Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales

Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, beta-lactamase-mediated resistance does not spare even the most powerful beta-lactams (carbapenems), whose activity is challenged by carbapenemases. The dissemination of carbapenemases-encoding genes among Enterobacterales is a matter of concern, given the importance of carbapenems to treat nosocomial infections. Based on their amino acid sequences, carbapenemases are grouped into three major classes. Classes A and D use an active-site serine to catalyze hydrolysis, while class B (MBLs) require one or two zinc ions for their activity. The most important and clinically relevant carbapenemases are KPC, IMP/VIM/NDM, and OXA-48. However, several carbapenemases belonging to the different classes are less frequently detected. They correspond to class A (SME-, Nmc-A/IMI-, SFC-, GES-, BIC-like horizontal ellipsis ), to class B (GIM, TMB, LMB horizontal ellipsis ), class C (CMY-10 and ACT-28), and to class D (OXA-372). This review will address the genetic diversity, biochemical properties, and detection methods of minor acquired carbapenemases in Enterobacterales.

Automated summary

Gram-negative bacteria, especially Enterobacterales, play a significant role in global antimicrobial resistance, with resistance potentially affecting all major classes of anti-gram-negative agents and becoming multidrug resistant or even pan-drug resistant. Beta-lactamase-mediated resistance challenges even the most powerful beta-lactams like carbapenems, with dissemination of carbapenemases-encoding genes among Enterobacterales being a major concern. Different classes of carbapenemases, with varying biochemical properties and detection methods, contribute to the genetic diversity of acquired carbapenemases in Enterobacterales.