The acquisition of <i>rmpADC</i> can increase virulence of classical <i>Klebsiella pneumoniae</i> in the absence of other hypervirulence-associated genes

<i>Klebsiella pneumoniae</i> is one of the most common causes of nosocomial infections, and the rise of drug-resistant <i>K. pneumoniae</i> strains is complicating treatment and contributing to a mounting global health crisis. <i>K. pneumoniae</i> has two pathotypes: classical (cKp) and hypervirulent (hvKp). CKp typically causes opportunistic infections in immunocompromised individuals in healthcare settings and often is multi-drug resistant. HvKp can be community-acquired and cause high-mortality infections in immunocompetent individuals. Concerningly, antibiotic-resistant cKp strains with hypervirulence-associated genes and traits have recently emerged. Determining if and how hv-associated genes contribute to increased virulence of cKp strains is essential to addressing this growing threat. The <i>rmpADC</i> operon is an hv-associated locus that confers hypermucoviscosity (HMV), a key virulence phenotype, and <i>rmp</i> genes are often found in convergent strains. In this study, we aimed to determine if the <i>rmp</i> genes alone could increase the virulence of cKp strains in the absence of other hv-associated genes. We introduced genetically distinct <i>rmp</i> loci from different lineages into a broad array of cKp isolates and found that, while many isolates became HMV positive, only a subset of these strains showed an increase in virulence in a mouse model of pneumonia. Sequence type and capsule type were not predictive of how <i>rmp</i> acquisition impacted the clinical isolates. Our results indicate that HMV is likely necessary but not sufficient for hypervirulence and that <i>rmp</i> sequence can influence virulence potential in cKp strains.IMPORTANCE<i>Klebsiella pneumoniae</i> is a global pathogen, and gene exchange between hypervirulent (hvKp) and classical (cKp) strains is a rising threat. It is essential to understand how hvKp genes impact virulence phenotypes and identify the cKp strain backgrounds most amenable to enhanced virulence. Hypermucoviscosity (HMV) is a critical virulence factor in hypervirulent <i>K. pneumoniae</i>, conferred by the <i>rmpADC</i> locus. The <i>rmp</i> genes are encoded on mobile genetic elements and have been detected in convergent antibiotic-resistant <i>K. pneumoniae</i> strains of concern. In this study, we explored the impact of <i>rmp</i> acquisition in a broad set of classical clinical isolates. We observed that HMV appears necessary, but not sufficient, for increased virulence. Sequence type, capsule type, and HMV capacity could not predict which classical isolates gain an <i>rmp-</i>dependent colonization benefit. These insights increase our understanding of the distinctions between cKp and hvKp and further our ability to identify and treat new strains of concern.