Lactate promotes invasive Klebsiella pneumoniae liver abscess syndrome by increasing capsular polysaccharide biosynthesis via the PTS-CRP axis
Junying Zhu, Guangyu Wang, Wei Xi, Zhen Shen, Qing Wei, X. Fang, Min Li
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. 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.