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Lactate promotes invasive Klebsiella pneumoniae liver abscess syndrome by increasing capsular polysaccharide biosynthesis via the PTS-CRP axis

Author

Listed:
  • Junying Zhu

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Guangyu Wang

    (Shanghai Jiao Tong University)

  • Wei Xi

    (Shanghai Jiao Tong University)

  • Zhen Shen

    (Shanghai Jiao Tong University)

  • Qing Wei

    (Shanghai Jiao Tong University)

  • Xiaoqiong Fang

    (Shanghai Jiao Tong University)

  • Min Li

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

Abstract

The global incidence of invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS) increases, yet its underlying molecular mechanisms remain elusive, hindering the development of effective therapeutic strategies. In this study, we analyze bacterial molecular profiles and clinical data from patients with KPLA and IKPLAS, and find no significant difference in the molecular characteristics of K. pneumoniae between the two groups, however, we identify elevated blood lactate levels as an independent predictor of IKPLAS. Further investigation reveals that lactate enhances K. pneumoniae virulence by promoting capsular polysaccharide (CPS) biosynthesis. Mechanistically, lactate reduces cyclic adenosine monophosphate (cAMP) levels by downregulating the expression of mannose-specific phosphotransferase system (man-PTS) enzyme IIA-D genes (gfrA, gfrB, gfrC and gfrD). This reduction in cAMP levels enhances CPS biosynthesis by decreasing its binding to the cAMP receptor protein (CRP). Our results highlight lactate’s role in enhancing the virulence of K. pneumoniae via the PTS-CRP axis, offering insights into the pathogenesis of IKPLAS.

Suggested Citation

  • Junying Zhu & Guangyu Wang & Wei Xi & Zhen Shen & Qing Wei & Xiaoqiong Fang & Min Li, 2025. "Lactate promotes invasive Klebsiella pneumoniae liver abscess syndrome by increasing capsular polysaccharide biosynthesis via the PTS-CRP axis," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61379-9
    DOI: 10.1038/s41467-025-61379-9
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    References listed on IDEAS

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