title: Pneumococcal galactose catabolism is controlled by multiple regulators acting on pyruvate formate lyase.
abstract: Catabolism of galactose by Streptococcus pneumoniae alters the microbe's metabolism from homolactic to mixed acid fermentation, and this shift is linked to the microbe's virulence. However, the genetic basis of this switch is unknown. Pyruvate formate lyase (PFL) is a crucial enzyme for mixed acid fermentation. Functional PFL requires the activities of two enzymes: pyruvate formate lyase activating enzyme (coded by pflA) and pyruvate formate lyase (coded by pflB). To understand the genetic basis of mixed acid fermentation, transcriptional regulation of pflA and pflB was studied. By microarray analysis of ΔpflB, differential regulation of several transcriptional regulators were identified, and CcpA, and GlnR's role in active PFL synthesis was studied in detail as these regulators directly interact with the putative promoters of both pflA and pflB, their mutation attenuated pneumococcal growth, and their expression was induced on host-derived sugars, indicating that these regulators have a role in sugar metabolism, and multiple regulators are involved in active PFL synthesis. We also found that the influence of each regulator on pflA and pflB expression was distinct in terms of activation and repression, and environmental condition. These results show that active PFL synthesis is finely tuned, and feed-back inhibition and activation are involved.
authors.affiliation: Department of Infection, Immunity &Inflammation, University of Leicester, Leicester, LE1 9HN, UK.|Department of Biology, College of Education, University of Mosul, Iraq.
authors.forename: Firas A Y
authors.initials: FA
authors.lastname: Al-Bayati
authors.affiliation: Department of Infection, Immunity &Inflammation, University of Leicester, Leicester, LE1 9HN, UK.|Department of Biology, College of Education, University of Mosul, Iraq.
authors.forename: Hasan F H
authors.initials: HF
authors.lastname: Kahya
authors.affiliation: Department of Infection, Immunity &Inflammation, University of Leicester, Leicester, LE1 9HN, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Damianou
authors.affiliation: Molecular Genetics, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands.
authors.forename: Sulman
authors.initials: S
authors.lastname: Shafeeq
authors.affiliation: Molecular Genetics, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands.
authors.forename: Oscar P
authors.initials: OP
authors.lastname: Kuipers
authors.affiliation: Department of Infection, Immunity &Inflammation, University of Leicester, Leicester, LE1 9HN, UK.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.affiliation: Department of Infection, Immunity &Inflammation, University of Leicester, Leicester, LE1 9HN, UK.
authors.forename: Hasan
authors.initials: H
authors.lastname: Yesilkaya
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D004734:Energy Metabolism; D005690:Galactose / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008954:Models, Biological; D009154:Mutation; D011008:Pneumococcal Infections / Q000382:microbiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000502:physiology*; D059467:Transcriptome; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D000123:Acetyltransferases; C022560:formate C-acetyltransferase; D005690:Galactose