'Omics technologies for the elucidation of the molecular mechanisms related to carbapenem-resistant and extended spectrum β-lactamase-producing Klebsiellapneumoniae.

Klebsiella pneumoniae is a Gram-negative bacterium and a major cause of nosocomial infections such as urinary tract infections (UTIs), pneumonia and meningitis. Although these infections are commonly treated with the β-lactam group of antibiotics and combinations of it, (multi-)drug resistance in K. pneumoniae has steadily increased in the last few decades. Resistance to the β-lactam class of antibiotics is primarily mediated through the activation of narrow and extended-spectrum β-lactamase enzymes and changes within the bacterial cell envelope. Antimicrobial Resistance (AMR) has become a large global public health problem and economic burden. Carbapenem-resistant and extended-spectrum β-lactamase-producing K. pneumoniae have been classified as critical pathogens for which improved diagnostics and treatments are urgently needed. In order to develop new diagnostics and treatments, the resistance profiles of K. pneumoniae on a molecular level needs to be understood. Despite the identification of several genes, transcripts, proteoforms and their associated roles in resistance mechanisms, global resistance phenotypes are steadily evolving and consequently lack comprehensive understanding. This review discusses the role of genomics, transcriptomics, and proteomics in understanding resistance mechanisms and the associated molecular characteristics using carbapenem-resistant and extended-spectrum β-lactamase-producing K. pneumoniae as a model pathogen to further our current understanding of AMR. Furthermore, we also highlight the need for a holistic approach (i.e., combining 'omics technologies and data) to provide an in-depth understanding of the global resistance phenotype of K. pneumoniae in AMR.