Identification of the Regulatory Logic Controlling Pathoadaptation by the SsrA-SsrB Two-Component System
Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world. Regulatory evolution, in which non-coding DNA is mutated to create new regulatory nodes, also contributes to this diversity to allow niche adaptation and the evolution of pathogenesis. To survive in the host environment, Salmonella enterica uses a type III secretion system and effector proteins, which are activated by the SsrA-SsrB two-component system in response to the host environment. To better understand the phenomenon of regulatory evolution in S. enterica, we defined the SsrB regulon and asked how this transcription factor interacts with the cis-regulatory region of target genes. Using ChIP-on-chip, cDNA hybridization, and comparative genomics analyses, we describe the SsrB-dependent regulon of ancestral and horizontally acquired genes. Further, we used a genetic screen and computational analyses integrating experimental data from S. enterica and sequence data from an orthologous regulatory system in the insect endosymbiont, Sodalis glossinidius, to identify the conserved yet flexible palindrome sequence that defines DNA recognition by SsrB. Mutational analysis of a representative promoter validated this palindrome as the minimal architecture needed for regulatory input by SsrB. These data provide a high-resolution map of a regulatory network and the underlying logic enabling pathogen adaptation to a host.
Vyšlo v časopise:
Identification of the Regulatory Logic Controlling Pathoadaptation by the SsrA-SsrB Two-Component System. PLoS Genet 6(3): e32767. doi:10.1371/journal.pgen.1000875
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1000875
Souhrn
Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world. Regulatory evolution, in which non-coding DNA is mutated to create new regulatory nodes, also contributes to this diversity to allow niche adaptation and the evolution of pathogenesis. To survive in the host environment, Salmonella enterica uses a type III secretion system and effector proteins, which are activated by the SsrA-SsrB two-component system in response to the host environment. To better understand the phenomenon of regulatory evolution in S. enterica, we defined the SsrB regulon and asked how this transcription factor interacts with the cis-regulatory region of target genes. Using ChIP-on-chip, cDNA hybridization, and comparative genomics analyses, we describe the SsrB-dependent regulon of ancestral and horizontally acquired genes. Further, we used a genetic screen and computational analyses integrating experimental data from S. enterica and sequence data from an orthologous regulatory system in the insect endosymbiont, Sodalis glossinidius, to identify the conserved yet flexible palindrome sequence that defines DNA recognition by SsrB. Mutational analysis of a representative promoter validated this palindrome as the minimal architecture needed for regulatory input by SsrB. These data provide a high-resolution map of a regulatory network and the underlying logic enabling pathogen adaptation to a host.
Zdroje
1. OchmanH
LawrenceJG
GroismanEA
2000 Lateral gene transfer and the nature of bacterial innovation. Nature 405 299 304
2. NavarreWW
PorwollikS
WangY
McClellandM
RosenH
2006 Selective silencing of foreign DNA with low GC content by the H-NS protein in Salmonella. Science 313 236 238
3. LucchiniS
RowleyG
GoldbergMD
HurdD
HarrisonM
2006 H-NS mediates the silencing of laterally acquired genes in bacteria. PLoS Pathog 2 e81 doi:10.1371/journal.ppat.0020081
4. Prud'hommeB
GompelN
CarrollSB
2007 Emerging principles of regulatory evolution. Proc Natl Acad Sci U S A 104 Suppl 1 8605 8612
5. StoneJR
WrayGA
2001 Rapid evolution of cis-regulatory sequences via local point mutations. Mol Biol Evol 18 1764 1770
6. MayoAE
SettyY
ShavitS
ZaslaverA
AlonU
2006 Plasticity of the cis-regulatory input function of a gene. PLoS Biol 4 e45 doi:10.1371/journal.pbio.0040045
7. IsalanM
LemerleC
MichalodimitrakisK
HornC
BeltraoP
2008 Evolvability and hierarchy in rewired bacterial gene networks. Nature 452 840 845
8. PerezJC
GroismanEA
2009 Evolution of transcriptional regulatory circuits in bacteria. Cell 138 233 244
9. SheaJE
HenselM
GleesonC
HoldenDW
1996 Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. Proc Natl Acad Sci U S A 93 2593 2597
10. OchmanH
SonciniFC
SolomonF
GroismanEA
1996 Identification of a pathogenicity island required for Salmonella survival in host cells. Proc Natl Acad Sci USA 93 7800 7804
11. CornelisGR
2006 The type III secretion injectisome. Nat Rev Microbiol 4 811 825
12. GalanJE
Wolf-WatzH
2006 Protein delivery into eukaryotic cells by type III secretion machines. Nature 444 567 573
13. FassE
GroismanEA
2009 Control of Salmonella pathogenicity island-2 gene expression. Curr Opin Microbiol 12 199 204
14. YoonH
McDermottJE
PorwollikS
McClellandM
HeffronF
2009 Coordinated regulation of virulence during systemic infection of Salmonella enterica serovar Typhimurium. PLoS Pathog 5 e1000306 doi:10.1371/journal.ppat.1000306
15. RytkonenA
PohJ
GarmendiaJ
BoyleC
ThompsonA
2007 SseL, a Salmonella deubiquitinase required for macrophage killing and virulence. Proc Natl Acad Sci U S A 104 3502 3507
