Sugar Import Suppresses Klebsiella pneumoniae Mucoidy in cAMP-CRP-dependent Manner

Klebsiella pneumoniae causes over 700,000 global deaths annually and this number continues to rise due to increasing antimicrobial resistance. Hypervirulent K. pneumoniae (hvKp) often causes severe invasive infections in community and hospital settings, typically originating from gut colonization. Capsular polysaccharide (CPS) and the associated features are a key hvKp virulence factor. Altering CPS properties, such as mucoidy, in response to environmental cues enhances K. pneumoniae fitness. Although several physical and nutrient cues influence mucoidy, the molecular mechanisms by which host-relevant signals, such as sugars, regulate this key CPS property remain undefined. Here, we show that sugar import, not catabolism, broadly suppresses hvKp mucoidy via cAMP-CRP signaling. Sugars suppress mucoidy by decreasing rmpADC promoter activity and the expression of the mucoidy regulator, rmpD. Moreover, this sugar-dependent regulation is conserved across multiple hvKp strains. hvKp associates with gut mucin and gut epithelial cells at a greater frequency when in a non-mucoid state. Together, our results suggest that sugar import broadly suppresses hvKp mucoidy and increases bacterial association to host cells.