Genetic Interaction Maps in Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways


As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target.


Vyšlo v časopise: Genetic Interaction Maps in Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways. PLoS Genet 7(11): e32767. doi:10.1371/journal.pgen.1002377
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002377

Souhrn

As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target.


Zdroje

1. Díaz-MejíaJJBabuMEmiliA 2009 Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome. FEMS Microbiol Rev 33 66 97

2. NicholsRJSenSChooYJBeltraoPZietekM 2011 Phenotypic landscape of a bacterial cell. Cell 144 143 156

3. SilhavyTJKahneDWalkerS 2010 The bacterial cell envelope. Cold Spring Harb Perspect Biol 2 a000414

4. HaselbeckRWallDJiangBKetelaTZyskindJ 2002 Comprehensive essential gene identification as a platform for novel anti-infective drug discovery. Curr Pharm Des 8 1155 1172

5. FalconerSBBrownED 2009 New screens and targets in antibacterial drug discovery. Curr Opin Microbiol 12 497 504

6. BabuMGreenblattJFEmiliAStrynadkaNCReithmeierRA 2010 Structure of a SLC26 Anion Transporter STAS Domain in Complex with Acyl Carrier Protein: Implications for E. coli YchM in Fatty Acid Metabolism. Structure 18 1450 1462

7. ParkJTUeharaT 2008 How bacteria consume their own exoskeletons (turnover and recycling of cell wall peptidoglycan). Microbiol Mol Biol Rev 72 211 227

8. RuizNKahneDSilhavyTJ 2009 Transport of lipopolysaccharide across the cell envelope: the long road of discovery. Nat Rev Microbiol 7 677 683

9. KnowlesTJScott-TuckerAOverduinMHendersonIR 2009 Membrane protein architects: the role of the BAM complex in outer membrane protein assembly. Nat Rev Microbiol 7 206 214

10. RuizNGronenbergLSKahneDSilhavyTJ 2008 Identification of two inner-membrane proteins required for the transport of lipopolysaccharide to the outer membrane of Escherichia coli. Proc Natl Acad Sci U S A 105 5537 5542

11. SperandeoPVillaRMartoranaASamalikovaMGrandoriR 2010 New insights into the Lpt machinery for LPS transport to the cell surface: LptA-LptC interaction and LptA stability as a sensors of a properly assembled transenvelope complex. J Bacteriol In Press

12. TypasABanzhafMvan den Berg van SaparoeaBVerheulJBiboyJ 2010 Regulation of peptidoglycan synthesis by outer-membrane proteins. Cell 143 1097 1109

13. WuTMalinverniJRuizNKimSSilhavyTJ 2005 Identification of a multicomponent complex required for outer membrane biogenesis in Escherichia coli. Cell 121 235 245

14. HuPJangaSCBabuMDiaz-MejiaJJButlandG 2009 Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins. PLoS Biol 7 e1000096 doi:10.1371/journal.pbio.1000096

15. BabaTAraTHasegawaMTakaiYOkumuraY 2006 Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2 2006.0008

16. HartwellLHHopfieldJJLeiblerSMurrayAW 1999 From molecular to modular cell biology. Nature 402 C47 52

17. GirgisHSHottesAKTavazoieS 2009 Genetic architecture of intrinsic antibiotic susceptibility. PLoS ONE 4 e5629 doi:10.1371/journal.pone.0005629

18. DixonSJCostanzoMBaryshnikovaAAndrewsBBooneC 2009 Systematic mapping of genetic interaction networks. Annu Rev Genet 43 601 625

19. CostanzoMBaryshnikovaABellayJKimYSpearED 2010 The genetic landscape of a cell. Science 327 425 431

20. SchuldinerMCollinsSRThompsonNJDenicVBhamidipatiA 2005 Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell 123 507 519

21. BandyopadhyaySMehtaMKuoDSungMKChuangR 2010 Rewiring of genetic networks in response to DNA damage. Science 330 1385 1389

22. BabuMMussoGDiaz-MejiaJJButlandGGreenblattJF 2009 Systems-level approaches for identifying and analyzing genetic interaction networks in Escherichia coli and extensions to other prokaryotes. Mol Biosyst 12 1439 1455

