The increasing resistance of bacteria to conventional antimicrobial
therapy within both the nosocomial and community environment has enforced the urgent requirement for the discovery of novel agents. This has stimulated increased research efforts within the field of
lantibiotic discovery.
Lantibiotics are ribosomally synthesised, post-translationally modified
antimicrobial peptides that exhibit antimicrobial activity against a range of multi-
drug-resistant (MDR) bacteria. The success of these agents as a novel treatment of MDR
infections is exemplified by: the clinical development of
MU1140 (
mutacin 1140) and
NAI-107 (
microbisporicin), which are in late pre-clinical trials against gram-positive bacteria; NVB302 that has completed Phase I clinical trials for the treatment of
Clostridium difficile infections and;
duramycin that has completed Phase II clinical trials in the treatment of
cystic fibrosis. Despite these potential successes, the traditional method of
lantibiotic discovery involving the induction, production and identification is often an inefficient, time-consuming process creating a barrier to the efficient discovery of novel
lantibiotics. The introduction of novel and innovative identification methods, including the application of probes and the ability to improve the stability and activity of agents via mutagenesis offer encouraging new areas to explore. The rapid expansion of available genome sequences of a wide variety of bacteria has revealed multiple interesting
lantibiotic clusters that have the potential to be effective antimicrobials. However, due to the inefficient expression, screening and production methods currently employed, they are being assessed inefficiently and not rapidly enough to keep up with the ever-increasing demand for new agents.