Assessing the Contributions of the LiaS Histidine Kinase to the Innate Resistance of Listeria monocytogenes to Nisin, Cephalosporins, and Disinfectants

TheListeria monocytogenes LiaSR two-component system (2CS) encoded bylmo1021 andlmo1022 plays an important role in resistance to the food preservative nisin. A nonpolar deletion in the histidine kinase-encoding component (ΔliaS ) resulted in a 4-fold increase in nisin resistance. In contrast, the ΔliaS strain exhibited increased sensitivity to a number of cephalosporin antibiotics (and was also altered with respect to its response to a variety of other antimicrobials, including the active agents of a number of disinfectants). This pattern of increased nisin resistance and reduced cephalosporin resistance inL. monocytogenes has previously been associated with mutation of a second histidine kinase, LisK, which is a predicted regulator ofliaS and a penicillin binding protein encoded bylmo2229 . We noted thatlmo2229 transcription is increased in the ΔliaS mutant and in a ΔliaS ΔlisK double mutant and that disruption oflmo2229 in the ΔliaS ΔlisK mutant resulted in a dramatic sensitization to nisin but had a relatively minor impact on cephalosporin resistance. We anticipate that further efforts to unravel the complex mechanisms by which LiaSR impacts on the antimicrobial resistance ofL. monocytogenes could facilitate the development of strategies to increase the susceptibility of the pathogen to these agents.