Homoserine and quorum‐sensing acyl homoserine lactones as alternative sources of threonine: a potential role for homoserine kinase in insect‐stage Trypanosoma brucei. Issue 1 (25th November 2014)

• Record Type: Journal Article
• Authors: Ong, Han B.; Lee, Wai S.; Patterson, Stephen; Wyllie, Susan; Fairlamb, Alan H.
• Is Part Of: Molecular microbiology. Volume 95:Issue 1(2015)
• Page Start: 143
• Page End: 156
• Publication Date: 2014-11-25
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12853
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>D</italic> <italic>e novo</italic> synthesis of threonine from aspartate occurs via the β‐aspartyl phosphate pathway in plants, bacteria and fungi. However, the <italic>T</italic><italic>rypanosoma brucei</italic> 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 <italic>Tb</italic>HSK specifically phosphorylates L‐homoserine and displays kinetic properties similar to other HSKs. HSK null mutants generated in bloodstream forms displayed no growth phenotype <italic>in vitro</italic> or loss of virulence <italic>in vivo</italic>. 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 <italic>W</italic><italic>igglesworthia glossinidia</italic>) or all of the β‐aspartyl phosphate pathway (<italic>S</italic><italic>odalis glossinidius</italic>). In addition <italic>S</italic><italic>. glossinidius</italic> is known to produce 3‐oxohexanoylhomoserine lactone which also supports trypanosome growth. We propose that <italic>T</italic><italic>. brucei</italic> has retained HSK and threonine synthase in order to salvage these nutrients when threonine availability is limiting.</p> </abstract>