Microbial Genomics: Innovative Targets and Mechanisms

Abstract

Multidrug resistance (MDR) has become an increasing threat to global health because bacteria can develop resistance to antibiotics over time. Scientists worldwide are searching for new approaches that go beyond traditional antibiotic discovery and development pipelines. Advances in genomics, however, opened up an unexplored therapeutic opportunity for the discovery of new antibacterial agents. Genomic approaches have been used to discover several novel antibiotics that target critical processes for bacterial growth and survival, including histidine kinases (HKs), LpxC, FabI, peptide deformylase (PDF), and aminoacyl-tRNA synthetases (AaRS). In this review, we will discuss the use of microbial genomics in the search for innovative and promising drug targets as well as the mechanisms of action for novel antimicrobial agents. We will also discuss future directions on how the utilization of the microbial genomics approach could improve the odds of antibiotic development having a more successful outcome.

Advances in Development of Novel Therapeutic Strategies against Multi-Drug Resistant Pseudomonas aeruginosa

“…Another two compounds, ACHN-975 [19,20] and PF-5081090 [21] (Figure 1 and Table 1), discovered later, exhibit extensive antimicrobial activity. These two LpxC inhibitors are more active against P. aeruginosa with lower minimal inhibitory concentration MIC 90 (0.5~1 µg/mL) and IC 50 (1.1 nM) than CHIR-090 [22,23]. However, few inhibitors of LpxC have reached clinical trials, largely due to the limited efficacy and unfavorable cardiovascular toxicity of the candidate inhibitors tested [24].…”