Homoserine and quorum-sensing acyl homoserine lactones as alternative sources of threonine

A potential role for homoserine kinase in insect-stage Trypanosoma brucei

Han B. Ong, Wai S. Lee, Stephen Patterson, Susan Wyllie, Alan H. Fairlamb

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    7 Citations (Scopus)
    16 Downloads (Pure)

    Abstract

    De novo synthesis of threonine from aspartate occurs via the β-aspartyl phosphate pathway in plants, bacteria and fungi. However, the Trypanosoma brucei genome encodes only the last two steps in this pathway: homoserine kinase (HSK) and threonine synthase. Here, we investigated the possible roles for this incomplete pathway through biochemical, genetic and nutritional studies. Purified recombinant TbHSK specifically phosphorylates L-homoserine and displays kinetic properties similar to other HSKs. HSK null mutants generated in bloodstream forms displayed no growth phenotype in vitro or loss of virulence in vivo. However, following transformation into procyclic forms, homoserine, homoserine lactone and certain acyl homoserine lactones (AHLs) were found to substitute for threonine in growth media for wild-type procyclics, but not HSK null mutants. The tsetse fly is considered to be an unlikely source of these nutrients as it feeds exclusively on mammalian blood. Bioinformatic studies predict that tsetse endosymbionts possess part (up to homoserine in Wigglesworthia glossinidia) or all of the β-aspartyl phosphate pathway (Sodalis glossinidius). In addition S.glossinidius is known to produce 3-oxohexanoylhomoserine lactone which also supports trypanosome growth. We propose that T.brucei has retained HSK and threonine synthase in order to salvage these nutrients when threonine availability is limiting.

    Original languageEnglish
    Pages (from-to)143-156
    Number of pages14
    JournalMolecular Microbiology
    Volume95
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2015

    Fingerprint

    homoserine kinase
    Acyl-Butyrolactones
    Homoserine
    Quorum Sensing
    Trypanosoma brucei brucei
    Threonine
    Insects
    Wigglesworthia
    Growth
    Tsetse Flies
    Food
    Trypanosomiasis
    Lactones
    Enterobacteriaceae
    Computational Biology
    Aspartic Acid
    Virulence
    Molecular Biology
    Fungi
    Genome

    Cite this

    @article{b60513312716420788c8b458919bf89e,
    title = "Homoserine and quorum-sensing acyl homoserine lactones as alternative sources of threonine: A potential role for homoserine kinase in insect-stage Trypanosoma brucei",
    abstract = "De novo synthesis of threonine from aspartate occurs via the β-aspartyl phosphate pathway in plants, bacteria and fungi. However, the Trypanosoma brucei genome encodes only the last two steps in this pathway: homoserine kinase (HSK) and threonine synthase. Here, we investigated the possible roles for this incomplete pathway through biochemical, genetic and nutritional studies. Purified recombinant TbHSK specifically phosphorylates L-homoserine and displays kinetic properties similar to other HSKs. HSK null mutants generated in bloodstream forms displayed no growth phenotype in vitro or loss of virulence in vivo. However, following transformation into procyclic forms, homoserine, homoserine lactone and certain acyl homoserine lactones (AHLs) were found to substitute for threonine in growth media for wild-type procyclics, but not HSK null mutants. The tsetse fly is considered to be an unlikely source of these nutrients as it feeds exclusively on mammalian blood. Bioinformatic studies predict that tsetse endosymbionts possess part (up to homoserine in Wigglesworthia glossinidia) or all of the β-aspartyl phosphate pathway (Sodalis glossinidius). In addition S.glossinidius is known to produce 3-oxohexanoylhomoserine lactone which also supports trypanosome growth. We propose that T.brucei has retained HSK and threonine synthase in order to salvage these nutrients when threonine availability is limiting.",
    author = "Ong, {Han B.} and Lee, {Wai S.} and Stephen Patterson and Susan Wyllie and Fairlamb, {Alan H.}",
    note = "This work was funded by the Wellcome Trust (grant numbers 079838 and 083481).",
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    T2 - A potential role for homoserine kinase in insect-stage Trypanosoma brucei

    AU - Ong, Han B.

    AU - Lee, Wai S.

    AU - Patterson, Stephen

    AU - Wyllie, Susan

    AU - Fairlamb, Alan H.

    N1 - This work was funded by the Wellcome Trust (grant numbers 079838 and 083481).

    PY - 2015/1/1

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    N2 - De novo synthesis of threonine from aspartate occurs via the β-aspartyl phosphate pathway in plants, bacteria and fungi. However, the Trypanosoma brucei genome encodes only the last two steps in this pathway: homoserine kinase (HSK) and threonine synthase. Here, we investigated the possible roles for this incomplete pathway through biochemical, genetic and nutritional studies. Purified recombinant TbHSK specifically phosphorylates L-homoserine and displays kinetic properties similar to other HSKs. HSK null mutants generated in bloodstream forms displayed no growth phenotype in vitro or loss of virulence in vivo. However, following transformation into procyclic forms, homoserine, homoserine lactone and certain acyl homoserine lactones (AHLs) were found to substitute for threonine in growth media for wild-type procyclics, but not HSK null mutants. The tsetse fly is considered to be an unlikely source of these nutrients as it feeds exclusively on mammalian blood. Bioinformatic studies predict that tsetse endosymbionts possess part (up to homoserine in Wigglesworthia glossinidia) or all of the β-aspartyl phosphate pathway (Sodalis glossinidius). In addition S.glossinidius is known to produce 3-oxohexanoylhomoserine lactone which also supports trypanosome growth. We propose that T.brucei has retained HSK and threonine synthase in order to salvage these nutrients when threonine availability is limiting.

    AB - De novo synthesis of threonine from aspartate occurs via the β-aspartyl phosphate pathway in plants, bacteria and fungi. However, the Trypanosoma brucei genome encodes only the last two steps in this pathway: homoserine kinase (HSK) and threonine synthase. Here, we investigated the possible roles for this incomplete pathway through biochemical, genetic and nutritional studies. Purified recombinant TbHSK specifically phosphorylates L-homoserine and displays kinetic properties similar to other HSKs. HSK null mutants generated in bloodstream forms displayed no growth phenotype in vitro or loss of virulence in vivo. However, following transformation into procyclic forms, homoserine, homoserine lactone and certain acyl homoserine lactones (AHLs) were found to substitute for threonine in growth media for wild-type procyclics, but not HSK null mutants. The tsetse fly is considered to be an unlikely source of these nutrients as it feeds exclusively on mammalian blood. Bioinformatic studies predict that tsetse endosymbionts possess part (up to homoserine in Wigglesworthia glossinidia) or all of the β-aspartyl phosphate pathway (Sodalis glossinidius). In addition S.glossinidius is known to produce 3-oxohexanoylhomoserine lactone which also supports trypanosome growth. We propose that T.brucei has retained HSK and threonine synthase in order to salvage these nutrients when threonine availability is limiting.

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