Sean D. Crosson

Research Summary
We investigate the molecular basis of environmental adaptation in bacteria that inhabit niches ranging from freshwater, to the ocean, to the interior of mammalian cells. Our studies center on the class Alphaproteobacteria, including the freshwater bacterium Caulobacter crescentus, the marine anoxygenic photosynthetic bacterium Erythrobacter litoralis, and the intracellular pathogen Brucella abortus, which is a causative agent of the zoonotic disease, brucellosis. We utilize a cross-disciplinary set of experimental and computational approaches that have defined new mechanisms of cell adhesion control, nutrient sensing, and stress sensing, and have uncovered genes and signaling pathways required for maintenance of chronic Brucella infection.
Keywords
Microbiology, Signal Transduction Systems, Host-Pathogen Interactions, Freshwater Biology, Structural Biology, Biochemistry
Education
  • Stanford University, Stanford, CA, postdoc Microbiology 2005
  • The University of Chicago, Chicago, IL, PhD Biochemistry and Molecular Biophysics 2002
  • Earlham College, Richmond, IN, BA Biology 1996
Awards & Honors
  • 1995 - Phi Beta Kappa Earlham College
  • 1998 - 2001 National Science Foundation Graduate Research Fellowship University of Chicago
  • 2007 - Beckman Young Investigator, Arnold and Mabel Beckman Foundation University of Chicago
  • 2017 - Fellow, American Academy of Microbiology
Publications
  1. Reyes Ruiz LM, Fiebig A, Crosson S. Regulation of bacterial surface attachment by a network of sensory transduction proteins. PLoS Genet. 2019 May 10; 15(5):e1008022. View in: PubMed

  2. Herrou J, Willett JW, Fiebig A, Czyz DM, Cheng JX, Ultee E, Briegel A, Bigelow L, Babnigg G, Kim Y, Crosson S. Brucella periplasmic protein EipB is a molecular determinant of cell envelope integrity and virulence. J Bacteriol. 2019 Apr 01. View in: PubMed

  3. Hershey DM, Fiebig A, Crosson S. A Genome-Wide Analysis of Adhesion in Caulobacter crescentus Identifies New Regulatory and Biosynthetic Components for Holdfast Assembly. MBio. 2019 02 12; 10(1). View in: PubMed

  4. Herrou J, Willett JW, Fiebig A, Varesio LM, Czyz DM, Cheng JX, Ultee E, Briegel A, Bigelow L, Babnigg G, Kim Y, Crosson S. Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus. Mol Microbiol. 2019 Mar; 111(3):637-661. View in: PubMed

  5. Hentchel KL, Reyes Ruiz LM, Curtis PD, Fiebig A, Coleman ML, Crosson S. Genome-scale fitness profile of Caulobacter crescentus grown in natural freshwater. ISME J. 2019 02; 13(2):523-536. View in: PubMed

  6. Tien MZ, Stein BJ, Crosson S. Coherent Feedforward Regulation of Gene Expression by Caulobacter sT and GsrN during Hyperosmotic Stress. J Bacteriol. 2018 Oct 01; 200(19). View in: PubMed

  7. Tien M, Fiebig A, Crosson S. Gene network analysis identifies a central post-transcriptional regulator of cellular stress survival. Elife. 2018 03 14; 7. View in: PubMed

  8. Luebke JL, Eaton DS, Sachleben JR, Crosson S. Allosteric control of a bacterial stress response system by an anti-s factor. Mol Microbiol. 2018 01; 107(2):164-179. View in: PubMed

  9. Czyz DM, Willett JW, Crosson S. Brucella abortus Induces a Warburg Shift in Host Metabolism That Is Linked to Enhanced Intracellular Survival of the Pathogen. J Bacteriol. 2017 08 01; 199(15). View in: PubMed

  10. Herrou J, Crosson S, Fiebig A. Structure and function of HWE/HisKA2-family sensor histidine kinases. Curr Opin Microbiol. 2017 Apr; 36:47-54. View in: PubMed

