Entianin, a Novel Subtilin-Like Lantibiotic from Bacillus subtilis subsp. spizizenii DSM 15029 T with High Antimicrobial Activity
- 1 March 2011
- journal article
- Published by American Society for Microbiology in Applied and Environmental Microbiology
- Vol. 77 (5), 1698-1707
- https://doi.org/10.1128/aem.01962-10
Abstract
Lantibiotics, such as nisin and subtilin, are lanthionine-containing peptides that exhibit antimicrobial as well as pheromone-like autoinducing activity. Autoinduction is specific for each lantibiotic, and reporter systems for nisin and subtilin autoinduction are available. In this report, we used the previously reported subtilin autoinduction bioassay in combination with mass spectrometric analyses to identify the novel subtilin-like lantibiotic entianin from Bacillus subtilis subsp. spizizenii DSM 15029 T . Linearization of entianin using Raney nickel-catalyzed reductive cleavage enabled, for the first time, the use of tandem mass spectrometry for the fast and efficient determination of an entire lantibiotic primary structure, including posttranslational modifications. The amino acid sequence determined was verified by DNA sequencing of the etnS structural gene, which confirmed that entianin differs from subtilin at 3 amino acid positions. In contrast to B. subtilis ATCC 6633, which produces only small amounts of unsuccinylated subtilin, B. subtilis DSM 15029 T secretes considerable amounts of unsuccinylated entianin. Entianin was very active against several Gram-positive pathogens, such as Staphylococcus aureus and Enterococcus faecalis. The growth-inhibiting activity of succinylated entianin (S-entianin) was much lower than that of unsuccinylated entianin: a 40-fold higher concentration was required for inhibition. For succinylated subtilin (S-subtilin), a concentration 100-fold higher than that of unsuccinylated entianin was required to inhibit the growth of a B. subtilis test strain. This finding was in accordance with a strongly reduced sensing of cellular envelope stress provided by S-entianin relative to that of entianin. Remarkably, S-entianin and S-subtilin showed considerable autoinduction activity, clearly demonstrating that autoinduction and antibiotic activity underlie different molecular mechanisms.Keywords
This publication has 40 references indexed in Scilit:
- Microtiter plate bioassay to monitor the interference of antibiotics with the lipid II cycle essential for peptidoglycan biosynthesisJournal of Microbiological Methods, 2008
- 4-Chloro-α-cyanocinnamic acid is an advanced, rationally designed MALDI matrixProceedings of the National Academy of Sciences of the United States of America, 2008
- Lantibiotics: Peptides of Diverse Structure and FunctionAnnual Review of Microbiology, 2007
- Development and application of a microtiter plate-based autoinduction bioassay for detection of the lantibiotic subtilinJournal of Microbiological Methods, 2007
- Biosynthesis and Mode of Action of LantibioticsChemical Reviews, 2005
- Assembly and Stability of Nisin−Lipid II PoresBiochemistry, 2004
- Two Different Lantibiotic-Like Peptides Originate from the Ericin Gene Cluster of Bacillus subtilis A1/3Journal of Bacteriology, 2002
- Autoregulation of Nisin Biosynthesis in Lactococcus lactis by Signal TransductionPublished by Elsevier BV ,1995
- Nisin as a model food preservativeCritical Reviews in Food Science and Nutrition, 1994
- Bacillomycin: An Antibiotic from Bacillus subtilis Active against Pathogenic FungiExperimental Biology and Medicine, 1948