Skip redundant pieces
CLAS : Biological Sciences : Department of Molecular Biosciences

Faculty

P. Scott Hefty
Ph.D., University of Oklahoma Health Sciences Center, 2001
Assistant Professor
8051 Haworth
Phone: (785) 864-5392; email:

P. Scott HeftyChlamydiae include successful human pathogens that have an immense impact on public health. Chlamydia trachomatis is the most common sexually transmitted bacterial infection world-wide with an estimated 90 million new cases annually. In developing countries, C. trachomatis is the leading cause of preventable blindness. Additionally, growing evidence supports C. pneumoniae as a contributing factor of atherosclerosis and coronary disease, the second leading cause of human mortality. Despite its medical significance, many fundamental questions of chlamydial biology have yet to be elucidated, especially those related to developmental regulation and pathogenesis.

Chlamydiae are obligate intracellular bacteria that are perpetuated by a defining biphasic developmental cycle that is inexorably linked to pathogenesis. Intercellular transmission of Chlamydia occurs as a metabolically inert elementary body (EB) that, subsequent to gaining entry to the host cell, converts into a metabolically active, yet non-infectious, reticulate body (RB). Following numerous rounds of replication, reciprocal conversion occurs and the developmental cycle is repeated as EBs are released into the extracellular milieu. An important deviation from this cycle, especially clinically, is establishment of a persistent infection where RB to EB conversion is arrested. Relatively little information exists regarding specific extrinsic or intrinsic factors that regulate the developmental cycle and persistence. Moreover, the detailed events that occur during conversion processes are equally unknown.

Defining regulatory components of chlamydial development will provide critical insight to basic biology and mechanisms of pathogenesis. Our global transcriptional analysis of the developmental cycle revealed that virtually all genes differentially expressed are up-regulated during the developmental stage correlated with RB to EB conversion. This highlights the governing role of transcriptional regulation during this essential developmental stage. EBs exhibit extensive infectious capabilities as they bind, facilitate entry and establish a unique non-lysosomal vacuole requisite for chlamydial growth. Furthermore, induction of persistent infections results in RB to EB conversion arrest. Therefore, a research goal is to elucidate and characterize regulatory mechanisms of gene expression during chlamydial RB to EB conversion. Currently, research is focused on elucidating the role of an alternative sigma factor, s28, a transcriptional activator, ChxR, and the regulatory mechanisms for the type III secretion system during the developmental cycle.

Representative Publications

  • Hefty, P. S. and R. S. Stephens (2007). "Chlamydial type III secretion system is encoded on ten operons preceded by sigma 70-like promoter elements." J Bacteriol 189(1): 198–206.
  • Koo, I. C., D. Walthers, P. S. Hefty, L. J. Kenney and R. S. Stephens (2006). "ChxR is a transcriptional activator in Chlamydia." Proc Natl Acad Sci U S A.
  • Hua, L., P. S. Hefty, Y. J. Lee, Y. M. Lee, R. S. Stephens and C. W. Price (2006). "Core of the partner switching signaling mechanism is conserved in the obligate intracellular pathogen, Chlamydia trachomatis." Mol Microbiol 59 (2): 623–36.
  • Hefty, P. S. and R. S. Stephens (2006). "Sigma 28 regulates expression of a tail-specific protease in Chlamydia." Proc. Int'l. Symp. on Hum. Chlamydial Inf. 11: 25–28
  • Alitalo, A., T. Meri, T. Chen, H. Lankinen, Z. Z. Cheng, T. S. Jokiranta, I. J. Seppala, P. Lahdenne, P. S. Hefty, D. R. Akins and S. Meri (2004). "Lysine-dependent multipoint binding of the Borrelia burgdorferi virulence factor outer surface protein E to the C terminus of factor H." J Immunol 172(10): 6195–201.
  • Brooks, C. S., P. S. Hefty, S. E. Jolliff and D. R. Akins (2003). "Global analysis of Borrelia burgdorferi genes regulated by mammalian host-specific signals." Infect Immun 71(6): 3371–83.
  • Alitalo, A., T. Meri, H. Lankinen, I. Seppala, P. Lahdenne, P. S. Hefty, D. Akins and S. Meri (2002). "Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs." J Immunol 169(7): 3847–53.
  • Hefty, P. S., C. S. Brooks, A. M. Jett, G. L. White, S. K. Wikel, R. C. Kennedy and D. R. Akins (2002). "OspE-related, OspF-related, and Elp lipoproteins are immunogenic in baboons experimentally infected with Borrelia burgdorferi and in human Lyme disease patients." J Clin Microbiol 40 (11): 4256–65.
  • Hefty, P. S., S. E. Jolliff, M. J. Caimano, S. K. Wikel and D. R. Akins (2002). "Changes in temporal and spatial patterns of outer surface lipoprotein expression generate population heterogeneity and antigenic diversity in the Lyme disease spirochete, Borrelia burgdorferi." Infect Immun 70 (7): 3468–78.
  • Hefty, P. S., S. E. Jolliff, M. J. Caimano, S. K. Wikel, J. D. Radolf and D. R. Akins (2001). "Regulation of OspE-related, OspF-related, and Elp lipoproteins of Borrelia burgdorferi strain 297 by mammalian host-specific signals." Infect Immun 69 (6): 3618–27.
  • Hefty, P. S. and R. C. Kennedy (1999). "Immunoglobulin variable regions as idiotype vaccines." Infect Dis Clin North Am 13 (1): 27–37, vi.
  • Watts, A. M., J. R. Stanley, M. H. Shearer, P. S. Hefty and R. C. Kennedy (1999). "Fetal immunization of baboons induces a fetal-specific antibody response." Nat Med 5(4): 427–30.