Evaluation of β-lactamase production and efflux pump overexpression in clinical isolates of Klebsiella pneumoniae and computational-network based hub genes identification.

AIM: This study aims to investigate the molecular mechanisms of multidrug resistance, especially β-lactamase and efflux pump-mediated resistance in clinical isolates of Klebsiella pneumoniae, and to analyze resistance genes using computational network for the identification of hub genes.

METHODS

The clinical isolates of K. pneumoniae were screened for phenotypic detection of β-lactamase production and efflux pump overexpression, followed by genotypic identification of resistant determinants present among the isolates. The data from molecular characterization were integrated with computational network analysis, and the hub genes were identified.

RESULTS

Phenotypic screening revealed a high occurrence of extended-spectrum β-lactamases (ESBL), AmpC, and metallo-β-lactamases, alongside overexpression of efflux pumps in the isolates. Molecular detection revealed the co-occurrence of β-lactamase genotypes with efflux pump genes in 46.25% of total isolates. Computational network analysis unveiled 97 functional partners forming five efficient clusters. Using CytoHubba, a total of 15 hub genes were identified from the network as central mediators of multidrug resistance in K. pneumoniae.

CONCLUSION

This study underscores the interplay of β-lactamase and efflux pump-mediated resistance mechanisms in the clinical isolates of K. pneumoniae and proposes the identified hub genes as potential candidate genes for target-based drug development strategies to confront the emerging pathogen.