Abstract
BackgroundThe catabolite control protein A (CcpA) is a master regulator of many important cellular processes in Gram-positive bacteria. In Lactobacillus plantarum, CcpA directly or indirectly controls the transcription of a large number of genes that are involved in carbohydrate metabolism, aerobic and anaerobic growth, stress response and metabolite production, but its role in response to different carbon sources remains unclear.ResultsHere a combined transcriptomic and physiological approach was used to survey the global alterations that occurred during the logarithmic growth phase of wild-type and ccpA mutant strains of L. plantarum ST-III using fructooligosaccharides (FOS) or glucose as the sole carbon source. The inactivation of ccpA significantly affected the growth and production of metabolites under both carbon sources. About 15% of the total genes were significantly altered between wild-type and ccpA strains grown on glucose and the value is deceased to 12% when these two strains were compared on FOS, while only 7% were obviously changed due to the loss of CcpA when comparing strains grown on glucose and FOS. Although most of the differentially expressed genes mediated by CcpA are glucose dependent, FOS can also induce carbon catabolite repression (CCR) through the CcpA pathway. Moreover, the inactivation of ccpA led to a transformation from homolactic fermentation to mixed fermentation under aerobic conditions. CcpA can control genes directly by binding in the regulatory region of the target genes (mixed fermentation), indirectly through local regulators (fatty acid biosynthesis), or have a double effect via direct and indirect regulation (FOS metabolism).ConclusionOverall, our results show that CcpA plays a central role in response to carbon source and availability of L. plantarum and provide new insights into the complex and extended regulatory network of lactic acid bacteria.
Highlights
The catabolite control protein A (CcpA) is a master regulator of many important cellular processes in Gram-positive bacteria
L. plantarum ST-III and its ccpA mutant were cultivated at 37 °C in chemically defined medium (CDM) medium containing glucose or FOS and the growth profiles during fermentation were compared (Fig. 1)
To compare and analyze the regulation of CcpA, we focused on three pair-wise comparisons: between wild-type and ccpA mutant grown on glucose, between wild-type and ccpA mutant grown on FOS, and between ccpA mutant cells grown on glucose and FOS
Summary
The catabolite control protein A (CcpA) is a master regulator of many important cellular processes in Gram-positive bacteria. In Lactobacillus plantarum, CcpA directly or indirectly controls the transcription of a large number of genes that are involved in carbohydrate metabolism, aerobic and anaerobic growth, stress response and metabolite production, but its role in response to different carbon sources remains unclear. Carbon catabolite repression (CCR) is one of the most fundamental and highly conserved mechanisms in both Gram-negative and Gram-positive bacteria [1]. This mechanism ensures optimal use of available nutrients. The CcpA-(Hpr-Ser-P) complex has an increased affinity for particular cis-acting DNA motifs, termed catabolite responsive elements (cre), and thereby represses or enhances gene expression, depending on the position of the cre in relation to the operator sequence [5]. CcpA is known to affect expression of ~ 15% of the genomes of numerous bacterial species [8], the contribution of direct versus indirect CcpA-mediated effects on transcription remains unclear
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