  11. Herrou J, Willett JW, Czyz DM, Babnigg G, Kim Y, Crosson S. Conserved ABC Transport System Regulated by the General Stress Response Pathways of Alpha- and Gammaproteobacteria. J Bacteriol. 2017 03 01; 199(5). View in: PubMed

  12. Czyz DM, Jain-Gupta N, Shuman HA, Crosson S. A dual-targeting approach to inhibit Brucella abortus replication in human cells. Sci Rep. 2016 10 21; 6:35835. View in: PubMed

  13. Baric RS, Crosson S, Damania B, Miller SI, Rubin EJ. Next-Generation High-Throughput Functional Annotation of Microbial Genomes. MBio. 2016 10 04; 7(5). View in: PubMed

  14. Willett JW, Crosson S. Atypical modes of bacterial histidine kinase signaling. Mol Microbiol. 2017 01; 103(2):197-202. View in: PubMed

  15. Willett JW, Herrou J, Czyz DM, Cheng JX, Crosson S. Brucella abortus ?rpoE1 confers protective immunity against wild type challenge in a mouse model of brucellosis. Vaccine. 2016 09 30; 34(42):5073-5081. View in: PubMed

  16. Herrou J, Choi VM, Bubeck Wardenburg J, Crosson S. Activation Mechanism of the Bacteroides fragilis Cysteine Peptidase, Fragipain. Biochemistry. 2016 07 26; 55(29):4077-84. View in: PubMed

  17. Gourse RL, Crosson S. Classic Spotlight: Studies of the Stringent Response. J Bacteriol. 2016 06 15; 198(12):1710. View in: PubMed

  18. Choi VM, Herrou J, Hecht AL, Teoh WP, Turner JR, Crosson S, Bubeck Wardenburg J. Activation of Bacteroides fragilis toxin by a novel bacterial protease contributes to anaerobic sepsis in mice. Nat Med. 2016 05; 22(5):563-7. View in: PubMed

  19. Eaton DS, Crosson S, Fiebig A. Proper Control of Caulobacter crescentus Cell Surface Adhesion Requires the General Protein Chaperone DnaK. J Bacteriol. 2016 10 01; 198(19):2631-42. View in: PubMed

  20. Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, Chang CI, Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferré-D'Amaré AR, Fromme JC, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P. Data publication with the structural biology data grid supports live analysis. Nat Commun. 2016 Mar 07; 7:10882. View in: PubMed

  21. Herrou J, Czyz DM, Willett JW, Kim HS, Chhor G, Babnigg G, Kim Y, Crosson S. WrpA Is an Atypical Flavodoxin Family Protein under Regulatory Control of the Brucella abortus General Stress Response System. J Bacteriol. 2016 Apr; 198(8):1281-93. View in: PubMed

  22. De Bolle X, Crosson S, Matroule JY, Letesson JJ. Brucella abortus Cell Cycle and Infection Are Coordinated. Trends Microbiol. 2015 Dec; 23(12):812-821. View in: PubMed

  23. Lubin EA, Henry JT, Fiebig A, Crosson S, Laub MT. Identification of the PhoB Regulon and Role of PhoU in the Phosphate Starvation Response of Caulobacter crescentus. J Bacteriol. 2016 01 01; 198(1):187-200. View in: PubMed

  24. Aakre CD, Herrou J, Phung TN, Perchuk BS, Crosson S, Laub MT. Evolving new protein-protein interaction specificity through promiscuous intermediates. Cell. 2015 Oct 22; 163(3):594-606. View in: PubMed

  25. Fiebig A, Herrou J, Willett J, Crosson S. General Stress Signaling in the Alphaproteobacteria. Annu Rev Genet. 2015; 49:603-25. View in: PubMed

  26. Herrou J, Willett JW, Crosson S. Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-s Factor. MBio. 2015 Jul 28; 6(4):e00910. View in: PubMed

  27. Willett JW, Herrou J, Briegel A, Rotskoff G, Crosson S. Structural asymmetry in a conserved signaling system that regulates division, replication, and virulence of an intracellular pathogen. Proc Natl Acad Sci U S A. 2015 Jul 14; 112(28):E3709-18. View in: PubMed

