Research Summary

My research focuses on exploring the molecular mechanisms of pathogenesis in the foodborne human pathogen Campylobacter jejuni. C. jejuni is the leading worldwide cause of bacterial food poisoning; however, we know very little about how it causes disease, particularly in comparison to other pathogens such as E. coli and Salmonella.

C. jejuni interacts closely with intestinal epithelial cells during infection, causes marked inflammation, and the bacteria can both invade and translocate through the intestinal epithelium. One focus of my research is to identify and characterize C. jejuni genes involved in the intimate bacterium-host cell interaction, utilizing several new genomic and genetic tools developed in my laboratory. Using DNA microarrays, I identified several sets of C. jejuni genes whose expression was affected by close contact with human intestinal cells. We subsequently found that one of the up-regulated genes controls the C. jejuni stringent response, a general stress response that we found is required for C. jejuni to invade and survive inside epithelial cells. Ongoing projects are aimed at expanding our characterization of this new virulence determinant, exploring how the C. jejuni stringent response is regulated, and characterizing other bacterial factors that intersect with this response. Studies to explore other genes identified in the microarray screen are also planned.

We are also interested in understanding several specific regulatory elements that are likely to be involved in C. jejuni pathogenesis and colonization. We have already identified and characterized a novel two-component signal transduction system that appears to be specifically required for in vivo colonization; we are additionally exploring another two-component system that was up-regulated in the presence of host cells. Future work will focus on identifying the genes regulated by each of these systems and how they contribute to the bacteria’s ability to colonize and cause disease.

Finally, two longer-term goals of my research center on trying to understand how C. jejuni can live harmlessly as a commensal in most animal species yet causes severe disease in humans, and how a specific host or transmission environment contributes to pathogenicity. We have already determined that laboratory passage in a high O2 environment compromises the ability of C. jejuni to colonize its natural zoonotic hosts. Future work is aimed at (a) exploring how C. jejuni genotypes and genome evolution contribute to the successful colonization of specific host systems, and (b) investigating host cell responses to C. jejuni infection.

Bio

B.A. (1990) and Ph.D. (1997), University of California San Diego
Postdoctoral fellow (1998-2003), Stanford University

