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Transcriptome analysis reveals mechanisms by which Lactococcus lactis acquires nisin-resistance
Naomi E. Kramer, Sacha A.F.T. van Hijum, Jan Knol, Jan Kok and Oscar P. Kuipers*

Nisin, a post-translationally modified antimicrobial peptide produced by Lactococcus lactis, is widely used as a food preservative. Yet, the mechanisms leading to the development of nisin-resistance in bacteria is poorly understood. We used whole genome DNA-microarrays of L. lactis IL1403 to identify the factors underlying the acquired nisin-resistance mechanism. The transcriptomes of L. lactis IL1403 and L. lactis IL1403, which reached a 75-fold higher nisin-resistance level (NisR), were compared. Differential expression was observed in genes encoding proteins (putatively) involved in cell wall biosynthesis, energy metabolism, fatty acid and phospholipid metabolism, regulatory functions and metal- and/or peptide-transport and binding. These results were further substantiated by characterizing several knock-out and over-expression mutants. The acquired nisin-resistance mechanism in L. lactis is complex, involving various different mechanisms. Four major mechanisms are: (i) preventing nisin from reaching the cytoplasmic membrane, (ii) possibly transporting nisin across or out of the membrane, (iii) preventing insertion of nisin in the membrane and, (iv) reducing the acidity of the extracellular medium, thereby stimulating binding of nisin to the cell wall.

Supplementary files

General information on the data files (text)
IL1403 amplicon sequences0.5 Mb
TIF scans 36 Mb IL vs IL Nisin
Raw data after ArrayPro 4.5 analyses 1.2 Mb IL vs IL Nisin
Preprocessed data after PrePreP 0.9 Mb IL vs IL Nisin
Normalized data after PreP 0.2 Mb IL vs IL Nisin
Merged result tables after PostPreP 2 Mb IL vs IL Nisin
Output of the Cyber-T analysis 0.5 Mb IL vs IL Nisin