  28. Wright CS, Banerjee S, Iyer-Biswas S, Crosson S, Dinner AR, Scherer NF. Intergenerational continuity of cell shape dynamics in Caulobacter crescentus. Sci Rep. 2015 Mar 17; 5:9155. View in: PubMed

  29. Dupré E, Herrou J, Lensink MF, Wintjens R, Vagin A, Lebedev A, Crosson S, Villeret V, Locht C, Antoine R, Jacob-Dubuisson F. Virulence regulation with Venus flytrap domains: structure and function of the periplasmic moiety of the sensor-kinase BvgS. PLoS Pathog. 2015 Mar; 11(3):e1004700. View in: PubMed

  30. Iyer-Biswas S, Wright CS, Henry JT, Lo K, Burov S, Lin Y, Crooks GE, Crosson S, Dinner AR, Scherer NF. Scaling laws governing stochastic growth and division of single bacterial cells. Proc Natl Acad Sci U S A. 2014 Nov 11; 111(45):15912-7. View in: PubMed

  31. Kim HS, Willett JW, Jain-Gupta N, Fiebig A, Crosson S. The Brucella abortus virulence regulator, LovhK, is a sensor kinase in the general stress response signalling pathway. Mol Microbiol. 2014 Nov; 94(4):913-25. View in: PubMed

  32. Marek G, Pannu V, Shanmugham P, Pancione B, Mascia D, Crosson S, Ishimoto T, Sautin YY. Adiponectin resistance and proinflammatory changes in the visceral adipose tissue induced by fructose consumption via ketohexokinase-dependent pathway. Diabetes. 2015 Feb; 64(2):508-18. View in: PubMed

  33. Schrader JM, Zhou B, Li GW, Lasker K, Childers WS, Williams B, Long T, Crosson S, McAdams HH, Weissman JS, Shapiro L. The coding and noncoding architecture of the Caulobacter crescentus genome. PLoS Genet. 2014 Jul; 10(7):e1004463. View in: PubMed

  34. Czyz DM, Potluri LP, Jain-Gupta N, Riley SP, Martinez JJ, Steck TL, Crosson S, Shuman HA, Gabay JE. Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens. MBio. 2014 Jul 29; 5(4):e01534-14. View in: PubMed

  35. Fiebig A, Herrou J, Fumeaux C, Radhakrishnan SK, Viollier PH, Crosson S. A cell cycle and nutritional checkpoint controlling bacterial surface adhesion. PLoS Genet. 2014 Jan; 10(1):e1004101. View in: PubMed

  36. Herrou J, Crosson S. Molecular structure of the Brucella abortus metalloprotein RicA, a Rab2-binding virulence effector. Biochemistry. 2013 Dec 17; 52(50):9020-8. View in: PubMed

  37. Henry JT, Crosson S. Chromosome replication and segregation govern the biogenesis and inheritance of inorganic polyphosphate granules. Mol Biol Cell. 2013 Oct; 24(20):3177-86. View in: PubMed

  38. Kim HS, Caswell CC, Foreman R, Roop RM, Crosson S. The Brucella abortus general stress response system regulates chronic mammalian infection and is controlled by phosphorylation and proteolysis. J Biol Chem. 2013 May 10; 288(19):13906-16. View in: PubMed

  39. Herrou J, Crosson S. myo-inositol and D-ribose ligand discrimination in an ABC periplasmic binding protein. J Bacteriol. 2013 May; 195(10):2379-88. View in: PubMed

  40. Boutte CC, Crosson S. Bacterial lifestyle shapes stringent response activation. Trends Microbiol. 2013 Apr; 21(4):174-80. View in: PubMed

  41. Lin Y, Li Y, Crosson S, Dinner AR, Scherer NF. Phase resetting reveals network dynamics underlying a bacterial cell cycle. PLoS Comput Biol. 2012; 8(11):e1002778. View in: PubMed

