Expanded roles of lactate-sensing LldR in transcription regulation of the K-12 genome: lactate utilisation and acid resistance.

LldR is a lactate-responsive transcription factor (TF) that transcriptionally regulates the operon consisting of lactate permease and lactate dehydrogenase. The operon facilitates the utilisation of lactic acid in bacteria. However, the role of LldR in whole genomic transcriptional regulation, and the mechanism involved in adaptation to lactate remains unclear. We used genomic SELEX (gSELEX) to comprehensively analyse the genomic regulatory network of LldR to understand the overall regulatory mechanism of lactic acid adaptation of the model intestinal bacterium . In addition to the involvement of the operon in utilising lactate as a carbon source, genes related to glutamate-dependent acid resistance and altering the composition of membrane lipids were identified as novel targets of LldR. A series of and regulatory analyses led to the identification of LldR as an activator of these genes. Furthermore, the results of lactic acid tolerance tests and co-culture experiments with lactic acid bacteria suggested that LldR plays a significant role in adapting to the acid stress induced by lactic acid. Therefore, we propose that LldR is an l-/d-lactate sensing TF for utilising lactate as a carbon source and for resistance to lactate-induced acid stress in intestinal bacteria.