - immunology; Klebsiella pneumoniae - pathogenicity; Virulence; Virulence Factors; Hypervirulent strains; Capsular polysaccharides; Immune evasion; Klebsiella pneumoniae; Computational biology
• ISSN: 0882-4010; 1096-1208; 1096-1208
• DOI: 10.1016/j.micpath.2025.107691

Klebsiella pneumoniae (K. pneumoniae) has become a serious global health concern due to its rising virulence and antibiotic resistance. As one of the leading members of ESKAPE pathogens, it plays a major role in a wide range of infections that cause pneumonia, urinary tract infections, and bacteremia, especially in immunocompromised and hospitalized patients. The recent increase in multidrug-resistant (MDR) and hypervirulent (hvKP) strains due to the production of extended-spectrum beta-lactamases (ESBLs) and carbapenemases, has greatly limited therapeutic options that highlights the need for novel approaches to combat the pathogen. This review outlines the virulence mechanisms, profiles of antibiotic resistance, and immune evasion strategies in K. pneumoniae. Also, it points out the role of capsular polysaccharides, lipopolysaccharides, and fimbriae in host colonization and immune evasion. Additionally, the review discusses the emerging therapeutic strategies of vaccine development, computational drug discovery, and the use of artificial intelligence (AI). The progress achieved in reverse vaccinology and structural biology enables the identification of new drug and vaccine targets, whereas AI and machine learning (ML) stand out as powerful candidates for high-throughput screening and drug design. However, challenges with antigenic variability, safety, and the need to collaborate globally still exist. This review focuses on the need for interdisciplinary approaches involving molecular biology and immunology with computational sciences to address K. pneumoniae infections and provide appropriate therapies in the era of antibiotic resistance. [Display omitted] •K. pneumoniae poses a global threat due to virulence & antibiotic resistance.•MDR & hvKP strains limit treatment options, demanding new therapies.•Capsular polysaccharides & fimbriae drive immune evasion & colonization.•AI & reverse vaccinology enable novel drug & vaccine target discovery.•Interdisciplinary strategies are key to combating K. pneumoniae infections.