Disruption of a transcriptional repressor by an IS-element integration leads to the activation of a novel silent cellobiose transporter in Lactococcus lactis MG1363

L. lactis subsp. cremoris strains typically carry many dairy niche-specific adaptations. During adaptation to the milk environment these former plant strains have acquired various pseudogenes and insertion sequence elements indicative of ongoing genome decay and frequent transposition events in their genomes. Here, we describe the re-activation of a silenced plant sugar utilization cluster in an L. lactis MG1363 derivative lacking the two main cellobiose transporters PtcBACelB and PtcBAC upon applying selection pressure to utilize cellobiose. A disruption of the transcriptional repressor gene llmg_1239 by an IS element allows expression of the otherwise silent novel cellobiose transporter Llmg_1244 and leads to growth of mutant strains on cellobiose. Llmg_1239 was labeled CclR, for cellobiose cluster repressor.Importance Insertion sequences (IS) play an important role in the evolution of lactococci and other bacteria. They facilitate DNA rearrangements and are responsible for creation of new genetic variants with selective advantages under certain environmental conditions. L. lactis MG1363 possesses 71 copies in total of 11 different types of IS elements. This study describes yet another example of an IS-mediated adaptive evolution. An integration of IS981 or IS905 into a gene coding for a transcriptional repressor led to activation of the repressed gene cluster coding for a plant sugar utilization pathway. The expression of the gene cluster allowed assembly of a novel cellobiose-specific transporter and led to cell growth on cellobiose.