title: Characterization of the Antimicrobial Peptide Penisin, a Class Ia Novel Lantibiotic from Paenibacillus sp. Strain A3.
abstract: Attempts to isolate novel antimicrobial peptides from microbial sources have been on the rise recently, despite their low efficacy in therapeutic applications. Here, we report identification and characterization of a new efficient antimicrobial peptide from a bacterial strain designated A3 that exhibited highest identity with Paenibacillus ehimensis. Upon purification and subsequent molecular characterization of the antimicrobial peptide, referred to as penisin, we found the peptide to be a bacteriocin-like peptide. Consistent with these results, RAST analysis of the entire genome sequence revealed the presence of a lantibiotic gene cluster containing genes necessary for synthesis and maturation of a lantibiotic. While circular dichroism and one-dimension nuclear magnetic resonance experiments confirmed a random coil structure of the peptide, similar to other known lantibiotics, additional biochemical evidence suggests posttranslational modifications of the core peptide yield six thioether cross-links. The deduced amino acid sequence of the putative biosynthetic gene penA showed approximately 74% similarity with elgicin A and 50% similarity with the lantibiotic paenicidin A. Penisin effectively killed methicillin-resistant Staphylococcus aureus (MRSA) and did not exhibit hemolysis activity. Unlike other lantibiotics, it effectively inhibited the growth of Gram-negative bacteria. Furthermore, 80 mg/kg of body weight of penisin significantly reduced bacterial burden in a mouse thigh infection model and protected BALB/c mice in a bacteremia model entailing infection with Staphylococcus aureus MTCC 96, suggesting that it could be a promising new antimicrobial peptide.
authors.affiliation: CSIR Institute of Microbial Technology, Chandigarh, India.
authors.forename: Piyush
authors.initials: P
authors.lastname: Baindara
authors.affiliation: CSIR Institute of Microbial Technology, Chandigarh, India.
authors.forename: Vasvi
authors.initials: V
authors.lastname: Chaudhry
authors.affiliation: CSIR Institute of Microbial Technology, Chandigarh, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Mittal
authors.affiliation: Institute of Chemistry, Federal University of Goiás, Goiânia, Brazil.
authors.forename: Luciano M
authors.initials: LM
authors.lastname: Liao
authors.affiliation: Institute of Chemistry, Federal University of Goiás, Goiânia, Brazil.
authors.forename: Carolina O
authors.initials: CO
authors.lastname: Matos
authors.affiliation: CSIR Institute of Microbial Technology, Chandigarh, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Khatri
authors.affiliation: Centro de Analises Proteomicas e Bioquimicas, Pós-graduacão em Ciências Genomicas e Biotecnologia, Brasília, Brazil S-Inova, Programa de Pós-Graduacão em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, Brazil.
authors.forename: Octavio L
authors.initials: OL
authors.lastname: Franco
authors.affiliation: CSIR Institute of Microbial Technology, Chandigarh, India.
authors.forename: Prabhu B
authors.initials: PB
authors.lastname: Patil
authors.affiliation: CSIR Institute of Microbial Technology, Chandigarh, India suresh@imtech.res.in.
authors.forename: Suresh
authors.initials: S
authors.lastname: Korpole
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D001430:Bacteriocins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D015870:Gene Expression; D016680:Genome, Bacterial; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D005810:Multigene Family; D056507:Paenibacillus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C581110:paenicidin A; C000611449:penisin protein, Paenibacillus