Publications
  1. Cameron, A., and Gaynor, E.C. (2014). “Hygromycin B and Apramycin antibiotic resistance cassettes for use in Campylobacter jejuni”. PLoS One 9(4):e95084. doi: 10.1371
  2. Frirdich E., Vermeulen J., Biboy J., Soares F., Taveirne M.E., Johnson J.G., DiRita V.J., Girardin S.E., Vollmer W., and Gaynor E.C. (2014). “Peptidoglycan LD-carboxypeptidase Pgp2 influences Campylobacter jejuni helical cell shape and pathogenic properties, and provides the substrate for the DL-carboxypeptidase Pgp1”. J Biol. Chem. 289(12):8007-18
  3. Frirdich, E., and Gaynor, E.C. (2013). “Peptidoglycan hydrolases, bacterial shape, and pathogenesis”. Current Opinion in Microbiology 16:1-12
  4. Cameron, A., Frirdich, E., Huynh, S., Parker, C.T., and Gaynor, E.C. (2012). “Hyperosmotic stress response of Campylobacter jejuni”. J Bacteriol. 194(22):6116-30
  5. Pryjma, M., Apel, D., Huynh, S., Parker, C.T., and Gaynor, E.C. (2012). “FdhTU-modulated formate dehydrogenase expression and electron donor availability enhance recovery of Campylobacter jejuni following host cell infection”. J Bacteriol. 194(15):3803-13
  6. Frirdich, E., Biboy, J., Adams, C., Lee, J., Ellermeier, J., Davis Gielda, L., DiRita, V.J., Girardin, S.E., Vollmer, W., and Gaynor, E.C. (2012). “Peptidoglycan-modifying enzyme Pgp1 is required for helical cell shape and pathogenicity traits in Campylobacter jejuni”. PLoS Path. 8(3): e1002602, doi: 10.1371/journal.ppat.1002602
  7. Szymanski, C.M. and Gaynor, E.C. (2012). “How a sugary bug gets through the day: recent developments in understanding fundamental processes impacting Campylobacter jejuni pathogenesis” Gut Microbes Special Issue on Enteric Pathogens, Mar 1;3(2):135-44
  8. Gaynor, E.C. and Szymanski, C.M. (2012). “The 30th Anniversary of Campylobacter, Helicobacter and Related Organisms Workshops – What Have We Learned in Three Decades?” Frontiers in Cellular and Infection Microbiology, doi: 10.3389/fcimb.2012.00020.
  9. Apel, D., Ellermeier, J., Pryjma, M., DiRita, V.J., and Gaynor, E.C. (2012). “Characterization of Campylobacter jejuni RacRS reveals roles in the heat shock response, motility, and maintenance of cell length homogeneity”. J Bacteriol. 194(9):2342-54
  10. Martinez-Gutierrez, F., Thi, E.P., Silverman, J.M., de Oliveira, C.C., Svensson, S.L., Vanden Hoek, A., Sanchez, E.M., Reiner, N.E., Gaynor, E.C., Pryzdial, E.L., Conway, E.M., Orrantia, E., Ruiz., F., Av-Gay, Y., and Bach, H. (2011). “Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles”. Nanomedicine 8(3):328-36.
  11. Li, X., Apel, D., Gaynor, E.C., and Tanner, M.E. (2011). “5-methylthioadenosine nucleosidase is implicated in playing a key role in a modified futalosine pathway for menaquinone biosynthesis in Campylobacter jejuni. J Biol Chem. 286(22):19392-8
  12. Chan, A.C., Doukov, T.I., Scofield, M., Tom-Yew, S.A., Ramin, A.B., Mackichan, J.K., Gaynor, E.C., and Murphy, M.E. (2010). “Structure and function of P19, a high-affinity iron transporter of the human pathogen Campylobacter jejuni. J Mol Biol. 401(4):590-604.
  13. Dalebroux, Z.D., Svensson, S.L., Gaynor, E.C., and Swanson, M.S. (2010). “ppGpp conjures bacterial virulence”. Microbiol Mol Biol Rev. 74(2):171-99. Review.
  14. Naito, M., Frirdich, E., Fields, J.A., Pryjma, M., Li, J., Cameron, A., Gilbert, M., Thompson, S.A., and Gaynor, E.C. (2010). “Effects of sequential Campylobacter jejuni 81-176 lipooligosaccharide core truncations on biofilm formation, stress survival, and pathogenesis”. J Bacteriol. 192(8):2182-92.
  15. Lin, A.E., Krastel, K., Hobb, R.I., Thompson, S.A., Cvitkovitch, D.G., and Gaynor, E.C. (2009). “Atypical roles for Campylobacter jejuni amino acid binding cassette transporter components PaqP and PaqQ in bacterial stress tolerance and pathogen-host cell dynamics”. Infect Immun. 77(11):4912-24.
  16. Svensson, S.L., Davis, L.M., MacKichan, J.K., Allan, B.J., Pajaniappan, M., Thompson, S.A., and Gaynor, E.C. (2009) “The CprS sensor kinase of the zoonotic pathogen Campylobacter jejuni influences biofilm formation and is required for optimal chick colonization”. Mol Microbiol. Jan; 71(1):253-72.
  17. Thompson, S.A., and Gaynor, E.C. (2008). “Campylobacter jejuni host tissue tropism: a consequence of its low-carb lifestyle?” Cell Host Microbe Nov; 13:4(5)409-10.
  18. Champion, O.L., Valdez, Y., Thorson, L., Guttman, J.A., Menendez, A., Gaynor, E.C., and Finlay, B.B. (2008) “A murine intra peritoneal infection model reveals that host resistance to Campylobacter jejuni is Nramp1 dependent”. Microbes Infect. July; 10(8):922-927.
  19. Svensson, S.L., Frirdich, E., and Gaynor, E.C. (2008) “Survival strategies of Campylobacter jejuni: stress responses, the viable but non-culturable state, and biofilms.” Invited book chapter for Campylobacter, Third Edition, C.M. Szymanski, I. Nachamkin, and M.J. Blaser, eds. (Herndon, VA: ASM Press), pp. 62–85.
  20. Pajaniappan, M., Cawthraw, S.A., Newell, D.G., Gaynor, E.C., Fields, J.A., Rathbun, K., Hall, J.E., Burns, C.M., Kelly, D.J., and Thompson, S.A.. (2008) “A temperature-regulated Campylobacter jejuni gluconate dehydrogenase is involved in respiration-dependent energy production and chicken colonization. Mol. Microbiol. 68(2):474-91.
  21. McLennan, M.K., Ringoir, D.D., Frirdich, E., Svensson, S.L., Wells, D.H. Jarrell, H., Szymanski, C.M., and Gaynor, E.C. (2007) “Campylobacter jejuni biofilms up-regulated in a stringent response mutant utilize a calcofluor white-reactive polysaccharide.” J Bacteriol., 90(3):1097-107.
  22. Candon, H.L., Allan, B.J., Fraley, C.D., and Gaynor, E.C. (2007) “Polyphosphate kinase 1 (PPK1) is a pathogenesis determinant in Campylobacter jejuni.” J Bacteriol. 189:8099-108.
  23. Lupp, C., Robertson, M.L., Wickham, M.E., Sekirov, I., Champion, O.L., Gaynor, E.C., and Finlay, B.B. (2007). “Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriacaea.” Cell Host and Microbe 2:204
  24. Mouery, K., Rader, B.A., Gaynor, E.C., and Guillemin, K. (2006) “The stringent response is required for Helicobacter pylori survival of stationary phase, exposure to acid, and aerobic shock.” J Bacteriol. 188:5494-500.
  25. Wells DH, Gaynor EC. Helicobacter pylori initiates the stringent response upon nutrient and pH downshift.
    J Bacteriol. 2006 May;188(10):3726-9.
  26. Gaynor EC, Wells DH, MacKichan JK, and Falkow S. The Campylobacter jejuni stringent response controls specific stress survival and virulence-associated phenotypes. Mol Microbiol. 2005 Apr;56(1):8-27.
  27. MacKichan JK, Gaynor EC, Chang C, Cawthraw S, Newell DG, Miller JF, and Falkow S. The Campylobacter jejuni dccRS two-component system is required for optimal in vivo colonization but is dispensable for in vitro growth. Mol Microbiol. 2004 Dec;54(5):1269-86.
  28. Gaynor, E.C., Cawthraw, S., Manning, G., MacKichan, J.K., Falkow, S., and Newell, D.G. (2004) The genome-sequenced variant of Campylobacter jejuni NCTC11168 and the original clonal clinical isolate differ markedly in colonization, gene expression, and virulence-associated phenotypes. J Bact 186:503-17.
  29. Leonard EE 2nd, Takata T, Blaser MJ, Falkow S, Tompkins LS, and Gaynor EC. Use of an open-reading frame-specific Campylobacter jejuni DNA microarray as a new genotyping tool for studying epidemiologically related isolates. J Infect Dis. 2003 Feb 15;187(4):691-4.
  30. Gaynor EC, Ghori N, and Falkow S. Bile-induced ‘pili’ in Campylobacter jejuni are bacteria-independent artifacts of the culture medium. Mol Microbiol. 2001 Mar;39(6):1546-9.
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