Clinical Implications of Genomic Adaptation and Evolution of Carbapenem-Resistant Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae poses a major challenge to healthcare worldwide as an important cause of multidrug-resistant infections. Nosocomial clones, including epidemic sequence type 258 (ST258), have shown an affinity for acquiring and disseminating resistance plasmids, particularly variants of the K. pneumoniae carbapenemase. By comparison, the resurgence of severe community-associated K. pneumoniae infections has led to increased recognition of hypervirulent strains belonging to the K1 and K2 capsular serotypes, predominantly in eastern Asia. Genomic and functional studies suggest that a variety of virulence and immune evasive factors contribute to the success of nosocomial and community-associated clonal lineages, aided by mechanisms of genetic plasticity that contribute to uptake of genes associated with antimicrobial resistance and pathogenicity. While there currently appears to be limited overlap between resistant and hypervirulent lineages, specific bacterial and host factors contributing to the emergence of dominant clones remain incompletely understood. This review summarizes recent advances in our understanding of the molecular epidemiology, virulence potential, and host-pathogen interactions of K. pneumoniae.

Keywords: K. pneumoniae; bacterial genomics; carbapenem resistance; immune evasion.

Figure 1.

Schematic summary of Klebsiella pneumoniae, host cell response, and intracellular signaling. Capsular polysaccharide plays a critical role in infection, antiphagocytosis, and evading the host innate immune pathways. Additional virulence factors include other outer membrane proteins and siderophores. Antimicrobial resistance contributes to worse outcomes but has limited overlap with markers of virulence. Plasmid-encoded antimicrobial resistance or virulence harbors the potential for novel hypervirulent carbapenem-resistant K. pneumoniae clones. Abbreviations: GM-CSF, granulocyte-macrophage colony-stimulating factor; IFNs, interferons; IRAK, IL-1 receptor-associated kinase; IL-12, interleukin 12; IL-17, interleukin 17, IL-23, interleukin 23; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κB; TLR, toll-like receptor.