Arturo Centurion, MD
- Research Associate Professor Emeritus
- University of Washington
- Research Professor
- Universidad Peruana Cayetano Heredia, Peru
- Designing high-resolution genotyping markers for Leptospira spp.
Leptospirosis is a worldwide public health problem of high significance, fatality rates sometimes being as high as one quarter of the affected population. This zoonotic disease is caused by a range of Leptospira species that can be sub-divided into more than 200 serovars. One of the geographical regions that demonstrates high diversity of Leptospira spp. is Amazon basin. In this proposal, we plan to explore the distribution of predominant Leptospira species and clonal groups across Peru. We will sequence genomes from a diverse collection of 400 strains of Leptospira spp. circulating across Peru. We hypothesize that Leptospira, within and across species, is comprised of sequence types (STs) and ST lineages (ST complexes) with a distinct geographical distribution and/or infection phases. Comparative genomic analysis will be performed to distinguish the predominant pathogenic serovars in Peru and to characterize their population diversity and clonal structure. We will map within- and between-species pan-genomic profiles and detect positively selected genes to decipher the genome-wide events of gene presence/absence and gene mutations. This will be followed by genome-wide association studies and data mining to test our hypothesis that certain Leptospira genes are linked to specific clinical manifestations or geographical sources via their presence/absence or accumulated positively-selected mutations. All the analysis-results will be available publicly to set the stage for future studies, expanding our understanding on the development of effective control strategies for leptospirosis.
- Congenital syphilis
Research interest is directed at understanding patterns of antibody responses in pregnant women and newborns during syphilis infection. Specifically, we are interested in antibody responses to T. pallidum antigens in pregnant women as predictors of effective treatment, and immunoproteome profiles in mothers and newborns associated with particular clinical outcomes
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.
• PubMed Abstract
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.
• PubMed Abstract
Centurion-Lara A, Giacani L, Godornes C, Molini BJ, Brinck Reid T, Lukehart SA. Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains. PLoS Negl Trop Dis. 2013 16;7(5):e2222.
• PubMed Abstract