Structural change in GadD2 of Listeria monocytogenes field isolates supports nisin resistance

The lantibiotic nisin is used as a food additive to effectively inactivate a broad spectrum of Gram-positive bacteria such as Listeria monocytogenes. In total, 282 L. monocytogenes field isolates from German ready-to-eat food products, food-processing environments and patient samples and 39 Listeria reference strains were evaluated for their susceptibility to nisin. The MIC90 value was < 1500 IU ml(-1). Whole genome sequences (WGS) of four nisin susceptible (NS; growth < 200 IU ml(-1)) and two nisin resistant L. monocytogenes field isolates (NR; growth > 1500 IU ml(-1)) of serotype Ila were analyzed for DNA sequence variants (DSVs) in genes putatively associated with NR and its regulation. WGS of NR differed from NS in the gadD2 gene encoding for the glutamate decarboxylase system (GAD). Moreover, homology modeling predicted a protein structure of GadD2 in NR that promoted a less pH dependent GAD activity and may therefore be beneficial for nisin resistance. Likewise NR had a significant faster growth rate compared to NS in presence of nisin at pH 7. In conclusion, results contributed to ongoing debate that a genetic shift in GAD supports NR state.