Professor of Microbiology
Office Location: Health Sciences, J267A
Campus Box: 357735
Dr. Evgeni Sokurenko holds an M.D. and a Ph.D. in medical microbiology from the Moscow Medical Academy, Russian Federation. His postdoctoral research involved structure/functional analysis of the Escherichia coli fimbrial adhesins at the University of Tennessee, Memphis.
Research in Sokurenko's laboratory is focused on understanding mechanisms of molecular adaptive evolution of genes in bacterial pathogens. There are three ongoing projects in the lab:
The first project is directed towards understanding the mechanism of bacterial adhesion to host cells mediated by the most common kind of bacterial adhesins known - type 1, or mannose-sensitive, fimbriae. These studies are devoted to the structure/functional analysis of allelic variations of the E. coli type 1 fimbrial adhesin, FimH protein. Some of these variations result in adaptive changes of the receptor-specificity of type 1 fimbriae that lead to an increased tissue tropism and, consecutively, virulence of uropathogenic and meningitis-associated E. coli. We use purified oligosaccharide compounds of defined structure to map the conformation of the FimH receptor-binding site. We also employ site-directed mutagenesis and Steered Molecular Dynamics simulations (in collaboration with the Center for Nanotechnology, UW, Seattle) to understand the functional effect of structural changes in FimH that are induced by mechanical force under various flow conditions.
The second project is focused on identification of the 'selection footprints' of nucleotide polymorphisms that affect various types of genes encoding different adhesins of E. coli, Shigella and Salmonella strains. These studies employ methods of both evolutionary genetics and molecular biology to discover pathogenicity-adaptive variation of the genes. We believe that our studies will lead to development of an algorithm for the analysis of single nucleotide polymorphisms (SNPs) in the alleles that are responsible for the adaptive differences between commensal and pathogenic isolates of the same species.
Finally, Sokurenko's laboratory is studying how on the genomic level adaptive mutations are accumulated in Pseudomonas aeruginosa and other bacteria during a single infection, e.g. in patients with cystic fibrosis or chronic urinary tract infection. Such adaptive microevolution of microbial clones can be responsible for the persistent and refractory nature of chronic infections. We have developed an effective assay for the detection of minor genetic differences between bacterial clones on a genomic scale. This technique utilizes a DNA mismatch-specific enzyme, CEL I, for screening mutated regions within fractionated genomic restriction fragments. We also employ high-density genomic microarrays to identify adaptive alterations in the gene expression or gene composition of sequential strains isolated from individual patients at different stages of their infections.
Research Resources Developed:
Zonal Phylogeny Software (ZPS): An application that provides distribution about single nucleotide polymorphims (SNPs) of synonymous (silent) and non-synonymous (amino acid) nature along branches of a given DNA tree of protein-encoding gene locus, allowing visualization of recent adaptive evolution through selection of advantageous structural mutations, even when advantage of such mutations is relatively short-lived.
Sokurenko, E.V., V. Chesnokova, D.E. Dykhuzien, I. Ofek, X.-R. Wu, K.A. Krogfelt, C. Struve, M.A. Schembri, and D.L. Hasty. Pathogenic Adaptation of Escherichia coli by Natural Variation of the FimH Adhesin. Proceedings of the National Academy of Sciences of the USA, Vol. 95, pp. 8922-8926. (1998).
Sokurenko, E.V., D.L. Hasty, and D.E. Dykhuzien. Pathoadaptive Mutations: Gene Loss and Variation in Bacterial Pathogens. Trends in Microbiology, Vol. (5), pp. 191-195. (1999).
Sokurenko E.V., M. Schembri, E. Trintchina, K. Kjaergaard, D. Hasty and P. Klemm. (From the Cover), Valency Conversion in the Type 1 Fimbrial Adhesin of Escherichia coli. Molecular Microbiology, 2001, 41(3), pp. 675-686.
Sokurenko E.V., V. Tchesnokova, A. Yeung, C. Oleykowski, E. Trintchina, K. Hughes, R. Rashid, M. Brint, S. Moseley, and S. Lory. Detection of Simple Mutations and Polymorphisms in Large Genomic Regions. Nucleic Acids Research Vol 29, No. 22, p. e111 (2001).
Thomas W.E., E. Trintchina, M. Forero, V. Vogel, and E. V. Sokurenko. Bacterial adhesion to target cells enhanced by shear force. Cell, June 28, 109(7): 913-23 (2002).