Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung.

Summary

Using clonal barcoding in pneumonia, the authors identify two dissemination modes for Klebsiella pneumoniae: metastatic dissemination driven by heterogeneous clonal expansion in the lung with high clonal similarity across organs, and direct dissemination with minimal expansion and low systemic burdens. Host and bacterial factors modulate clonal sharing and expansion, providing a framework for within-host bacteremia dynamics.

Key Findings

• Clonal barcoding identified two distinct dissemination modes: metastatic dissemination with heterogeneous clonal expansion in the lung and high inter-organ clonal similarity, and direct dissemination with minimal expansion.
• Systemic organ burdens and clonal similarity patterns corresponded to dissemination mode, with lower burdens and greater dissimilarity in direct dissemination.
• Both bacterial and host factors influenced clonal sharing and expansion dynamics during dissemination from pneumonia.

Clinical Implications

While preclinical, defining dissemination routes may guide development of interventions that limit clonal expansion or egress from the lung, informing preventive strategies against bacteremia.

Limitations

• Findings derived from murine pneumonia models may not fully generalize to human infections
• Focused on a single pathogen species; broader applicability to other pathogens remains to be tested

Future Directions

Define specific host and bacterial determinants of metastatic vs direct dissemination, and test interventions to disrupt clonal expansion or egress to reduce bacteremia.