Hypervirulent Klebsiella pneumoniae: Insights into Virulence, Antibiotic Resistance, and Fight Strategies Against a Superbug

Abstract

Community-acquired infections caused by Klebsiella pneumoniae (K. pneumoniae) have become a significant global health concern, particularly with the emergence of hypervirulent strains (hvKP). These strains are associated with severe infections, such as pyogenic liver abscesses, even in otherwise healthy individuals. Initially reported in Taiwan in the 1980s, hvKP has now spread worldwide. The pathogenicity of hvKP is attributed to an array of virulence factors that enhance its ability to colonize and evade host immune defenses. Additionally, the convergence of hypervirulence with antibiotic resistance has further complicated treatment strategies. As a member of the ESKAPE group of pathogens, K. pneumoniae exhibits high resistance to multiple antibiotics, posing a challenge for healthcare settings. This review provides a comprehensive overview of hvKP, highlighting its structural and pathogenic differences from classical K. pneumoniae strains, key virulence factors, mechanisms of antibiotic resistance, and the increasing threat of multidrug-resistant hvKP. Lastly, we discuss current treatment guidelines and emerging therapeutic strategies to combat this formidable pathogen.

Keywords: antibiotic resistance; hypervirulent Klebsiella pneumoniae; multidrug resistance; pathogenesis; treatment strategies.

Figure 1

Diseases caused by hvKP. It affects almost all systems and causes endophthalmitis, meningitis, necrotizing fasciitis, pyomylitis, osteomyelitis, pneumonia, bacteremia, hepatic abscess, urinary tract infection, and superficial infection. Created with BioRender.com (https://BioRender.com).

Figure 2

The cell wall structure of K. pneumoniae. Like most other gram-negative bacteria, it is composed of an outer membrane that contains lipopolysaccharide, periplasmic spaces, a thin layer of peptidoglycan, and a cytoplasmic membrane. Created with BioRender.com.

Figure 3

Protective functions of the hypercapsule in hypervirulent K. pneumoniae (hvKP). The hypercapsule in hvKP serves as a multifunctional defense structure, contributing to immune evasion and enhanced survival. It impairs phagocytic clearance, reduces susceptibility to host-derived antimicrobial peptides and therapeutic agents, and attenuates inflammatory responses by modulating cytokine production. Created with BioRender.com.

Figure 4

Iron acquisition by siderophores in hypervirulent Klebsiella pneumoniae (hvKP). Siderophores enable hvKP to overcome host nutritional immunity by sequestering iron from host iron-binding proteins. With superior iron-binding affinity, these molecules outcompete host proteins and facilitate iron uptake through dedicated bacterial receptors, supporting growth and virulence within the iron-limited environment of the host. Created with BioRender.com.