Lantibiotic immunity: inhibition of nisin mediated pore formation by NisI

Zainab AlKhatib; Marcel Lagedroste; Iris Fey; Diana Kleinschrodt; André Abts; Sander H J Smits

doi:10.1371/journal.pone.0102246

Lantibiotic immunity: inhibition of nisin mediated pore formation by NisI

PLoS One. 2014 Jul 11;9(7):e102246. doi: 10.1371/journal.pone.0102246. eCollection 2014.

Authors

Zainab AlKhatib¹, Marcel Lagedroste¹, Iris Fey¹, Diana Kleinschrodt¹, André Abts¹, Sander H J Smits¹

Affiliation

¹ Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Abstract

Nisin, a 3.4 kDa antimicrobial peptide produced by some Lactococcus lactis strains is the most prominent member of the lantibiotic family. Nisin can inhibit cell growth and penetrates the target Gram-positive bacterial membrane by binding to Lipid II, an essential cell wall synthesis precursor. The assembled nisin-Lipid II complex forms pores in the target membrane. To gain immunity against its own-produced nisin, Lactococcus lactis is expressing two immunity protein systems, NisI and NisFEG. Here, we show that the NisI expressing strain displays an IC50 of 73 ± 10 nM, an 8-10-fold increase when compared to the non-expressing sensitive strain. When the nisin concentration is raised above 70 nM, the cells expressing full-length NisI stop growing rather than being killed. NisI is inhibiting nisin mediated pore formation, even at nisin concentrations up to 1 µM. This effect is induced by the C-terminus of NisI that protects Lipid II. Its deletion showed pore formation again. The expression of NisI in combination with externally added nisin mediates an elongation of the chain length of the Lactococcus lactis cocci. While the sensitive strain cell-chains consist mainly of two cells, the NisI expressing cells display a length of up to 20 cells. Both results shed light on the immunity of lantibiotic producer strains, and their survival in high levels of their own lantibiotic in the habitat.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / immunology*
ATP-Binding Cassette Transporters / metabolism
Bacterial Proteins / genetics
Bacterial Proteins / immunology*
Bacterial Proteins / metabolism
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression Regulation, Bacterial / immunology*
Kinetics
Lactococcus lactis / genetics
Lactococcus lactis / immunology*
Lipoproteins / genetics
Lipoproteins / immunology*
Lipoproteins / metabolism
Membrane Proteins / genetics
Membrane Proteins / immunology*
Membrane Proteins / metabolism
Nisin / genetics
Nisin / immunology*
Nisin / metabolism
Protein Binding
Protein Structure, Tertiary
Recombinant Proteins / genetics
Recombinant Proteins / immunology
Recombinant Proteins / metabolism
Uridine Diphosphate N-Acetylmuramic Acid / analogs & derivatives
Uridine Diphosphate N-Acetylmuramic Acid / metabolism

Substances

ATP-Binding Cassette Transporters
Bacterial Proteins
Lipoproteins
Membrane Proteins
NisF protein, Lactococcus lactis
NisI protein, Lactococcus lactis
Recombinant Proteins
Uridine Diphosphate N-Acetylmuramic Acid
muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol
Nisin

Grants and funding

This work was supported by CLIB Graduate Cluster Industrial Biotechnology. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.