  42. Herrou J, Rotskoff G, Luo Y, Roux B, Crosson S. Structural basis of a protein partner switch that regulates the general stress response of a-proteobacteria. Proc Natl Acad Sci U S A. 2012 May 22; 109(21):E1415-23. View in: PubMed

  43. Foreman R, Fiebig A, Crosson S. The LovK-LovR two-component system is a regulator of the general stress pathway in Caulobacter crescentus. J Bacteriol. 2012 Jun; 194(12):3038-49. View in: PubMed

  44. Heaton BE, Herrou J, Blackwell AE, Wysocki VH, Crosson S. Molecular structure and function of the novel BrnT/BrnA toxin-antitoxin system of Brucella abortus. J Biol Chem. 2012 Apr 06; 287(15):12098-110. View in: PubMed

  45. Boutte CC, Henry JT, Crosson S. ppGpp and polyphosphate modulate cell cycle progression in Caulobacter crescentus. J Bacteriol. 2012 Jan; 194(1):28-35. View in: PubMed

  46. Herrou J, Crosson S. Function, structure and mechanism of bacterial photosensory LOV proteins. Nat Rev Microbiol. 2011 Aug 08; 9(10):713-23. View in: PubMed

  47. Henry JT, Crosson S. Ligand-binding PAS domains in a genomic, cellular, and structural context. Annu Rev Microbiol. 2011; 65:261-86. View in: PubMed

  48. Alexandre G, Crosson S, Shimizu T, Msadek T. Bacterial moving and shaking: the 11th blast meeting. Mol Microbiol. 2011 Jul; 81(1):8-22. View in: PubMed

  49. Boutte CC, Crosson S. The complex logic of stringent response regulation in Caulobacter crescentus: starvation signalling in an oligotrophic environment. Mol Microbiol. 2011 May; 80(3):695-714. View in: PubMed

  50. van Stokkum IH, Gauden M, Crosson S, van Grondelle R, Moffat K, Kennis JT. The primary photophysics of the Avena sativa phototropin 1 LOV2 domain observed with time-resolved emission spectroscopy. Photochem Photobiol. 2011 May-Jun; 87(3):534-41. View in: PubMed

  51. Lin Y, Crosson S, Scherer NF. Single-gene tuning of Caulobacter cell cycle period and noise, swarming motility, and surface adhesion. Mol Syst Biol. 2010 Dec 21; 6:445. View in: PubMed

  52. Herrou J, Foreman R, Fiebig A, Crosson S. A structural model of anti-anti-s inhibition by a two-component receiver domain: the PhyR stress response regulator. Mol Microbiol. 2010 Oct; 78(2):290-304. View in: PubMed

  53. Purcell EB, McDonald CA, Palfey BA, Crosson S. An analysis of the solution structure and signaling mechanism of LovK, a sensor histidine kinase integrating light and redox signals. Biochemistry. 2010 Aug 10; 49(31):6761-70. View in: PubMed

  54. Fiebig A, Castro Rojas CM, Siegal-Gaskins D, Crosson S. Interaction specificity, toxicity and regulation of a paralogous set of ParE/RelE-family toxin-antitoxin systems. Mol Microbiol. 2010 Jul 01; 77(1):236-51. View in: PubMed

  55. Marks ME, Castro-Rojas CM, Teiling C, Du L, Kapatral V, Walunas TL, Crosson S. The genetic basis of laboratory adaptation in Caulobacter crescentus. J Bacteriol. 2010 Jul; 192(14):3678-88. View in: PubMed

  56. Alexandre MT, Purcell EB, van Grondelle R, Robert B, Kennis JT, Crosson S. Electronic and protein structural dynamics of a photosensory histidine kinase. Biochemistry. 2010 Jun 15; 49(23):4752-9. View in: PubMed

  57. Dalton KM, Crosson S. A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex. Biochemistry. 2010 Mar 16; 49(10):2205-15. View in: PubMed

