Genomic tools to profile antibiotic mode of action

Abstract

The increasing emergence of antimicrobial multiresistant bacteria is of great concern to public health. While these bacteria are becoming an ever more prominent cause of nosocomial and community-acquired infections worldwide, the antibiotic discovery pipeline has been stalled in the last few years with very few efforts in the research and development of novel antibacterial therapies. Some of the root causes that have hampered current antibiotic drug development are the lack of understanding of the mode of action (MOA) of novel antibiotic molecules and the poor characterization of the bacterial physiological response to antibiotics that ultimately causes resistance. Here, we review how bacterial genetic tools can be applied at the genomic level with the goal of profiling resistance to antibiotics and elucidating antibiotic MOAs. Specifically, we highlight how chemical genomic detection of the MOA of novel antibiotic molecules and antibiotic profiling by next-generation sequencing are leveraging basic antibiotic research to unprecedented levels with great opportunities for knowledge translation.

• Antibiotic drug discovery
• bacterial genomics
• chemical genomics
• essential genes
• genomic libraries

Declaration of interest

Cardona’s research is supported by operating grants from the Manitoba Health and Research Council (MHRC), the Canadian Institutes of Health Research (CIHR)-Regional Partnership Program (RPP), a Natural Sciences and Engineering Research Council (NSERC) discovery grant program and Cystic Fibrosis Canada (CFC). CS holds a postdoctoral fellowship from MHRC. Samira Atoui was involved in figure design and file manipulation. The authors report no declarations of interest.