The Classification of Carbapenemase Genes and Their Role in Bacterial Antimicrobial Resistance: A Review

Abstract

Antimicrobial resistance (AMR) is a significant worldwide health problem caused by antimicrobial overuse and misuse in different sectors, resulting in the appearance of resistant microbes. Other concerning is the concurrent emergence of dual carbapenem-colistin resistance, defined as no efficacy by both antibiotics that are reserved to treat life-threatening infections due to multidrug-resistant enterobacteriaceae. Carbapenemase genes encode β-lactamase enzymes capable of hydrolyzing carbapenems and other β-lactam antibiotics, offering high-level resistance and promoting treatment failure. This review focuses on molecular features, classification and pathogenic significance of the main carbapenemase genes in clinically important bacteria through data until October 2023. Carbapenemases are mainly classified into Ambler classes A, B, and D including major enzymatic family like KPC, OXA, IMP, VIM, and NDM type carbapenemases. the genes that encode carbapenemases often reside on mobile genetic elements that can be transferred horizontally at a high rate between bacterial species and are responsible for spreading carbapenem resistance globally. Besides their well-characterized links to antimicrobial resistance, emerging data suggest that carbapenemase genes can also influence bacterial pathogenesis through increased survival in the presence of antibiotic selective pressure, biofilm formation and co-transfer of virulence-associated determinants. It also emphasizes the clinical manifestations of infections with carbapenemase-producing pathogens, which are linked with increased morbidity and mortality, prolonged length of stay and greater healthcare costs. In line with observations made in some bacterial lineages, the co-existence of resistance and virulence traits highlights an urgent need to improve molecular surveillance, rapid diagnostic tools and efficient strategies for infection prevention. In addition, understanding the complex interactions between carbapenemase gene expression and bacterial fitness and host–pathogen dynamics is important for developing new therapeutic and preventive measures. There are many factors that facilitate the pathogenesis and antibiotic resistance of these organisms. To overcome this escalating public health challenge, it will then require integrated approaches between molecular epidemiology, antimicrobial stewardship and novel therapeutic strategies that together will alleviate the burden of carbapenemase-producing organisms on global health.

Keywords:

carbapenemases, antimicrobial resistance, β-lactam antibiotics

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