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

Klebsiella pneumoniae is one of the most common causes of nosocomial infections, and the rise of drug-resistant K. pneumoniae strains is complicating treatment and contributing to a mounting global health crisis. K. pneumoniae has two pathotypes, classical (cKp) and hypervirulent (hvKp). CKp typically cause opportunistic infections in immunocompromised individuals in healthcare settings and often are 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 rmpADC operon is an hv-associated locus that confers hypermucoviscosity (HMV), a key virulence phenotype, and rmp genes are often found in convergent strains. In this study, we aimed to determine if the rmp genes alone could increase the virulence of classical strains in the absence of other hv-associated genes. We introduced genetically distinct rmp 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 rmp acquisition impacted the clinical isolates. Our results indicate that HMV is likely necessary but not sufficient for hypervirulence and that rmp sequence can influence virulence potential in classical strains.