Proteome profiling of carbapenem-resistant K. pneumoniae clinical isolate (NDM-4): Exploring the mechanism of resistance and potential drug targets.

The emergence of carbapenem resistance has become a major problem worldwide. This has made treatment of K. pneumoniae infections a difficult task. In this study, we have explored the whole proteome of the carbapenem-resistant Klebsiella pneumonia clinical isolate (NDM-4) under the meropenem stress. Proteomics (LC-MS/MS) and bioinformatics approaches were employed to uncover the novel mystery of the resistance over the existing mechanisms. Gene ontology, KEGG and STRING were used for functional annotation, pathway enrichment and protein-protein interaction (PPI) network respectively. LC-MS/MS analysis revealed that 52 proteins were overexpressed (≥10 log folds) under meropenem stress. These proteins belong to four major groups namely protein translational machinery complex, DNA/RNA modifying enzymes or proteins, proteins involved in carbapenems cleavage, modifications & transport and energy metabolism & intermediary metabolism-related proteins. Among the total 52 proteins 38 {matched to Klebsiella pneumonia subsp. pneumoniae (strain ATCC 700721/MGH 78578)} were used for functional annotation, pathways enrichment and protein-protein interaction. These were significantly enriched in the "intracellular" (14 of 38), "cytoplasm" (12 of 38) and "ribosome" (10 of 38). We suggest that these 52 over expressed proteins and their interactive proteins cumulatively contributed in survival of bacteria and meropenem resistance through various mechanisms or enriched pathways. These proteins targets and their pathways might be used for development of novel therapeutics against the resistance; therefore, the situation of the emergence of "bad-bugs" could be controlled.