Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination

Abstract

Severe liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence factors including an integrative, conjugative element ICEKp encoding the siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23’s evolutionary history, showing several deep-branching sublineages associated with distinct ICEKp acquisitions. Over 80% of liver abscess isolates belong to sublineage CG23-I, which emerged in ~1928 following acquisition of ICEKp10 (encoding yersiniabactin and colibactin), and then disseminated globally within the human population. CG23-I’s distinguishing feature is the colibactin synthesis locus, which reportedly promotes gut colonisation and metastatic infection in murine models. These data show circulation of CG23 K. pneumoniae decades before the liver abscess epidemic was first recognised, and provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae. To support such studies we present an open access, completely sequenced CG23-I human liver abscess isolate, SGH10.

Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives

“…Genetic inactivation of colibactin synthesis in a pks + K1 ST23 isolate reduced the ability of this hvKP strain to colonize the gut and disseminate to other organs in a murine model of systemic infection as well as to induce cell death in the brain during meningitis . Taken together, colibactin appears to support the colonization and pathogenesis of hvKp and may have contributed to the global spread of CG23 , of which K1 ST23 strains are prominent.…”

“…There are 14 different types of ICEs across hvKp, and genes encoding the siderophore yersiniabactin are a significant feature of most ICEs in cKp and hvKp strains . ICEs are extremely prevalent in hvKp lineages, including in nearly 90% of CG23 and close to three quarters of all hvKp strains . In addition to yersiniabactin genes, some ICEs carry other virulence genes; ICE Kp1 encodes rmpA and the siderophore salmochelin , and ICE Kp10 encodes colibactin synthetic genes .…”

“…There is a strong trend of co‐occurence of iro and iuc loci in hvKp strains in a recent analysis of ~ 2500 Kp genomes, suggesting salmochelin is present in these genomes because it is important to the success of hvKp as well . An additional analysis of 97 genomes of the CG23 hvKp clonal group detected ybt , iuc and iro loci in nearly all genomes .The host immune protein lipocalin‐2 can bind iron‐bound Ent and prevent its return to the cell in an attempt to thwart iron acquisition by bacteria. Ybt, Iuc and Iro are lipocalin‐2 resistant, suggesting these accessory siderophores in hvKp may help overcome restriction by lipocalin‐2 nutritional immunity, as observed for other Gram‐negative pathogens .…”

“…One major question regarding the convergence of hypervirulence and MDR is restricted acquisition of antibiotic resistance genes by hvKP relative to cKp strains. Large genomic analysis of hvKp has identified relatively low diversity of capsule types and overall genome diversity, despite the emergence of CG23 in the late 1800s . Others have speculated that there may be a barrier to horizontal gene transfer amongst hvKp clones which has largely limited acquisition of AR genes .…”

The rise of hyper‐virulence

“…describe well the case of hvKp for which only a few clonal groups have developed hyper‐virulence with CG23 being isolated in over 80% of liver abscesses caused by hvKp. CG23, emerging in the 1920th, have been increasingly reported since the 1980th and is now worldwide disseminated in the human population . Another well studied example is Pseudomonas aeruginosa .…”