title: A bacterial symbiont is converted from an inedible producer of beneficial molecules into food by a single mutation in the gacA gene.
abstract: Stable multipartite mutualistic associations require that all partners benefit. We show that a single mutational step is sufficient to turn a symbiotic bacterium from an inedible but host-beneficial secondary metabolite producer into a host food source. The bacteria's host is a "farmer" clone of the social amoeba Dictyostelium discoideum that carries and disperses bacteria during its spore stage. Associated with the farmer are two strains of Pseudomonas fluorescens, only one of which serves as a food source. The other strain produces diffusible small molecules: pyrrolnitrin, a known antifungal agent, and a chromene that potently enhances the farmer's spore production and depresses a nonfarmer's spore production. Genome sequence and phylogenetic analyses identify a derived point mutation in the food strain that generates a premature stop codon in a global activator (gacA), encoding the response regulator of a two-component regulatory system. Generation of a knockout mutant of this regulatory gene in the nonfood bacterial strain altered its secondary metabolite profile to match that of the food strain, and also, independently, converted it into a food source. These results suggest that a single mutation in an inedible ancestral strain that served a protective role converted it to a "domesticated" food source.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Stallforth
authors.forename: Debra A
authors.initials: DA
authors.lastname: Brock
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Cantley
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Tian
authors.forename: David C
authors.initials: DC
authors.lastname: Queller
authors.forename: Joan E
authors.initials: JE
authors.lastname: Strassmann
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001578:Benzopyrans / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D018389:Codon, Nonsense; D004023:Dictyostelium / Q000378:metabolism / Q000382:microbiology / Q000502:physiology*; D005809:Genes, Regulator / Q000235:genetics; D054884:Host-Pathogen Interactions; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D010802:Phylogeny; D011551:Pseudomonas fluorescens / Q000145:classification / Q000235:genetics* / Q000502:physiology; D011764:Pyrrolnitrin / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D033761:Spores, Protozoan / Q000378:metabolism / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D001578:Benzopyrans; D018389:Codon, Nonsense; C091100:GacA protein, Bacteria; D011764:Pyrrolnitrin
keywords: GacA–GacS two-component system; differential metabolomics; symbiosis
references.citation: Nature. 2005 May 5;435(7038):43-57
references.pmid: 15875012
references.citation: Appl Environ Microbiol. 2010 Aug;76(15):5263-8
references.pmid: 20525866
references.citation: Appl Environ Microbiol. 1994 Jun;60(6):2031-9
references.pmid: 16349289
references.citation: Nat Biotechnol. 2005 Jul;23(7):873-8
references.pmid: 15980861
references.citation: Environ Microbiol. 2010 Apr;12(4):899-915
references.pmid: 20089046
references.citation: Nat Prod Rep. 2000 Apr;17(2):157-64
references.pmid: 10821110
references.citation: Nature. 2005 Oct 6;437(7060):884-8
references.pmid: 16208371
references.citation: Res Microbiol. 1994 Jun-Aug;145(5-6):349-55
references.pmid: 7855419
references.citation: Proc Natl Acad Sci U S A. 2005 May 31;102(22):8006-11
references.pmid: 15911752
references.citation: Curr Opin Microbiol. 2012 Apr;15(2):118-24
references.pmid: 22172627
references.citation: Science. 2008 Oct 3;322(5898):63
references.pmid: 18832638
references.citation: Nat Prod Rep. 2009 Mar;26(3):338-62
references.pmid: 19240945
references.citation: Trends Genet. 2005 Jul;21(7):392-8
references.pmid: 15975432
references.citation: J Am Chem Soc. 2011 Nov 16;133(45):18343-9
references.pmid: 21928816
references.citation: Annu Rev Phytopathol. 2003;41:117-53
references.pmid: 12730389
references.citation: J Bacteriol. 1998 Dec;180(24):6635-41
references.pmid: 9852008
references.citation: Environ Microbiol. 2005 Nov;7(11):1686-97
references.pmid: 16232284
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14282-7
references.pmid: 21825172
references.citation: Trends Mol Med. 2006 Sep;12(9):415-24
references.pmid: 16890490
references.citation: Trends Genet. 2011 Feb;27(2):48-54
references.pmid: 21167620
references.citation: Curr Opin Biotechnol. 2001 Jun;12(3):289-95
references.pmid: 11404107
references.citation: J Biol Chem. 2007 Dec 7;282(49):35546-53
references.pmid: 17938167
references.citation: Mol Biol Evol. 2011 Oct;28(10):2731-9
references.pmid: 21546353
references.citation: Proc Natl Acad Sci U S A. 1981 Jul;78(7):4256-60
references.pmid: 6794030
references.citation: J Bacteriol. 2005 Jan;187(2):593-600
references.pmid: 15629930
references.citation: Nat Commun. 2013;4:2385
references.pmid: 24029835
references.citation: Nat Prod Rep. 2004 Aug;21(4):519-38
references.pmid: 15282634
references.citation: Annu Rev Genet. 2007;41:121-45
references.pmid: 18076326
references.citation: Nature. 2011 Jan 20;469(7330):393-6
references.pmid: 21248849
references.citation: Nat Chem Biol. 2009 Jun;5(6):391-3
references.pmid: 19330011
references.citation: Dev Cell. 2004 Nov;7(5):745-54
references.pmid: 15525535
references.citation: Mol Plant Microbe Interact. 2001 Dec;14(12):1351-63
references.pmid: 11768529
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5435-40
references.pmid: 18362345
references.citation: Nat Chem Biol. 2010 Apr;6(4):261-3
references.pmid: 20190763
references.citation: Gene. 1998 May 28;212(1):77-86
references.pmid: 9661666
references.citation: Bioinformatics. 2009 Aug 15;25(16):2078-9
references.pmid: 19505943
references.citation: Mol Biol Evol. 2008 Jan;25(1):83-91
references.pmid: 17940208