23. ButlandGBabuMDíaz-MejíaJJBohdanaFPhanseS 2008 eSGA: E. coli synthetic genetic array analysis. Nat Methods 5 789 795

24. BeltraoPCagneyGKroganNJ 2010 Quantitative genetic interactions reveal biological modularity. Cell 141 739 745

25. BandyopadhyaySKelleyRKroganNJIdekerT 2008 Functional maps of protein complexes from quantitative genetic interaction data. PLoS Comput Biol 4 e1000065 doi:10.1371/journal.pcbi.1000065

26. RuizNFalconeBKahneDSilhavyTJ 2005 Chemical conditionality: a genetic strategy to probe organelle assembly. Cell 121 307 317

27. SklarJGWuTKahneDSilhavyTJ 2007 Defining the roles of the periplasmic chaperones SurA, Skp, and DegP in Escherichia coli. Genes Dev 21 2473 2484

28. EbersbachGGalliEMoller-JensenJLoweJGerdesK 2008 Novel coiled-coil cell division factor ZapB stimulates Z ring assembly and cell division. Mol Microbiol 68 720 735

29. PriceMNArkinAPAlmEJ 2006 The life-cycle of operons. PLoS Genet 2 e96 doi:10.1371/journal.pgen.0020096

30. FaithJJHayeteBThadenJTMognoIWierzbowskiJ 2007 Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLoS Biol 5 e8 doi:10.1371/journal.pbio.0050008

31. LamarcheMGKimSHCrepinSMourezMBertrandN 2008 Modulation of hexa-acyl pyrophosphate lipid A population under Escherichia coli phosphate (Pho) regulon activation. J Bacteriol 190 5256 5264

32. RowlandSLFuXSayedMAZhangYCookWR 2000 Membrane redistribution of the Escherichia coli MinD protein induced by MinE. J Bacteriol 182 613 619

33. HigashiKIshigureHDemizuRUemuraTNishinoK 2008 Identification of a spermidine excretion protein complex (MdtJI) in Escherichia coli. J Bacteriol 190 872 878

34. CorbinBDWangYBeuriaTKMargolinW 2007 Interaction between cell division proteins FtsE and FtsZ. J Bacteriol 189 3026 3035

35. WhitfieldC 2006 Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu Rev Biochem 75 39 68

36. HugIFeldmanMF 2010 Analogies and homologies in lipopolysaccharide and glycoprotein biosynthesis in bacteria. Glycobiology 21 138 151

37. MajdalaniNGottesmanS 2005 The Rcs phosphorelay: a complex signal transduction system. Annu Rev Microbiol 59 379 405

38. GottesmanSStoutV 1991 Regulation of capsular polysaccharide synthesis in Escherichia coli K12. Mol Microbiol 5 1599 1606

39. BergJMTymoczkoJLStryerL 2002 Protein Turnover and Amino Acid Catabolism New York W. H. Freeman 1100

40. CollinsSRMillerKMMaasNLRoguevAFillinghamJ 2007 Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map. Nature 446 806 810

41. TauraTItoK 1991 Does protein secretion activity vary during the cell cycle of Escherichia coli? J Biochem 109 811 815

42. OliverDBBeckwithJ 1981 E. coli mutant pleiotropically defective in the export of secreted proteins. Cell 25 765 772

43. ChungHSYaoZGoehringNWKishonyRBeckwithJ 2009 Rapid beta-lactam-induced lysis requires successful assembly of the cell division machinery. Proc Natl Acad Sci U S A 106 21872 21877

44. HeidrichCUrsinusABergerJSchwarzHHoltjeJV 2002 Effects of multiple deletions of murein hydrolases on viability, septum cleavage, and sensitivity to large toxic molecules in Escherichia coli. J Bacteriol 184 6093 6099

45. UeharaTDinhTBernhardtTG 2009 LytM-domain factors are required for daughter cell separation and rapid ampicillin-induced lysis in Escherichia coli. J Bacteriol 191 5094 5107

46. ChngSSRuizNChimalakondaGSilhavyTJKahneD 2010 Characterization of the two-protein complex in Escherichia coli responsible for lipopolysaccharide assembly at the outer membrane. Proc Natl Acad Sci U S A 107 5363 5368

