The Fructose-Specific Phosphotransferase System of Klebsiella pneumoniae Is Regulated by Global Regulator CRP and Linked to Virulence and Growth

Abstract

<i>Klebsiella pneumoniae</i> is an opportunistic pathogen, and its hypervirulent variants cause serious invasive community-acquired infections. A genomic view of <i>K. pneumoniae</i> NTUH-2044 for the carbohydrate phosphotransferase system (PTS) found a putative fructose PTS, namely, the Frw PTS gene cluster. The deletion mutant and the complemented mutant of <i>frwC</i> (KP1_1992), which encodes the putative fructose-specific enzyme IIC, were constructed, and the phenotypes were characterized. This transmembrane PTS protein is responsible for fructose utilization. <i>frwC</i> deletion can enhance biofilm formation and capsular polysaccharide (CPS) biosynthesis but decreases the growth rate and lethality in mice. <i>frw</i>C expression was repressed in the cyclic AMP receptor protein (CRP) mutant. Electrophoretic mobility shift assay showed that CRP can directly bind to the promoter of <i>frwC</i> These results indicated that <i>frwC</i> expression is controlled by CRP directly and that such regulation contributes to bacterial growth, CPS synthesis, and the virulence of the <i>Δcrp</i> strain. The findings help elucidate fructose metabolism and the CRP regulatory mechanism in <i>K. pneumoniae</i>.