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Lactate promotes invasive Klebsiella pneumoniae liver abscess syndrome by increasing capsular polysaccharide biosynthesis via the PTS-CRP axis
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Lactate promotes invasive Klebsiella pneumoniae liver abscess syndrome by increasing capsular polysaccharide biosynthesis via the PTS-CRP axis
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Journal Article
Lactate promotes invasive Klebsiella pneumoniae liver abscess syndrome by increasing capsular polysaccharide biosynthesis via the PTS-CRP axis
2025
Overview
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.
The molecular mechanism for invasive
Klebsiella pneumoniae
liver abscess syndrome (IKPLAS) remains poorly studied. Here, the authors demonstrate that the elevated blood lactate level is an independent predictor of IKPLAS by enhancing the virulence of
K. pneumoniae
via the PTS-CRP axis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/23
/ 45/77
/ 45/88
/ 45/91
/ 64/60
/ Aged
/ Animals
/ Bacterial Capsules - metabolism
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Blood
/ Cyclic AMP Receptor Protein - genetics
/ Cyclic AMP Receptor Protein - metabolism
/ Diabetes
/ Disease
/ Female
/ Gene Expression Regulation, Bacterial
/ Humanities and Social Sciences
/ Humans
/ Klebsiella Infections - blood
/ Klebsiella Infections - metabolism
/ Klebsiella Infections - microbiology
/ Klebsiella pneumoniae - drug effects
/ Klebsiella pneumoniae - genetics
/ Klebsiella pneumoniae - metabolism
/ Klebsiella pneumoniae - pathogenicity
/ Liver
/ Liver Abscess - microbiology
/ Male
/ Mannose
/ Mice
/ Polysaccharides, Bacterial - biosynthesis
/ Science
/ Sepsis
