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Klebsiella pneumoniae, a major public health threat, resists antibiotics and can spread from the gut to the bloodstream, causing severe infections. Our study reveals how the immune system uses complement proteins C3 and C4 to block this spread. C3 limits bacterial growth in the gut through two potential mechanisms: (i) coating K. pneumoniae with fragments that signal bacteria-eating phagocytic cells to destroy it and (ii) recruiting more phagocytes into the gut. C3 also helps clear bacteria that escape into the blood. However, when antibiotic-resistant strains overgrow, C3 alone is insufficient. In these cases, C4 becomes critical, likely by enhancing C3’s ability to tag bacteria for elimination. This two-layered defense highlights new immune pathways that could be targeted to prevent bloodstream infections, especially in vulnerable patients or those colonized with drug-resistant bacteria. These insights open doors to innovative strategies against life-threatening Klebsiella infections.

Klebsiella pneumoniae 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 K. pneumoniae, conferred by the rmpADC locus. The rmp genes are encoded on mobile genetic elements and have been detected in convergent antibiotic-resistant K. pneumoniae strains of concern. In this study, we explored the impact of rmp 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 rmp-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.

Klebsiella pneumoniae (Kpn) is a Gram-negative opportunistic pathogen and a leading cause of hospital-acquired infections. The gastrointestinal (GI) tract serves as a critical site for Kpn colonizati....

This form can be used to register only or register+submit an abstract for the 2025 Klebsiella Seminar Series. By registering, you will receive a Zoom Webinar link for attendance prior to the event. Re...

February 2-4, 2025 Wintergreen Resort, Virginia

Klebsiella Virtual Seminar Series