Bacterial Toxins Suggest New Antibiotic Targets

November 14, 2013 | To regulate their own growth and proliferation, bacteria maintain an intricate network of toxin-antitoxin (TA) systems, in which they produce a mix of toxins and targeted antitoxins that can skew toward a disruptive level of toxins in poor environmental conditions to limit growth. Some bacteria have been found to contain as many as 50 of these TA systems, all prepared to check bacterial growth should anything trigger a reduction in antitoxins. Michael Laub at MIT thinks his lab has found a particular TA system that could make a promising target for novel antibiotics significantly different from anything currently on the market. A toxin called SocB, when not mediated by antitoxin SocA, inhibits replication in Caulobacter crescentus by binding to a protein that participates in numerous crucial reactions in the replisome, playing roles in mismatch repair, translesion synthesis, and especially DNA replication itself. This protein, DnaN, is highly conserved across the bacterial kingdom, so compounds that mimic the binding properties of SocB could make for versatile antibiotics. Molecular Cell