Novel LanT Associated Lantibiotic Clusters Identified by Genome Database Mining

Mangal Singh,Dipti Sareen,Indranil Biswas

doi:10.1371/journal.pone.0091352

Abstract

BackgroundFrequent use of antibiotics has led to the emergence of antibiotic resistance in bacteria. Lantibiotic compounds are ribosomally synthesized antimicrobial peptides against which bacteria are not able to produce resistance, hence making them a good alternative to antibiotics. Nisin is the oldest and the most widely used lantibiotic, in food preservation, without having developed any significant resistance against it. Having their antimicrobial potential and a limited number, there is a need to identify novel lantibiotics.Methodology/FindingsIdentification of novel lantibiotic biosynthetic clusters from an ever increasing database of bacterial genomes, can provide a major lead in this direction. In order to achieve this, a strategy was adopted to identify novel lantibiotic biosynthetic clusters by screening the sequenced genomes for LanT homolog, which is a conserved lantibiotic transporter specific to type IB clusters. This strategy resulted in identification of 54 bacterial strains containing the LanT homologs, which are not the known lantibiotic producers. Of these, 24 strains were subjected to a detailed bioinformatic analysis to identify genes encoding for precursor peptides, modification enzyme, immunity and quorum sensing proteins. Eight clusters having two LanM determinants, similar to haloduracin and lichenicidin were identified, along with 13 clusters having a single LanM determinant as in mersacidin biosynthetic cluster. Besides these, orphan LanT homologs were also identified which might be associated with novel bacteriocins, encoded somewhere else in the genome. Three identified gene clusters had a C39 domain containing LanT transporter, associated with the LanBC proteins and double glycine type precursor peptides, the only known example of such a cluster is that of salivaricin.ConclusionThis study led to the identification of 8 novel putative two-component lantibiotic clusters along with 13 having a single LanM and 3 with LanBC genes. Putative lantibiotic clusters identified here hold the potential for the discovery of novel lantibiotic(s).

Highlights

Antibiotic compounds are in use for many decades in treating various bacterial infections and their continuous use has led to the development of drug resistant bacterial strains [1]
This study led to the identification of 8 novel putative two-component lantibiotic clusters along with 13 having a single LanM and 3 with LanBC genes
Putative lantibiotic clusters identified here hold the potential for the discovery of novel lantibiotic(s)

Summary

Introduction

Antibiotic compounds are in use for many decades in treating various bacterial infections and their continuous use has led to the development of drug resistant bacterial strains [1]. Cyclization occurs by linking cysteine to Dha or Dhb residues forming a thioether linkage called as lanthionine or b-methyllanthionine Lantibiotics exhibit their antibacterial activity by capturing lipid II precursor of peptidoglycan, inhibiting cell wall formation [4], or by pore formation which leads to leakage and disruption of the membrane potential [5]. Lantibiotic biosynthetic machinery is organized into gene clusters, in single or multiple operons encoding the precursor peptide(s), modification enzymes, immunity proteins, a protease and a transporter. Nisin is the oldest and the most widely used lantibiotic, in food preservation, without having developed any significant resistance against it Having their antimicrobial potential and a limited number, there is a need to identify novel lantibiotics

Methods

Results

Conclusion