Emergence of blaKPC-71 variant and loss of aerobactin-encoding genes (iucABCD-iutA) in ST11-K64 carbapenem-resistant Klebsiella pneumoniae during ceftazidime-avibactam treatment.

OBJECTIVE

To investigate the within-host evolutionary dynamics of resistance and virulence in carbapenem-resistant Klebsiella pneumoniae during ceftazidime-avibactam treatment.

METHODS

Three K. pneumoniae strains were isolated from the sputum of the same patient. Broth microdilution method, whole-genome sequencing and genetic analysis were employed to clarify the dynamics and mechanisms of antibiotic resistance. Galleria mellonella infection models were used to investigate the changes in virulence.

RESULTS

The study described the changes of three strains of ST11-K64 carbapenem-resistant K. pneumoniae associated with pulmonary infection in vivo. The transition from a ceftazidime-avibactam-susceptible but imipenem-resistant isolate (JXZRKP1) to a ceftazidime-avibactam-resistant but imipenem-susceptible isolate (JXZRKP2) was attributed to the transformation of the blaKPC gene from blaKPC-2 to blaKPC-71 and upregulation of blaKPC gene expression. Notably, the blaKPC-71 enzyme exhibited a Ser182 duplication compared to the wild-type blaKPC-2 carbapenemase. The blaKPC gene of three strains was carried by the IS26-mediated tandem core structure ISKpn27-blaKPC-IS1182 on an IncFII-type plasmid. Furthermore, in comparison with JXZRKP2, the virulence plasmid of JXZRKP3 lost the aerobactin-encoding genes (iucABCD-iutA), resulting in diminished virulence in G. mellonella infection models, but there was no significant difference(P > .05).

CONCLUSIONS

We first discovered that the mutation from blaKPC-2 to blaKPC-71 leads to resistance to ceftazidime-avibactam, followed by the loss of the aerobactin-encoding gene (iucABCD-iutA) on the virulence plasmid in vivo. This study underscores the complexity of addressing carbapenem-resistant K. pneumoniae infections.