Adaptive laboratory evolution and proteomic insight on collateral sensitivity for meropenem in colistin-resistant Klebsiella pneumoniae

Background

Antimicrobial resistance (AMR) is a critical global challenge, with an estimated ≥10 million deaths per year by 2050. Klebsiella pneumoniae (K. pneumoniae), a critical priority bacterial pathogen, is rapidly developing resistance even against next-generation (meropenem) and last-resort (colistin) antibiotics, whereas the pipeline for discovery and development of new antibiotic(s) for treatment of antibiotic-resistant K. pneumoniae infections is a lengthy, resource-intensive, and costly process and hence demands exploring alternative and effective treatment strategies. Capitalizing on the simultaneous emergence of collateral sensitivity (CS) to resistant antibiotics can therefore be a rapid and effective strategy to fill the gap.

Methods