47. VaaraMNurminenM 1999 Outer membrane permeability barrier in Escherichia coli mutants that are defective in the late acyltransferases of lipid A biosynthesis. Antimicrob Agents Chemother 43 1459 1462

48. MamatUMeredithTCAggarwalPKühlAKirchhoffP 2008 Single amino acid substitutions in either YhjD or MsbA confer viability to 3-deoxy-d-manno-oct-2-ulosonic acid-depleted Escherichia coli. Mol Microbiol 67 633 648

49. NaritaSTokudaH 2009 Biochemical characterization of an ABC transporter LptBFGC complex required for the outer membrane sorting of lipopolysaccharides. FEBS Lett 583 2160 2164

50. SperandeoPLauFKCarpentieriADe CastroCMolinaroA 2008 Functional analysis of the protein machinery required for transport of lipopolysaccharide to the outer membrane of Escherichia coli. J Bacteriol 190 4460 4469

51. VogelJPapenfortK 2006 Small non-coding RNAs and the bacterial outer membrane. Curr Opin Microbiol 9 605 611

52. EddySR 2001 Non-coding RNA genes and the modern RNA world. Nat Rev Genet 2 919 929

53. GeissmannTChevalierCCrosMJBoissetSFechterP 2009 A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation. Nucleic Acids Res 37 7239 7257

54. TjadenBGoodwinSSOpdykeJAGuillierMFuDX 2006 Target prediction for small, noncoding RNAs in bacteria. Nucleic Acids Res 34 2791 2802

55. SarseroJPWookeyPJPittardAJ 1991 Regulation of expression of the Escherichia coli K-12 mtr gene by TyrR protein and Trp repressor. J Bacteriol 173 4133 4143

56. PulvermacherSCStaufferLTStaufferGV 2009 Role of the sRNA GcvB in regulation of cycA in Escherichia coli. Microbiology 155 106 114

57. NoinajNGuillierMBarnardTJBuchananSK 2010 TonB-dependent transporters: regulation, structure, and function. Annu Rev Microbiol 64 43 60

58. TischlerJLehnerBFraserAG 2008 Evolutionary plasticity of genetic interaction networks. Nat Genet 40 390 391

59. SrinivasNJetterPUeberbacherBJWerneburgMZerbeK 2010 Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa. Science 327 1010 1013

60. TypasANicholsRJSiegeleDAShalesMCollinsSR 2008 High-throughput, quantitative analyses of genetic interactions in E. coli. Nat Methods 5 781 787

61. CollinsSRSchuldinerMKroganNJWeissmanJS 2006 A strategy for extracting and analyzing large-scale quantitative epistatic interaction data. Genome Biol 7 R63

62. Le MeurNGentlemanR 2008 Modeling synthetic lethality. Genome Biol 9 R135

63. BenjaminiYHochbergY 1995 Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc Ser B 57 589 300

64. MucksteinUTaferHHackermullerJBernhartSHStadlerPF 2006 Thermodynamics of RNA-RNA binding. Bioinformatics 22 1177 1182

65. KitagawaMAraTArifuzzamanMIoka-NakamichiTInamotoE 2005 Complete set of ORF clones of Escherichia coli ASKA library (a complete set of E. coli K-12 ORF archive): unique resources for biological research. DNA Res 12 291 299

66. BabuMButlandGPogoutseOLiJGreenblattJF 2009 Sequential peptide affinity purification system for the systematic isolation and identification of protein complexes from Escherichia coli. Methods Mol Biol 564 373 400

67. TranAXTrentMSWhitfieldC 2008 The LptA protein of Escherichia coli is a periplasmic lipid A-binding protein involved in the lipopolysaccharide export pathway. J Biol Chem 283 20342 20349

68. HuangKCMukhopadhyayRWenBGitaiZWingreenNS 2008 Cell shape and cell-wall organization in Gram-negative bacteria. Proc Natl Acad Sci U S A 105 19282 19287

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Genetika Reprodukčná medicína

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PLOS Genetics


2011 Číslo 11
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