Genomic and functional characterization of a <i>bla</i> _NDM-1 and <i>tmexCD2-toprJ2</i> co-producing <i>Klebsiella quasipneumoniae</i> (KL159/ST1929) reveals plasmid-mediated suppression of virulence

<i>Klebsiella quasipneumoniae</i> has emerged as a multidrug-resistant (MDR) pathogen of growing clinical concern, driven by its capacity to acquire mobile genetic elements encoding carbapenemases and novel resistance determinants. This study aimed to characterize the genomic architecture, resistance profile, and phenotypic impact of plasmids in a clinical <i>K. quasipneumoniae</i> strain co-producing <i>bla</i>_NDM-1 and the tigecycline efflux pump gene cluster <i>tmexCD2-toprJ2</i>. Whole-genome sequencing and plasmid reconstruction were performed for strain KP10883 (KL159/ST1929). Antimicrobial susceptibility testing, plasmid curing, biofilm quantification, serum resistance assays, human lung epithelial cell infection assays, and <i>Galleria mellonella</i> infection models were used to evaluate the functional consequences of plasmid carriage. KP10883 harbored two functionally distinct plasmids: pKP10883-1, an IncU conjugative plasmid carrying <i>bla</i>_NDM-1 and <i>tmexCD2-toprJ2</i>, conferring broad-spectrum antibiotic resistance, and pKP10883-2, a nonconjugative IncFIB/IncFII plasmid encoding stability and adaptation modules without classical resistance genes. Curing of pKP10883-1 resulted in complete loss of resistance to β-lactams, carbapenems, and tigecycline, confirming plasmid-mediated resistance. Paradoxically, plasmid loss led to increased biofilm formation, enhanced serum resistance, greater epithelial cell adhesion and cytotoxicity, and higher virulence in <i>G. mellonella</i>, indicating suppression of chromosomal virulence by plasmid-borne regulatory elements. This study reveals a plasmid-mediated trade-off between antimicrobial resistance and virulence in <i>K. quasipneumoniae</i>. The functional complementarity of pKP10883-1 and pKP10883-2 supports their stable coexistence and reflects a broader adaptive strategy balancing drug resistance with pathogenic potential. These findings underscore the importance of considering the regulatory impact of MDR plasmids on host virulence in developing strategies against emerging MDR pathogens.IMPORTANCEThe emergence of multidrug-resistant (MDR) <i>Klebsiella quasipneumoniae</i> poses an escalating threat to clinical treatment and infection control. This study provides the first comprehensive genomic and functional characterization of a clinical <i>K. quasipneumoniae</i> strain co-harboring <i>bla</i>_NDM-1 and the tigecycline efflux pump cluster <i>tmexCD2-toprJ2</i>. By integrating genomic, phenotypic, and virulence analyses, we reveal a paradoxical trade-off in which plasmid acquisition confers extensive antibiotic resistance while suppressing host virulence. These findings uncover a novel plasmid-mediated regulatory mechanism balancing bacterial survival and pathogenicity. Understanding this interplay between resistance and virulence expands the current knowledge of MDR plasmid biology and provides valuable insights into how resistance evolution may reshape bacterial pathogenic potential-information critical for surveillance, therapeutic development, and containment of emerging high-risk <i>Klebsiella</i> lineages.