Unraveling the regulatory network of Lactobacillus plantarum WCFS1

M.W.W. Wels

Research output: Thesisinternal PhD, WU


The ability of Lactobacillus plantarum to adapt to various environmental conditions, even the variable, complex and competitive conditions of the mammalian intestinal tract, makes it an interesting subject for studying the mechanisms underlying niche-specific adaptation. The focus of this thesis was to unravel the regulatory network in L. plantarum using different bioinformatics tools. In many cases the generated hypotheses were validated using evidence gathered from genomics experiments. The regulatory network of L. plantarum was analyzed using four different approaches; one based on the annotation of the regulatory proteins encoded on the genome, while the three other methods predict conserved cis­-regulatory elements in the sequences upstream of encodes genes or Transcriptional Units (TUs). In the first method, putative locally-acting regulons were predicted using genome context conservation and complete genome hybridization (CGH) data. Comparison with genomes of other lactic acid bacteria revealed that L. plantarum has the highest relative fraction of its predicted proteome assigned to regulatory proteins and indicated that these differences can generally be related to regulatory protein families controlling the expression of genes related to adaptation to different or changing environments. The other three methods predicted conserved cis-acting regulatory elements, using different sources of information to initiate the search: i) the annotated genome sequence of L. plantarum WCFS1, ii) the annotated genome sequences of different sets of related bacterial species, and iii) multiple transcriptome datasets from a variety of experiments performed with L. plantarum WCFS1. Two of the regulatory motifs found in these large-scale analyses were studied in more detail. A total of 24 highly conserved, genetically linked motifs (8 – 34 nt) that form multiple mosaic L. plantarum supermotifs (LPSM) were found in the genome sequence of L. plantarum.  These LPSMs appear to be unique for L. plantarum but were found to be conserved among different L. plantarum strains. Although the function of these LPSMs remains unknown, transcriptome data suggested regulation of the expression in experiments comparing L. plantarum WCFS1 wild-type with a strain overexpressing endogenous genes from an expression plasmid. Phylogenetic footprinting, motif searching and RNA structure prediction procedures were employed to analyze the presence of T-box elements and their specifier codons in bacteria. The specifier codon of the various T-box elements was used to improve the functional annotation of approximately 125 genes in different bacterial genomes, including many genes that are notoriously difficult to annotate on basis of sequence similarity like amino acid transporters.  
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
  • de Vos, Willem, Promotor
  • Siezen, R.J., Promotor, External person
  • Kleerebezem, Michiel, Co-promotor
Award date7 Jan 2008
Place of Publication[S.l.]
Print ISBNs9789085047520
Publication statusPublished - 2008


  • lactobacillus plantarum
  • genetic regulation
  • genomics


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