The Origins of ST11 KL64 Klebsiella pneumoniae: a Genome-Based Study.

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major severe threat for human health, and its spread is largely driven by a few dominant lineages defined by sequence types (ST) and capsular (KL) types. ST11-KL64 is one such dominant lineage that is particularly common in China but also has a worldwide distribution. However, the population structure and origin of ST11-KL64 K. pneumoniae remain to be determined. We retrieved all K. pneumoniae genomes (n = 13,625, as of June 2022) from NCBI, comprising 730 ST11-KL64 strains. Phylogenomic analysis of core-genome single-nucleotide polymorphisms identified two major clades (I and II) plus an additional singleton of ST11-KL64. We performed dated ancestral reconstruction analysis using BactDating and found that clade I likely emerged in 1989 in Brazil, while clade II emerged around 2008 in eastern China. We then investigated the origin of the two clades and the singleton using a phylogenomic approach combined with analysis of potential recombination regions. We found that ST11-KL64 clade I is likely a hybrid with 91.2% (ca. 4.98 Mb) of the chromosome derived from the ST11-KL15 lineage and 8.8% (483 kb) acquired from ST147-KL64. In contrast, ST11-KL64 clade II was derived from ST11-KL47 with swapping of a 157-kb region (3% of the chromosome) containing the capsule gene cluster with clonal complex 1764 (CC1764)-KL64. The singleton also evolved from ST11-KL47 but with swapping of a 126-kb region with ST11-KL64 clade I. In conclusion, ST11-KL64 is a heterogenous lineage comprising two major clades and a singleton with different origins that emerged in different countries at different time points. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a severe threat globally and is associated with increased lengths of hospital stay and high mortality in affected patients. The spread of CRKP is largely driven by a few dominant lineages, including ST11-KL64, the dominant type in China with a worldwide distribution. Here, we tested the hypothesis that ST11-KL64 K. pneumoniae is a single genomic lineage by performing a genome-based study. However, we found that ST11-KL64 comprises a singleton and two major clades, which emerged in different countries in different years. In particular, the two clades and the singleton have different origins and acquired the KL64 capsule gene cluster from various sources. Our study underscores that the chromosomal region containing the capsule gene cluster is a hot spot of recombination in K. pneumoniae. This represents a major evolutionary mechanism employed by some bacteria for rapid evolution with novel clades that accommodate stress for survival.