The Single Amino Acid Substitution in WcaJ(Ser332Leu) Promotes Hypervirulent Klebsiella Pneumoniae Resistant to Bacteriophage and Virulence Attenuated.

Authors

Lingrui Shi, Zhen Li, Li Xiang, Shiqi Tang, Hang Lai, Jiang Wu, Yingshun Zhou, Li Fu

Published in

Probiotics and antimicrobial proteins. Jul 07, 2026. Epub Jul 07, 2026.

Abstract

Amidst the rising antimicrobial resistance in hypervirulent Klebsiella pneumoniae (hvKP), phage therapy has emerged as a promising alternative. However, bacterial resistance to phages remains a critical challenge, with virulence attenuation representing a key characteristic of phage-resistant strains, albeit through incompletely elucidated mechanisms. This study investigated the phage-host interaction between phage vB_LZ2044 and hvKP strain NTUH-K2044, yielding a phage-resistant mutant PR_K2044. Comparative analysis revealed marked virulence attenuation in PR_K2044, accompanied by significant alterations in virulence-associated phenotypes, including capsular polysaccharide (CPS) production, lipopolysaccharide (LPS) integrity, urea metabolism, biofilm formation, and siderophore activity. Whole-genome sequencing (WGS) identified a singular nonsynonymous mutation (Ser332Leu) in the capsular synthesis regulator WcaJ. Transcriptomic analysis demonstrated coordinated regulation of multiple virulence-associated genes, including: CPS related genes (magA, wza, wzb, wzc, gnd, ugd, manB), LPS related genes (glf, wbbN, wbbO, wbbM, wzt, wabH), pili related genes (fimA, mrkC), outer membrane protein associated genes (ompA, acrB), nitrogen metabolism related genes (gcl, hyi, glxR, allB, allC, ureA), biofilm related gene fabZ and siderophore related gene ybtS. Our investigation integrating genomic, transcriptomic, and phenotypic analyses elucidates potential mechanisms underlying virulence attenuation and coordinated reprogramming in phage-resistant hvKP, providing critical insights for optimizing phage-based therapeutic strategies against multidrug-resistant pathogens and underscoring the need to consider adaptive trajectories when evaluating the therapeutic promise and evolutionary consequences of phage therapy.

PMID:
42412326
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.