title: Species-specific ant brain manipulation by a specialized fungal parasite.
abstract: BACKGROUND
  A compelling demonstration of adaptation by natural selection is the ability of parasites to manipulate host behavior. One dramatic example involves fungal species from the genus Ophiocordyceps that control their ant hosts by inducing a biting behavior. Intensive sampling across the globe of ants that died after being manipulated by Ophiocordyceps suggests that this phenomenon is highly species-specific. We advance our understanding of this system by reconstructing host manipulation by Ophiocordyceps parasites under controlled laboratory conditions and combining this with field observations of infection rates and a metabolomics survey.
  
  
  RESULTS
  We report on a newly discovered species of Ophiocordyceps unilateralis sensu lato from North America that we use to address the species-specificity of Ophiocordyceps-induced manipulation of ant behavior. We show that the fungus can kill all ant species tested, but only manipulates the behavior of those it infects in nature. To investigate if this could be explained at the molecular level, we used ex vivo culturing assays to measure the metabolites that are secreted by the fungus to mediate fungus-ant tissue interactions. We show the fungus reacts heterogeneously to brains of different ant species by secreting a different array of metabolites. By determining which ion peaks are significantly enriched when the fungus is grown alongside brains of its naturally occurring host, we discovered candidate compounds that could be involved in behavioral manipulation by O. unilateralis s.l.. Two of these candidates are known to be involved in neurological diseases and cancer.
  
  
  CONCLUSIONS
  The integrative work presented here shows that ant brain manipulation by O. unilateralis s.l. is species-specific seemingly because the fungus produces a specific array of compounds as a reaction to the presence of the host brain it has evolved to manipulate. These studies have resulted in the discovery of candidate compounds involved in establishing behavioral manipulation by this specialized fungus and therefore represent a major advancement towards an understanding of the molecular mechanisms underlying this phenomenon.
authors.forename: Charissa
authors.initials: C
authors.lastname: de Bekker
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Quevillon
authors.forename: Philip B
authors.initials: PB
authors.lastname: Smith
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Fleming
authors.forename: Debashis
authors.initials: D
authors.lastname: Ghosh
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Patterson
authors.forename: David P
authors.initials: DP
authors.lastname: Hughes
mesh_terms: D000818:Animals; D001000:Ants / Q000145:classification / Q000382:microbiology*; D001921:Brain / Q000382:microbiology; D006790:Host-Parasite Interactions; D006999:Hypocreales / Q000502:physiology*; D009656:North America; D013045:Species Specificity
references.citation: Dis Model Mech. 2013 Mar;6(2):516-20
references.pmid: 23104989
references.citation: Commun Integr Biol. 2011 Sep;4(5):598-602
references.pmid: 22046474
references.citation: Biochim Biophys Acta. 2006 Aug;1761(8):927-46
references.pmid: 16901751
references.citation: Fluids Barriers CNS. 2011 Feb 28;8(1):13
references.pmid: 21352605
references.citation: Mol Cell Biochem. 2003 Feb;244(1-2):57-62
references.pmid: 12701810
references.citation: Proc Biol Sci. 2006 Apr 22;273(1589):1023-30
references.pmid: 16627289
references.citation: Am Nat. 2009 Sep;174(3):424-33
references.pmid: 19627240
references.citation: Appl Environ Microbiol. 1990 Oct;56(10):3225-6
references.pmid: 2285324
references.citation: PLoS One. 2013 Aug 05;8(8):e70609
references.pmid: 23940603
references.citation: Mol Ecol. 2007 Apr;16(8):1701-11
references.pmid: 17402984
references.citation: J Insect Physiol. 2010 Nov;56(11):1611-6
references.pmid: 20570678
references.citation: Subcell Biochem. 2007;46:149-66
references.pmid: 18652076
references.citation: Biochim Biophys Acta. 2006 Dec;1758(12):2057-79
references.pmid: 16854371
references.citation: J Exp Biol. 2013 Jan 1;216(Pt 1):142-7
references.pmid: 23225877
references.citation: Neurosci Biobehav Rev. 2011 Jan;35(3):556-64
references.pmid: 20615430
references.citation: Rapid Commun Mass Spectrom. 2006;20(16):2447-62
references.pmid: 16871522
references.citation: Naturwissenschaften. 2004 Aug;91(8):386-90
references.pmid: 15278218
references.citation: Physiol Behav. 2003 Aug;79(3):441-9
references.pmid: 12954438
references.citation: PLoS One. 2011 Mar 02;6(3):e17024
references.pmid: 21399679
references.citation: Mol Cancer Ther. 2006 Feb;5(2):200-8
references.pmid: 16505092
references.citation: BMC Ecol. 2011 May 09;11:13
references.pmid: 21554670
references.citation: Rev Biol Trop. 2001 Sep-Dec;49(3-4):945-55
references.pmid: 12189826
references.citation: J Exp Biol. 2013 Jan 1;216(Pt 1):3-10
references.pmid: 23225861
references.citation: Biol Lett. 2011 Feb 23;7(1):67-70
references.pmid: 20719770
references.citation: Behav Processes. 2005 Mar 31;68(3):185-99
references.pmid: 15792688
references.citation: PLoS One. 2012;7(11):e45715
references.pmid: 23152747
references.citation: Insects. 2013 Jul 16;4(3):357-74
references.pmid: 26462424
references.citation: Nat Biotechnol. 2012 Sep;30(9):826-8
references.pmid: 22965049
references.citation: PLoS One. 2011;6(9):e23866
references.pmid: 21957440
references.citation: Mycol Res. 2009 Mar;113(Pt 3):279-89
references.pmid: 18938242
references.citation: Parasitology. 1994;109 Suppl:S119-38
references.pmid: 7854846
references.citation: Biochim Biophys Acta. 2006 Dec;1758(12):2139-47
references.pmid: 17094939
references.citation: PLoS One. 2009;4(3):e4835
references.pmid: 19279680
references.citation: Behav Brain Res. 2007 Feb 12;177(1):70-9
references.pmid: 17169442
references.citation: Infect Genet Evol. 2008 Jul;8(4):504-19
references.pmid: 17588825
references.citation: Annu Rev Entomol. 2009;54:189-207
references.pmid: 19067631
references.citation: J Exp Biol. 2013 Jan 1;216(Pt 1):120-6
references.pmid: 23225874
references.citation: Angew Chem Int Ed Engl. 2012 Mar 5;51(10):2368-70
references.pmid: 22287497