Once chemically adjusted for use in animals, cilagicin consistently and safely eliminated Gram-positive bacteria in the lab, did not damage human cells, and successfully cured bacterial infections in mice.A brand-new antibiotic that was developed at
“Eons of evolution have given bacteria unique ways of engaging in warfare and killing other bacteria without their foes developing resistance,” says Brady, the Evnin Professor and head of the Laboratory of Genetically Encoded Small Molecules. Antibiotic drug discovery once largely consisted of scientists growing streptomyces or bacillus in the lab and bottling their secrets to treat human diseases.
Finding antibacterial genes in soil and cultivating them inside more lab-friendly bacteria is an alternate strategy that has been championed by the Brady lab for the last fifteen years. But even this approach has certain drawbacks. The majority of antibiotics come from genetic sequences that are locked within bacterial gene clusters named “biosynthetic gene clusters,” which work together to collectively code for a number of proteins.
Postdoctoral associates Zonggiang Wang and Bimal Koirala from the Brady lab began by searching through an enormous genetic-sequence database for promising bacterial genes that were predicted to be involved in killing other bacteria and hadn’t been examined previously. The “cil” gene cluster, which had not yet been explored in this context, stood out for its proximity to other genes involved in making antibiotics.