Background: Non-hypermucoviscous carbapenem-resistant Klebsiella pneumoniae  with enhanced virulence lacking hvKP-specific virulence factors is uncommon, and the virulence mechanisms of this organism are not understood.
Methods: Following a retrospective study of carbapenem-resistant K. pneumoniae  based on core genome multilocus sequence typing (cgMLST), isolates that caused high mortality were investigated with a genome-wide association study (GWAS), proteome analysis and an animal model.
Results: The subclone of sequence type 11 (ST11) K. pneumoniae , which belongs to complex type 3176 (CT3176) and K-locus 47 (KL47), was highlighted due to the high mortality of infected patients. GWAS analysis showed that transcriptional regulatory gene ampR  was associated with the CT3176 isolates. In a mouse model, the mortality, bacterial load and pathological changes of mice infected with ampR -carrying isolates were distinct from those infected with ampR -null isolates. The ampR  gene that enhances the virulence of the non-hypermucoviscous KL47 strain was unable to enhance the virulence of hypermucoviscous KL1 strain. Proteome analysis showed that the expression of WcaJ in the ampR ⁺ isolates was significantly higher than that in the ampR ⁻ isolates. Quantification of capsular polysaccharide confirmed that more capsule polysaccharide was produced by ampR⁺ and ampR -complementary strains compared to ampR⁻ strains. It is suggested that the enhancement of the initial stage of capsule synthesis may be the cause of the enhanced virulence of these non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae  isolates.
Conclusion: Non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae  with enhanced virulence warrants continued surveillance and investigation.
Keywords: Klebsiella pneumonia , virulence, carbapenem-resistant, capsule synthesis