Microbiology and Molecular Genetics Michigan State University
2215 Biomedical Physical Sciences East Lansing, MI 48824-4320
Undergrad and Grad Info:
M.P.H. (1998) Hospital and Molecular Epidemiology, University of Michigan, Ann Arbor, Mich.
Ph.D. (2001) Epidemiologic Science, University of Michigan, Ann Arbor, Mich.
Emerging Infectious Disease Fellowship CDC/APHL 2001-2004
University of Michigan, 2001-2002
Michigan State University, 2004-2010
190 Food Safety & Toxicology Building
Michigan State University
East Lansing, MI 48824
My laboratory studies the molecular epidemiology and evolutionary genetics of infectious diseases, namely those caused by diarrheagenic Escherichia coli and Streptococcus agalactiae. More specifically, we apply molecular biology, population genetic, and evolutionary methods to answer questions about pathogenesis, emergence, virulence, evolution, and transmission of pathogens in human and animal populations. Our preliminary studies of both Shiga toxin-producing E. coli (STEC) O157:H7 and S. agalactiae are similar in that the phylogenetic analysis of genotyping data and the subsequent epidemiological analysis identified specific clonal complexes to be more important for disease. Several research projects are associated with these key findings that aim to enhance our understanding of how genetic variation impacts clinical illness. Additional projects involve: i) examining how infection with different enteric pathogens alters the type of microbes, or microbial communities, present in the human intestine; and ii) identifying genetic and environmental factors associated with STEC shedding in cattle.
We also manage and curate the STEC Center: A Reference Center to Facilitate The Study of Shiga Toxin-Producing Escherichia coli.
Also my lab is part of the NIH Center – ERIN: Enteric Disease Research Investigation Network
Overview of STEC studies
Our prior work in the Microbial Evolution Laboratory directed by the late Thomas Whittam has allowed us to better differentiate between STEC O157:H7 strains and identify a subset of strains that more frequently cause severe disease. Through collaborations with Dr. David Alland of the University of Medicine and Dentistry of New Jersey and Bala Swaminathan of the Centers for Disease Control and Prevention, we developed a subtyping method based on SNPs that provides greater resolution of closely related genotypes. An examination of SNP variation at 96 loci in 83 polymorphic O157 genes was applied to 538 human-derived O157:H7 strains from outbreaks, clusters, and sporadic cases worldwide. Pairwise comparisons identified 39 SNP genotypes (SGs) that differ on average at ~20% of SNP loci and were organized into 9 lineages, or clades.
Notably, the subsequent epidemiological analysis identified differences between clades in the frequency and distribution of Shiga toxin (Stx) genes and in the type of clinical disease reported. Hemolytic uremic syndrome (HUS) cases in Michigan were significantly more likely to be infected with strains belonging to clade 8, a lineage that increased in frequency of recovery between 2001 and 2006. Genome sequencing of the 2006 spinach outbreak strain, a member of clade 8 that contributed to remarkably high rates of hospitalization (51%) and HUS (15%) (44), has substantial genomic differences relative to other sequenced O157 genomes (in clades 1 and 3). Some differences were related to stx genotype, as the outbreak strain contained both stx2c and stx2, though significant SNP differences also were identified in conserved backbone genes, or open reading frames of housekeeping genes. Additionally, we observed that clade 8 versus clade 2 strains had an enhanced ability to adhere to bovine mammary epithelial cells, and also had higher expression levels of important O157 virulence genes via transcriptome analysis. Similar findings were obtained when comparing the spinach outbreak strain (clade 8) with the Sakai outbreak strain (clade 1). While it is possible that an emergent subpopulation of clade 8 has acquired critical factors that contribute to more severe disease, the basis for its emergence is not known.
Relevant publicationsAl Safadi, R., G.S. Abu-Ali, R.E. Sloup, J.T. Rudrik, C.M. Waters, K.A Eaton, and S.D. Manning. 2012. Correlation between in vivo biofilm formation and virulence gene expression in Escherichia coli O104:H4. PLoS One. 2012;7(7): e41628.
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