16. CoombesBK
WickhamME
LowdenMJ
BrownNF
FinlayBB
2005 Negative regulation of Salmonella pathogenicity island 2 is required for contextual control of virulence during typhoid. Proc Natl Acad Sci U S A 102 17460 17465
17. BrownNF
VallanceBA
CoombesBK
ValdezY
CoburnBA
2005 Salmonella Pathogenicity Island 2 is expressed prior to penetrating the intestine. PLoS Pathog 1 e32 doi:10.1371/journal.ppat.0010032
18. OchmanH
GroismanEA
1996 Distribution of pathogenicity islands in Salmonella spp. Infect Immun 64 5410 5412
19. OsborneSE
WalthersD
TomljenovicAM
MulderDT
SilphaduangU
2009 Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function. Proc Natl Acad Sci U S A 106 3982 3987
20. CoombesBK
BrownNF
ValdezY
BrumellJH
FinlayBB
2004 Expression and secretion of Salmonella pathogenicity island-2 virulence genes in response to acidification exhibit differential requirements of a functional type III secretion apparatus and SsaL. J Biol Chem 279 49804 49815
21. HokampK
RocheFM
AcabM
RousseauME
KuoB
2004 ArrayPipe: a flexible processing pipeline for microarray data. Nucleic Acids Res 32 W457 459
22. TatusovRL
NataleDA
GarkavtsevIV
TatusovaTA
ShankavaramUT
2001 The COG database: new developments in phylogenetic classification of proteins from complete genomes. Nucleic Acids Res 29 22 28
23. McClellandM
SandersonKE
SpiethJ
CliftonSW
LatreilleP
2001 Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413 852 856
24. DobrindtU
HochhutB
HentschelU
HackerJ
2004 Genomic islands in pathogenic and environmental microorganisms. Nat Rev Microbiol 2 414 424
25. FengX
WalthersD
OropezaR
KenneyLJ
2004 The response regulator SsrB activates transcription and binds to a region overlapping OmpR binding sites at Salmonella pathogenicity island 2. Mol Microbiol 54 823 835
26. WalthersD
CarrollRK
NavarreWW
LibbySJ
FangFC
2007 The response regulator SsrB activates expression of diverse Salmonella pathogenicity island 2 promoters and counters silencing by the nucleoid-associated protein H-NS. Mol Microbiol 65 477 493
27. MengX
BrodskyMH
WolfeSA
2005 A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors. Nat Biotechnol 23 988 994
28. ZwirI
ShinD
KatoA
NishinoK
LatifiT
2005 Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica. Proc Natl Acad Sci U S A 102 2862 2867
29. BaileyTL
WilliamsN
MislehC
LiWW
2006 MEME: discovering and analyzing DNA and protein sequence motifs. Nucleic Acids Res 34 W369 373
30. LiuXS
BrutlagDL
LiuJS
2002 An algorithm for finding protein-DNA binding sites with applications to chromatin-immunoprecipitation microarray experiments. Nat Biotechnol 20 835 839
31. TohH
WeissBL
PerkinSA
YamashitaA
OshimaK
2006 Massive genome erosion and functional adaptations provide insights into the symbiotic lifestyle of Sodalis glossinidius in the tsetse host. Genome Res 16 149 156
32. CarrollRK
LiaoX
MorganLK
CicirelliEM
LiY
2009 Structural and functional analysis of the C-terminal DNA binding domain of the Salmonella typhimurium SPI-2 response regulator SsrB. J Biol Chem 284 12008 12019
33. CoombesBK
2009 Type III secretion systems in symbiotic adaptation of pathogenic and non-pathogenic bacteria. Trends Microbiol 17 89 94
34. DaleC
PlagueGR
WangB
OchmanH
MoranNA
2002 Type III secretion systems and the evolution of mutualistic endosymbiosis. Proc Natl Acad Sci U S A 99 12397 12402
35. ShimadaT
IshihamaA
BusbySJ
GraingerDC
2008 The Escherichia coli RutR transcription factor binds at targets within genes as well as intergenic regions. Nucleic Acids Res 36 3950 3955
36. ChoBK
KnightEM
BarrettCL
PalssonBO
2008 Genome-wide analysis of Fis binding in Escherichia coli indicates a causative role for A-/AT-tracts. Genome Res 18 900 910
37. MacArthurS
BrookfieldJF
2004 Expected rates and modes of evolution of enhancer sequences. Mol Biol Evol 21 1064 1073
38. SalcedoSP
HoldenDW
2003 SseG, a virulence protein that targets Salmonella to the Golgi network. EMBO J 22 5003 5014
39. DeiwickJ
SalcedoSP
BoucrotE
GillilandSM
HenryT
2006 The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche. Infect Immun 74 6965 6972
40. ShinD
LeeEJ
HuangH
GroismanEA
2006 A positive feedback loop promotes transcription surge that jump-starts Salmonella virulence circuit. Science 314 1607 1609
41. LangilleMG
BrinkmanFS
2009 IslandViewer: an integrated interface for computational identification and visualization of genomic islands. Bioinformatics 25 664 665
42. CrooksGE
HonG
ChandoniaJM
BrennerSE
2004 WebLogo: a sequence logo generator. Genome Res 14 1188 1190
43. UzzauS
Figueroa-BossiN
RubinoS
BossiL
2001 Epitope tagging of chromosomal genes in Salmonella. Proc Natl Acad Sci U S A 98 15264 15269
44. KrzywinskiM
ScheinJ
BirolI
ConnorsJ
GascoyneR
2009 Circos: an information aesthetic for comparative genomics. Genome Res 19 1639 1645
45. ThijsG
LescotM
MarchalK
RombautsS
De MoorB
2001 A higher-order background model improves the detection of promoter regulatory elements by Gibbs sampling. Bioinformatics 17 1113 1122
46. ThijsG
MarchalK
LescotM
RombautsS
De MoorB
2002 A Gibbs sampling method to detect overrepresented motifs in the upstream regions of coexpressed genes. J Comput Biol 9 447 464
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