Lactate promote Klebsiella pneumoniae invasive infection by increasing capsular polysaccharide biosynthesis via PTS-CRP axis in liver abscess microenvironment

Abstract The global incidence of invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS) is increasing, yet the underlying molecular mechanisms remain elusive, hindering the development of effective therapeutic strategies. In this study, we analyzed bacterial molecular profiles and clinical data from patients with invasive and non-invasive KPLA infection, and found that no significant difference in the molecular characterization of K. pneumoniae isolate between the two groups while elevated serum lactate was observed as an independent predictor of invasive KPLA infection. Further study revealed that lactate promote K. pneumoniae invasive infection by enhancing capsular polysaccharide (CPS) biosynthesis. Mechanically, lactate reduced cyclic adenosine monophosphate (cAMP) levels by downregulating the expression of mannose-specific phosphotransferase system (man-PTS) enzyme II, and the reduction of cAMP positively regulated CPS biosynthesis by binding to the cAMP receptor protein (CRP). Our in vitro and in vivo experiments confirm lactate’s role in increasing CPS biosynthesis, offering new insights into the pathogenesis of IKPLAS.