Antibiotic resistance has emerged as a serious threat to global public health in recent years. Lack of novel antimicrobials, especially new classes of compounds, further aggravates the situation. For Gram-negative bacteria, their double layered cell envelope and an array of efflux pumps act as formidable barriers for antimicrobials to penetrate. While cytoplasmic targets are hard to reach, proteins in the periplasm are clearly more accessible, as the drug only needs to breach the outer membrane. In this review, we summarized recent efforts on the validation and testing of periplasmic proteins as potential antimicrobial targets and the development of related inhibitors that either inhibit the growth of a bacterial pathogen or reduce its virulence during interaction with host cells. We conclude that the periplasm contains a promising pool of novel antimicrobial targets that should be scrutinized more closely for the development of effective treatment against multidrug-resistant Gram-negative bacteria.
|Number of pages||18|
|Journal||ACS Infectious Diseases|
|State||Published - Sep 11 2020|
Bibliographical noteFunding Information:
This work is supported by NIH grant numbers 1R56AI137020 and 1R21AI142063-01, and NSF grant number CHE-1709381.
Copyright © 2020 American Chemical Society.
- Gram-negative bacterium
- antimicrobial resistance
- antimicrobial target
- efflux pump
ASJC Scopus subject areas
- Infectious Diseases