Abstract - Saswati Biswas

A Strategy for Rapid Screening of Lantibiotics

Lantibiotics are ribosomally synthesized, extensively modified, short peptide antimicrobials.  In recent years, the need for new antibiotics has increased due to the rise of antibiotic resistance in pathogens.  Therefore, lantibiotics are also being explored for this purpose, and several of them are now in clinical and preclinical trials.  Lantibiotics are potent, and their targets are specific.  Thus, use of them does not harm the existing microbiota as a collateral damage.  Although a lantibiotic prepeptide is only ~60 residues comprised of leader and core regions, the biosynthesis gene cluster of a lantibiotic is organized in a large operon of ~10 kb in size.  The biosynthesis locus encodes the structural gene of the lantibiotic and all the necessary genes including the modification enzyme, exporter, immunity protein and occasionally the regulator.

The recent surge of genomics/metagenomics research boosted the availability of numerous novel lantibiotic sequences in GenBank and other public databases.  A vast majority of them are not characterized regarding their potency.  The predominant reason for the lack of characterization is that many sequences are derived from a metagenomic study of the microbial community.  Thus, isolated strains of lantibiotic producers are not available.  Occasionally, the lantibiotic producer strains are non-culturable.  Furthermore, many times, the lantibiotic genes are encoded as a part of a silent gene cluster.  To overcome these likely critical barriers, we examined the use of a heterologous expression system for screening of antimicrobials that are potentially novel lantibiotic-like peptides.  This remains practically an underexplored area of lantibiotic research.  Our model will utilize the lantibiotic biosynthesis machinery of the host and only integrate the core-lantibiotic gene (~32 residues) of the homologs in the host genome for synthesis and characterization.