Calcutt, Michael
Associate Professor

Dr. Calcutt’s research focuses on aspects of the molecular genetics and pathogenesis of Mycoplasmas, a diverse genus of cell wall-less bacteria that includes many important pathogens of food animals and humans. In the absence of a cell wall, the single limiting membrane represents the unique and critical interface between the pathogen and host.

Understanding the repertoire, function and potential antigenic variation of surface membrane proteins is one of the on-going research interests in the laboratory, with particular emphasis on the Mycoplasma mycoides cluster of ruminant pathogens. In collaboration with Dr. Kim Wise (MMI, MU), the complete genome sequence of one member of this cluster, M. capricolumsubsp. capricolum, is being determined at the Institute for Systems Biology (Seattle, WA). Analysis of the sequence generated to date has already led to the identification of two families of surface proteins, that are predicted to undergo high frequency phase variation (a reversible molecular switch in expression status) that may contribute to host adaptation. The genome sequencing project and surface protein variation studies are supported by the USDA/ARS Program for Prevention of Animal Infectious Diseases (PPAID).

A second research interest is in the function and mobility of several novel genetic elements that have been identified recently. Among these are ICEF and ICEC (integrative, conjugal elements of M. fermentans and M. capricolum, respectively) the first members of a new family of mycoplasma genetic element. These elements contain homologs of plasmid conjugation genes, but are integrated into the chromosomes of certain mycoplasma species. The elements are flanked by direct repeats that are likely generated by target site duplication (which is a hallmark of integrating mobile DNAs). As ICEF and ICEC lack recognizable homologs of integrases or recombinases, it is anticipated that novel proteins are responsible for promoting the integration/excision of these elements. Studies funded by the National Institutes of Health (NIH) are underway to identity the genes encoding such proteins and to characterize the DNA binding sites at which the DNA binding proteins act. ; In addition to the ICE units, additional mobile elements have been identified, including a previously unrecognized bacteriophage genome (in collaboration with Dr. Kim Wise), several IS elements and a novel plasmid replicon. As there is a general paucity of vectors for the genetic manipulation of mycoplasmas, our laboratory is interested in the possible exploitation of these mobile DNAs as tools for the molecular dissection of various aspects of mycoplasma pathobiology.

Ongoing collaborative projects include:
Genome sequencing of animal pathogens (Mark A. McIntosh and Kim S. Wise, MMI)
Characterization of novel gene islands in swine mycoplasmas (Mark A. McIntosh, MMI)
Antigenic variation of surface lipoproteins in M. capricolum (Kim S. Wise, MMI)
Biochemical analysis of bacterial phospatases (Tom J. Reilly, Dept. of Veterinary Pathobiology)
Recombinant enzymes for blood group antigen seroconversion (Daniel Smith, Dept. of Pathology)
Genome Instability in Salmonellae (Abraham Eisenstark, Cancer Research Center)