Dr. Thomas S. Whittam

My laboratory studies the evolution and emergence of pathogenic bacteria. Through the analysis of molecular polymorphisms, we are investigating the genetic and phenotypic changes underlying the origin and spread of new pathogens. This research has elucidated the ancestry of Escherichia coli O157:H7, a pathogen of zoonotic origin that emerged in the 1980s. Since that time this food and waterborne pathogens has caused hundreds of outbreaks and thousands of sporadic causes of illness. The long-term objective of this work, which involves collaboration with scientists from around the world, is to understand the global distribution of Shiga toxin-producing E. coli (STEC) and other pathogenic varieties of E. coli and the dispersion of specific virulence genes in human populations and animal reservoirs. We are also working on the rapid development of single nucleotide polymorphism (SNP) markers for subtyping O157 strains. We continue to maintain the STEC Reference Center (www.shigatox.net) that supplies strains and information to participating researchers. The STEC Center is based at the National Food Safety and Toxicology Center (NFSTC). The project is supported by National Institute of Allergy and Infectious Diseases of the NIH through Food and Waterborne Diseases Integrated Research Network.

In collaboration with the Michigan Department of Community Health (MDCH), we have been investigating the prevalence of STEC in Michigan through an active surveillance system established by the MDCH. We are analyzing clinical STEC isolates for allelic variation at conserved genes by DNA sequencing. Future work will focus on assessing whether specific genotypes are associated with other bacterial or host characteristics (e.g., age, gender, disease severity).

Genetic Diversity and Molecular Epidemiology of Group B Streptococcus. Group B Streptococcus (GBS) is the primary cause of invasive infections (e.g., bacteremia and meningitis) in newborns and pregnant women and an increasingly important cause of disease in the elderly. In collaboration with Dr. Dele Davies (Pediatrics), we are engaged in a molecular epidemiologic investigation of invasive GBS isolates and maternal colonizing isolates. Our goals are to elucidate the relationships between different virulence genes with GBS colonization and invasion, and to develop a multilocus gene profiling system that would be useful for future epidemiologic and evolutionary studies of this organism. This project is supported by NIH.

Global Phylogeny of Mycobacterium tuberculosis based on Single Nucleotide Polymorphism (SNP) Analysis. Tuberculosis is a globally distributed infectious disease with an estimated 1 billion persons infected with the bacterial agent Mycobacterium tuberculosis. In collaboration with Dr. David Alland and other researchers at the Center for the Study of Emerging and Reemerging Pathogens at UMDNJ, we are analyzing a worldwide collection of M. tuberculosis isolates using SNP markers. The SNP markers have been used to test hypothesis about the history and geographic spread of tuberculosis.

Acid resistance among Shiga toxin-producing Escherchia coli in food matrices. Pathogenic strains of E. coli, such as E. coli O157:H7, have been shown to be unusually acid resistant, surviving acidic conditions typically expected to inactivate bacteria. Adaptations for survival in low pH environments may also contribute to risk of foodborne illness. These adaptations could account for the low infectious dose (10 to 100 cells) and ability to contaminate acidic foods, such as apple cider. The study aims to measure acid resistance of bacteria representing major clonal groups of pathogenic E. coli and to assess the effect of incubation in food matrices on subsequent survival in a simulated gastric environment. This project is supported by USDA.