Genomic and functional analysis ofrmplocus variants inKlebsiella pneumoniae

Abstract

AbstractBackgroundKlebsiella pneumoniaeis an opportunistic pathogen and a leading cause of healthcare-associated infections in hospitals, which are frequently antimicrobial resistant (AMR). Exacerbating the public health threat posed byK. pneumoniae, some strains also harbor additional hypervirulence determinants typically acquired via mobile genetic elements such as the well-characterised large virulence plasmid KpVP-1. ThermpADClocus is considered a key virulence feature ofK. pneumoniaeand is associated with upregulated capsule expression and the hypermucoid phenotype, which can enhance virulence by contributing to serum resistance. Typically such strains have been susceptible to all antimicrobials besides ampicillin, however the recent emergence of AMR hypermucoid strains is concerning.MethodsHere, we investigate the genetic diversity, evolution, mobilisation and prevalence ofrmpADC, in a dataset of 14000 genomes from isolates of theKlebsiella pneumoniaespecies complex, and describe the RmST virulence typing scheme for trackingrmpADCvariants for the purposes of genomic surveillance. Additionally, we examine the functionality of representatives for variants ofrmpADCintroduced into a mutant strain lacking its nativermpADClocus.ResultsThermpADClocus was detected in 7% of the dataset, mostly from genomes ofK. pneumoniaeand a very small number ofK. variicolaandK. quasipneumoniae. Sequence variants ofrmpADCgrouped into five distinct lineages (rmp1, rmp2, rmp2A, rmp3andrmp4) that corresponded to unique mobile elements, and were differentially distributed across different populations (i.e. clonal groups) ofK. pneumoniae. All variants were demonstrated to produce enhanced capsule production and hypermucoviscosity.ConclusionThese results provide an overview of the diversity and evolution of a prominentK. pneumoniaevirulence factor and support the idea that screening forrmpADCinK. pneumoniaeisolates and genomes is valuable to monitor the emergence and spread of hypermucoidK. pneumoniae, including AMR strains.