Adaptive attenuation of virulence mediated by Wzc mutation in ST11-KL47 Carbapenemresistant Klebsiella pneumonia

Yufeng Dai ^1,2 Qiang Zhao ¹ Huanhuan Yan ^1,2 Kun Ye ¹ Lifeng Wang ¹ Ling Guo ¹ Na Guo ^1,2 Wenwen Li ^1,2 Jiyong Yang ^1*

• ¹ Department of Laboratory Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, China
• ² Medical school of Chinese PLA, Beijing, China

The impact of the hypermucoviscosity (HMV) phenotype in ST11-KL47 carbapenem-resistant Klebsiella pneumoniae (CRKp) pathogenicity warrants investigation for public health risk assessment. Among 230 clinical ST11-KL47 CRKp, the Wzc mutations are identified as the key to mucoviscosity acquisition. Unexpectedly, Wzc-mediated HMV CRKp exhibits reduced pathogenicity versus non-mucoviscosity (NMV) strains in different animal models, with competitive disadvantage, decreased biofilm formation, serum resistance, and adhesion, yet higher anti-phagocytic ability in vitro. Capsular polysaccharides (CPS) extraction and visualization of genome-engineered strains verify the Wzc mutations mediate HMV by standardizing CPS chain length and overproducing cellfree extracellular polysaccharides (cell-free EPS). Transcriptomic analysis and lipopolysaccharides (LPS) quantification reveal the downregulation of LPS in Wzc-mediated HMV strains. SEM results indicate the HMV potentially conceals the LPS and surface antigens anchored on the outer membrane. These findings demonstrate that the Wzc-induced HMV attenuates ST11-KL47 CRKp virulence by modifying the exopolysaccharide composition and physical distribution.