In recent years, many infection cases caused by Klebsiella pneumoniae, leading to severe infections like liver abscess and bacteraemia, has increased due to the emergence of hypervirulent and antimicrobial resistant (AMR) strains (1). And β-lactam antibiotics are still recommended for the treatment of carbapenem-resistant K. pneumoniae infections (2). However, the growing resistance K. pneumoniae against β-lactam antibiotics demands comprehensive research into the underlying drug resistance mechanisms. It is demonstrated that outer membrane proteins (OMPs), specifically the major porins, play an important role in drug permeability, and the reduction of major porins has been correlated with resistance to β-lactams drugs. And based on the genome data, a high mutation rate is observed in some sequence types (e.g. ST258/512, ST15, ST101 and ST231) of K. pneumoniae belonging to common prevalent AMR clones worldwide. But, the regulatory mechanisms among the four major porins (OmpK35, OmpK36, OmpK37, and OmpK38) in β-lactam-resistant K. pneumoniae hasn’t been solved yet. This project aims to investigate the relationship between the porins-defeats mutation in OMPs (ompK35, ompK36, ompK37 and/or ompK38) and resistance to β-lactams in K. pneumoniae by utilizing a combination of experimental approaches and genome analysis to gain comprehensive insights into this topic.