Therapeutics
Figure 4
SPR741 potentiates the activity of antibiotics against E. coli ATCC 25922 (A), K. pneumoniae ATCC 43816 (B) and A. baumannii NCTC 12156 (C). The fold reduction in the MIC of each of 35 antibiotics is displayed at each of three concentrations of the Potentiator (2, 4, or 8µg/mL [A]; 4, 8, or 16µg/mL [B and C]). Corbett D. ‘Potentiation of Antibiotic Activity by a Novel Cationic Peptide, SPR741’. ASM Microbe 2016
Inc uses a proprietary chemistry technology to cre- ate novel antibiotics. Oppliotech Ltd uses compu- tational modelling to develop its new agents. Many of the drug development strategies fall along similar lines and target specific parts of the bacteria. Forge Therapeutics, Inc is developing small molecules
that
target a metalloenzyme
(LpxC) unique to bacteria. Redx Pharma Plc, MerLion Pharmaceuticals Pte Ltd and TaiGen Biotechnology Co Ltd all target novel bacterial topoisomerases; enzymes critical to the replication and transcription of bacterial DNA. Candidate molecules from MicuRx Pharmaceuticals Inc, Actelion Pharmaceuticals Ltd and Wockhardt Ltd disrupt a specific bacterial ribosome; cellular struc- tures where protein synthesis occurs.
The way forward
Bacteria have been evolving for billions of years and have a head start on us. A study of ancient bacteria recovered from Arctic permafrost found antibiotic resistance genes existed tens of thousands of years ago, having evolved to defend bacteria against the antibiotics made by other micro-organisms. After decades of a relatively more relaxed view in the fight against antibiotic-resistant bacteria, government and industry have a renewed, more aggressive focus. Most of the antibacterial molecules in use today came from microbes them- selves and may be considered the low hanging fruit. Scientists isolated antibiotics from nature and chemically tweaked them to produce related class- es of drugs. Fortunately, innovative strategies to attack bacteria are being pursued, giving us hope that the tide may be ready to turn in the battle against antibiotic resistance.
DDW
Dr Ankit Mahadevia is the CEO of Spero Therapeutics. He was formerly a Venture Partner in the life sciences group at Atlas Venture. In that capacity he supported the formation of eight com- panies focused on novel drug discovery platforms and therapeutic products, three of which he led as Acting CEO.
14 Drug Discovery World Summer 2017
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