Exploring Novel Antibiotics by Targeting the GroEL/GroES Chaperonin System.

Abstract

Infectious diseases have affected 13.7 million patients, placing a heavy burden on society. Furthermore, inappropriate and unrequited utilization of antibiotics has led to antimicrobial resistance worldwide. However, well-established targeted screening of environmental isolates or compound libraries has produced limited new drugs. The current situation, in which drug development is delayed, bacterial evolution is occurring, and drug resistance is emerging, requires the development of new targets and/or new strategies to combat infections. Some novel antibacterial strategies have been proposed, among which disruption of protein balance by inhibiting transcription and translation machinery is one of the proven effective antimicrobial strategies. Molecular chaperonins could mediate the correct folding of proteins, especially under conditions such as high temperature and pressure. The GroEL/ES system has been confirmed as one of the key molecular chaperones for bacterial viability. Recent data have revealed the antibacterial activities of GroEL/ES-targeted compounds, highlighting the potential role of GroEL/ES in the development of novel antibiotics. In this brief review, we discuss the function of the GroEL/ES system and summarize the inhibitors of the GroEL/ES system. The GroEL/ES system may represent a promising drug target for the exploration of novel antibiotics.