Postdoc, Washington University, St Louis
Ph.D., University of Texas, Austin
B.S., University of Athens, Greece
Tel.: 909-869-4461 (office), 909-869-5080 (lab); Fax: 909-869-4078
Email: stathopoulos@csupomona.edu
Office: 4-3-545; Lab: 4-3-541
Lab web site
Biological Sciences Department, California State Polytechnic University
3801 West Temple Avenue, Pomona, CA 91768, USA
The growing number of complete bacterial genome sequences provides a powerful tool for studying the biology of bacteria and the diseases they cause in humans and animals. Genomics and modern experimental approaches to identify virulence factors and probe pathogen-host interactions have revolutionized the field of bacterial pathogenesis, the study of the molecular and cellular basis of bacterial diseases, and provide essential information for the development of new antibiotics and vaccines.
We have a strong interest in understanding how secreted proteins in bacteria are sorted, post-translationally modified, and exported across the bacterial membranes. Gram-negative bacteria have evolved various mechanisms to export proteins from the cytoplasm, where protein synthesis occurs, to the extracellular environment where their activity is required. Our research focuses on the autotransporter or Type V secretion, one of the sec-dependent pathways. The autotransporters (ATs) are multidomain proteins consisting of an N-terminal signal sequence, a passenger region to be delivered to the extracellular environment, and a conserved C-terminal domain that remains associated with the outer membrane. The C-terminal region is believed to adopt a beta-barrel conformation, forming a pore through the membrane and thus allowing translocation of the secreted protein to the extracellular environment. Then, the protein may either be cleaved and released or stay associated with the outer membrane. It has become apparent that many virulence factors, including extracellular toxins, nonpilus adhesins, invasions, and proteases, are secreted by the autotransporter pathway. Therefore an improved understanding of how these virulence factors are secreted, processed, and activated by the bacterial cell may provide us with new tools to develop new antibiotics, therapeutics, and vaccines to prevent and treat bacterial diseases.
Unlike traditional vaccines that were based on the use of a purified antigen or an inactivated, killed form of the pathogen, live recombinant vaccines consist of an avirulent live bacterial or viral carrier expressing foreign antigens--antigens derived from a different pathogenic microorganism. Bacteria are attractive candidates as carriers of foreign antigens in live recombinant vaccines because they are often strongly immunogenic, can persist for long time by colonizing host tissues, and can express more than one different foreign antigen. Salmonella is genetically one of the best-characterized organisms used as a recombinant bacterial vaccine vector. In our studies, we use engineered Salmonella vaccine carriers with the balanced-lethal Asd system that ensures the stability and efficient delivery of foreign antigens under in-vivo conditions. Our main goal is to develop new antigen delivery technologies that could enhance the efficacy of existing live recombinant vaccines. As infectious diseases continue to be a leading cause of morbidity and mortality worldwide, recombinant live vaccines become a promising biotechnological tool with the potential to prevent the spread of new, emerging pathogens and the resurgence of the old ones.
Schematic Presentation of Secretion Pathways in Gram-negative Bacteria
(from J Bacteriol. 187:4306, 2005). (Click to enlarge)
C Stathopoulos, YT Yen, C Tsang, & T Cameron. 2007. Protein secretion in the prokaryotic cell. In “Bacterial Physiology: A Molecular Approach”. Ed.: W. Elsharoud. Chapter 5. Springer.
YT Yen & C Stathopoulos. 2007. Identification of autotransporters secreted by the type V secretion systems in bacterial genomes. Methods Mol. Biol., in press.
YT Yen, A Karkal, M Bhattacharya, RC Fernandez, & C Stathopoulos. 2007. Identification and characterization of autotransporter proteins of Yersinia pestis KIM. Mol. Membr. Biol., 24:28-40.
M Kostakioti & C Stathopoulos. 2006. Role of the a-helical linker of the C-terminal translocator on the biogenesis of the Serine Protease Subfamily of autotransporters. Infect. Immun, 74:4961-4969.
V Hritonenko, M Kostakioti, & C Stathopoulos. 2006. Quaternary structure of a SPATE autotransporter. Mol. Membr. Biol., 23:466-474.
M Kostakioti & C Stathopoulos. 2004. Functional analysis of the Tsh autotransporter of an avian pathogenic Escherichia coli strain. Infect. Immun., 72:5548-5554.
CL Newman & C Stathopoulos. 2004. Autotransporter and Two-partner secretion: Delivery of large-size virulence factors by gram-negative bacterial pathogens. Crit. Reviews Microbiol., 30:275-286.
DG Thanassi, C Stathopoulos, K Dodgon, D Geiger, & SJ Hultgren. 2002. Bacterial outer membrane ushers contain distinct targeting and assembly domains for pilus biogenesis. J. Bacteriol. 184:6260-6269.
C Stathopoulos, DR Hendrixson, DG Thanassi, SJ Hultgren, JW St. Geme III, & R Curtiss III. 2000. Secretion of virulence determinants by the general secretory pathway in Gram-negative pathogens: An evolving story. Microbes & Infect. 2:1061-1072.
C Stathopoulos, D Provence, & R Curtiss III. 1999. Characterization of the avian pathogenic Escherichia coli hemagglutinin Tsh, a member of the immunoglobulin A protease-type family of autotransporters. Infect. Immun. 67:772-781.
PN Meyer, MR Wilmes-Riesenberg, C Stathopoulos, & R Curtiss III. 1998. Virulence of a Salmonella typhimurium OmpD mutant. Infect. Immun. 66:387-390.
G Georgiou, C Stathopoulos, PS Daugherty, AR Nayak, BL Iverson, & R Curtiss III. 1997. Display of heterologous proteins on the surface of microorganisms: From the screening of combinatorial libraries to live recombinant vaccines. Nature Biotechnol. 15:1-7.
DR Hendrixson., ML de la Morena, C Stathopoulos, & JW St Geme III. 1997. Structural determinants of processing and secretion of the Haemophilus influenzae Hap protein. Mol. Microbiol. 26:505-518.
2007 Provost’s Teacher-Scholar Award, Cal Poly Pomona
2007 Chair’s Fund Travel Award, Gordon Research Conference
2007 Travel Grant, California State University Program for Education and Research in Biotechnology (CSUPERB)
2006 Mini-grant Program Award, Faculty Center for Professional Development, Cal Poly Pomona
2006 Research, Scholarship, & Creative Activity Program Award (RSCA), University Research Council, Cal Poly Pomona
2006 Presidential Travel Fund Award, Cal Poly Pomona
Yihfen T. Yen (Lecturer/Research Scientist)
Casey Tsang (MS student)
Todd Cameron (Undergraduate student)
Victoria Hritonenko (PhD student)
Maria Kostakioti (PhD); currently a Postdoc with Prof. Scott Hultgren, Washington University
Aarthi Karkal (MS); currently a Research Associate at Baylor College of Medicine
Mou Bhattacharya (PhD)
Yuejin Li (Postdoc)
Edmund Ho (Lab tech)
Cheryl L. Newman (MS)
