Carbapenems are a class of β-lactam antibacterial drugs with a broad antibacterial spectrum and strong activity, commonly used to treat serious bacterial infections. However, improper or excessive use of carbapenems can lead to increased bacterial resistance, which is a significant concern as they are often used as last resort for treating multidrug-resistant (MDR) gram-negative bacteria. Confronted with this challenge, it is crucial to comprehensively understand the mechanism of carbapenem resistance to develop effective therapeutic strategies and innovative drugs. In recent years, emerging research on the glycosylation of bacterial proteins has highlighted the crucial role of glycans in various bacterial processes, including carbapenem resistance. Given the limited understanding of bacterial glycosylation, its role in in carbapenem resistance may be more pivotal than currently acknowledged. In this review, we summarize the direct and multifunctional role of glycosylation in bacterial resistance as well as the classical and recently reported mechanisms of bacterial carbapenem resistance, focusing on illuminating the potential role of glycosylation in carbapenem resistance. We also discuss the potential of leveraging this knowledge to develop more effective strategies for combating clinically resistant bacteria.
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