Arturo Centurion, MD
- Research Associate Professor, Division of Allergy and Infectious Diseases
- Adjunct Research Professor, Department of Global Health
- University of Washington
- Affiliate Investigator, Universidad Peruana Cayetano Heredia, Peru
Dr. Centurion's research focuses on Treponema pallidum, the etiologic agent of syphilis.
- Transcription Factors
Tight regulation of expression of virulence factors is key for bacterial pathogens. We have experimentally characterized the first transcription factor in the syphilis spirochete (Tp0262, a CRP homolog). In E coli, CRP regulates expression of more than 100 genes including several virulence factors. We have determined that Tp0262 activates or represses promoter activity in several tpr genes. Currently, in collaboration with Dr. Oleg Denisenko (Dept of Medicine), we are identifying the members of the CRP regulon in the syphilis spirochete using chromatin immunoprecipitation (CHIP) analysis and RNA sequencing.
- Pathoadaptive mutations
In collaboration with Dr. Evgeni Sokurenko, we are studying the genome-wide genetic diversity within T. pallidum species and subspecies. These studies use population genomics by analyzing gene presence/absence and single nucleotide polymorphisms across genomes of different strains. The primary goal of is to identify adaptive mutations that facilitate bacterial survival in specific habitats and, in particular, sequence changes associated with different clinical outcomes in humans and the animal model.
- Antigenic Variation
We are studying the tpr gene family of T. pallidum. The Tpr antigens are major targets of the protective immune response and promising vaccine candidates. Our group has identified the first mechanism of antigenic variation in syphilis responsible for the generation of tprK diversity. It involves donor cassettes, one expression site and non-reciprocal gene conversion mechanisms. Experimental data demonstrate sequential acquisition of sequence diversity consistent with this mechanism. In collaboration with Dr. Sheila A. Lukehart, we are comparatively studying the patterns of sequence changes among syphilis isolates during infection, the role of immune pressure in selection of organisms with TprK variants and the implications of TprK diversity in immune evasion.
- TprC and TprD antigens
The TprC and TprD antigens of Treponema pallidum are targets of the humoral and cellular immune responses of the host during syphilis infection. These antigens are predicted to be outer membrane proteins, and they elicit opsonic antibodies upon immunization. TprC and TprD are heterogeneous among T. pallidum subspecies and 3D models show typical ß-barrel structures with surface exposed loops. In collaboration with Dr. Sheila Lukehart, we are studying antigenic differences in surface exposed loops and their significance in functional immunity. Furthermore, in collaboration with Dr. Ram Samudrala, we are actively exploring the identification of continuous and discontinuous epitopes in 3D models in conserved and variable surface-exposed loops and their potential role in cross protective immunity.
Centurion-Lara A, Castro C, Barrett LK, Cameron C, Mostowfi M, Van Voorhis WC, Lukehart SA. Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response. J Exp Med. 1999; 189: 647-56.
• JEM Abstract
Centurion-Lara A, LaFond RE, Hevner K, Godornes C, Molini BJ, Van Voorhis WC, Lukehart SA. Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection. Mol Microbiol. 2004; 52(6): 1579-96.
Giacani L, Lukehart SA, Centurion-Lara A. Length of guanosine homopolymeric repeats modulates promoter activity of Subfamily II tpr genes of Treponema pallidum ssp. pallidum. FEMS Immunol Med Microbiol. 2007; 51(2): 289-301.
Giacani L, Godornes C, Puray-Chavez M, Guerra-Giraldez C, Tompa M, Lukehart SA, Centurion-Lara A. TP0262 is a modulator of promoter activity of tpr Subfamily II genes of Treponema pallidum ssp. pallidum. Mol Microbiol. 2009; 72(5): 1087-99.