  58. Idnurm A, Crosson S. The photobiology of microbial pathogenesis. PLoS Pathog. 2009 Nov; 5(11):e1000470. View in: PubMed

  59. Siegal-Gaskins D, Ash JN, Crosson S. Model-based deconvolution of cell cycle time-series data reveals gene expression details at high resolution. PLoS Comput Biol. 2009 Aug; 5(8):e1000460. View in: PubMed

  60. Boutte CC, Srinivasan BS, Flannick JA, Novak AF, Martens AT, Batzoglou S, Viollier PH, Crosson S. Genetic and computational identification of a conserved bacterial metabolic module. PLoS Genet. 2008 Dec; 4(12):e1000310. View in: PubMed

  61. Purcell EB, Boutte CC, Crosson S. Two-component signaling systems and cell cycle control in Caulobacter crescentus. Adv Exp Med Biol. 2008; 631:122-30. View in: PubMed

  62. Siegal-Gaskins D, Crosson S. Tightly regulated and heritable division control in single bacterial cells. Biophys J. 2008 Aug; 95(4):2063-72. View in: PubMed

  63. Purcell EB, Crosson S. Photoregulation in prokaryotes. Curr Opin Microbiol. 2008 Apr; 11(2):168-78. View in: PubMed

  64. Purcell EB, Siegal-Gaskins D, Rawling DC, Fiebig A, Crosson S. A photosensory two-component system regulates bacterial cell attachment. Proc Natl Acad Sci U S A. 2007 Nov 13; 104(46):18241-6. View in: PubMed

  65. Kennis JT, Crosson S. Microbiology. A bacterial pathogen sees the light. Science. 2007 Aug 24; 317(5841):1041-2. View in: PubMed

  66. Srajer V, Crosson S, Schmidt M, Key J, Schotte F, Anderson S, Perman B, Ren Z, Teng TY, Bourgeois D, Wulff M, Moffat K. Extraction of accurate structure-factor amplitudes from Laue data: wavelength normalization with wiggler and undulator X-ray sources. J Synchrotron Radiat. 2000 Jul 01; 7(Pt 4):236-44. View in: PubMed

  67. Crosson S, McGrath PT, Stephens C, McAdams HH, Shapiro L. Conserved modular design of an oxygen sensory/signaling network with species-specific output. Proc Natl Acad Sci U S A. 2005 May 31; 102(22):8018-23. View in: PubMed

  68. Crosson S, McAdams H, Shapiro L. A genetic oscillator and the regulation of cell cycle progression in Caulobacter crescentus. Cell Cycle. 2004 Oct; 3(10):1252-4. View in: PubMed

  69. Anderson S, Crosson S, Moffat K. Short hydrogen bonds in photoactive yellow protein. Acta Crystallogr D Biol Crystallogr. 2004 Jun; 60(Pt 6):1008-16. View in: PubMed

  70. Kennis JT, van Stokkum IH, Crosson S, Gauden M, Moffat K, van Grondelle R. The LOV2 domain of phototropin: a reversible photochromic switch. J Am Chem Soc. 2004 Apr 14; 126(14):4512-3. View in: PubMed

  71. Kennis JT, Crosson S, Gauden M, van Stokkum IH, Moffat K, van Grondelle R. Primary reactions of the LOV2 domain of phototropin, a plant blue-light photoreceptor. Biochemistry. 2003 Apr 01; 42(12):3385-92. View in: PubMed

  72. Crosson S, Rajagopal S, Moffat K. The LOV domain family: photoresponsive signaling modules coupled to diverse output domains. Biochemistry. 2003 Jan 14; 42(1):2-10. View in: PubMed

  73. Crosson S, Moffat K. Photoexcited structure of a plant photoreceptor domain reveals a light-driven molecular switch. Plant Cell. 2002 May; 14(5):1067-75. View in: PubMed

  74. Crosson S, Moffat K. Structure of a flavin-binding plant photoreceptor domain: insights into light-mediated signal transduction. Proc Natl Acad Sci U S A. 2001 Mar 13; 98(6):2995-3000. View in: PubMed