Understanding the evolution of macrolides resistance: a mini review

Macrolides inhibit the growth of bacterial cells by preventing the elongation of polypeptides during protein biosynthesis and includes natural, synthetic, and semisynthetic products. This occurs by blocking the passage of the polypeptide chain as macrolides bind at the nascent peptide exit tunnel. Recent data of ribosome profiling via ribo-seq further proves that other than blocking the polypeptide chain, macrolides are also able to affect the synthesis of individual proteins. Thus, this shows that the mode of action of macrolides is more complex than we initially thought. Since the discovery of macrolides in the 1950s, they have been widely used in veterinary, agriculture, and medicine. Due to misuse and overuse of antibiotics; bacteria have acquired resistance against them. Hence, it is of utmost importance for us to fully understand the mode of action of macrolides as well as the mechanism of resistance against macrolides to mitigate the antibiotic resistance issues. With a better understanding on the mode of actions of macrolides, chemical modifications can be performed to improve its potency. Furthermore, the complete detailed understanding of the mode of action of macrolides remained vague as new findings challenged the theory that was already in existence – due to this obscurity, research into macrolides' mode of action continues up to this day. In this review, we present an overview of macrolide antibiotics with the emphasis on the latest knowledge regarding the mode of action of macrolides and mechanism of resistance employed in bacteria against macrolides.