Enhanced ability to utilize alternative carbon sources drives a competitive advantage for a successful lineage of Klebsiella pneumoniae

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses critical threats to public health, with sequence type 11-capsular type 64 (ST11-KL64) CRKP dominating in China. By comparing the physical properties of ST11-KL64 and its parental lineage ST11-KL47 (capsular type 47), we identified that ST11-KL64 has a competitive advantage in gut colonization. Comparative genomics identified two genes, acyltransferase-encoding acyT and polysaccharide pyruvate transferase-encoding pyt, specific for ST11-KL64 with respect to ST11-KL47. The two genes function synergistically to drive this advantage, with acyT playing the dominant role. Mechanistically, pyt enhances adhesive and antioxidant capabilities, while acyT increases ABC transporter activity and carbon utilization efficiency. ST11-KL64 outcompetes ST11-KL47 through superior acquisition of ribose, rhamnose, and arabitol in the gut. These findings establish nutrient competition as a key driver of clonal success and identify nutrient restriction as a promising non-antimicrobial strategy to prevent CRKP colonization and infection.