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Paradigm Shifts in Cell Wall Biogenesis Understanding

By October 4, 2018No Comments

Antibiotic resistance has become a major issue in recent years, and is believed to be directly linked to the livestock industry which accounts for ~80% of antibiotic use in North America. Frighteningly, this is expected to rise by nearly 70% globally by 2030 (Van Boeckel et al., PNAS, 2015). Coupled to its widespread and rising use, the development of novel antibiotics is in great decline, with no new classes of antibiotic having entered the clinic in the last 30 years (Silver, Clin Microbiol Rev, 2011). Since the majority of antibiotics in the clinic only inhibit a small subset of the potential bacterial targets, a major focus in the field is to discover and characterize novel targets.

The later stages of bacterial cell wall synthesis, have traditionally been targeted for antibacterial development, with over 50% of the antibiotics prescribed in the clinic designed to disrupt bacterial cell wall crosslinking. These approaches have been successful due to the importance of the cell wall in the strength and viability of bacteria, as well as having no counterpart in mammals. Therefore, it is of interest to pursue novel targets of bacterial cell wall biosynthesis that occur at different points in this complex pathway. One such example is the targeting of lipid recycling pathways, which are critical in cell-wall biosynthesis.