Craig D. Ellermeier, PhD

Portrait
Associate Professor of Microbiology and Immunology

Contact Information

Office: 201 Eckstein Medical Research Building
431 Newton Rd
Iowa City, IA 52242
319-384-4565

Lab: 200H Eckstein Medical Research Building
431 Newton Rd
Iowa City, IA 52242
319-335-7622

Education

BS, Microbiology, Iowa State University
MS, Microbiology, University of Illinois at Urbana-Champaign
PhD, Microbiology, University of Illinois at Urbana-Champaign

Postdoctoral Fellow, Harvard University

Education/Training Program Affiliations

Biomedical Science Program, Department of Microbiology Graduate Program, Interdisciplinary Graduate Program in Genetics, Medical Scientist Training Program

Research Summary

Work in the Ellermeier Lab focuses on how Gram-positive bacteria sense and respond to extracellular signals. Our work is focused on the opportunistic human pathogen Clostridium difficile and the model organism Bacillus subtilis. We are interested in understanding how cells respond to changes in their environment by altering gene expression. To alter gene expression bacteria must detect changes in their environment and then transduce that signal from outside the cell to a transcriptional response inside the cell. We are interested in understanding the basic molecular mechanisms involved in how cells sense and respond to extracellular signals. We utilize genetic, molecular, biochemical and structural approaches to dissect these signal transduction systems.

We are particularly interested in understanding the response of C. difficile to factors produced by the innate immune system. Our work has revealed the presence of an Extra Cytoplasmic Function (ECF) σ factor, σV, present in C. difficile and B. subtilis as well as other Gram-positive bacteria that is activated specifically by lysozyme, an essential component of the innate immune system. We have found that σV is required for lysozyme resistance in both B. subtilis and C. difficile. The activity of σV is inhibited by the anti-sigma factor RsiV. Activation of σV occurs via proteolytic destruction of an anti-sigma factor RsiV. This degradation occurs only in the presence of lysozyme and requires multiple proteases to destroy RsiV in a process of regulated intramembrane proteolysis (RIP). We are interested in identifying the proteases required for σV activation and understanding the mechanism by which site-1 cleavage of RsiV, and thus σV activation, is controlled. We are also studying the role of additional ECF sigma factors encoded by C. difficile to determine their role in response to cell envelope stress. In addition, we are interested in understanding the role of these ECF sigma factors play in survival of the bacterium during an infection.

Publications

Castro, A. N., Lewerke, L. T., Hastie, J. L. & Ellermeier, C. D. (2018). Signal Peptidase Is Necessary and Sufficient for Site 1 Cleavage of RsiV in Bacillus subtilis in Response to Lysozyme. J Bacteriol, 200(11), e00663-17. PMID: 29358498.

Hastie, J. L., Ellermeier, C. D. (2016). Proteolytic activation of extra cytoplasmic function (ECF) s factors. In F. J. De Brujin (Eds.) Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria. pp. 344. Wiley.

Ransom, E. M., Weiss, D. S. & Ellermeier, C. D. (2016). Use of mCherryOpt Fluorescent Protein in Clostridium difficile. In Methods Mol Biol. pp. 53-67. Springer. PMID: 27507333.

Hastie, J. L., Williams, K. B., Bohr, L. L., Houtman, J. C., Gakhar, L. & Ellermeier, C. D. (2016). The Anti-sigma Factor RsiV Is a Bacterial Receptor for Lysozyme: Co-crystal Structure Determination and Demonstration That Binding of Lysozyme to RsiV Is Required for s<sup>V</sup> Activation. PLoS Genet, 12(9), e1006287. PMID: 27602573.

Ho, T. D., Ellermeier, C. D. (2015). Ferric Uptake Regulator Fur Control of Putative Iron Acquisition Systems in Clostridium difficile. J Bacteriol, 197(18), 2930-40. PMID: 26148711.

Ransom, E. M., Ellermeier, C. D. & Weiss, D. S. (2015). Use of mCherry Red fluorescent protein for studies of protein localization and gene expression in Clostridium difficile. Appl Environ Microbiol, 81(5), 1652-60. PMID: 25527559.

Ransom, E. M., Williams, K. B., Weiss, D. S. & Ellermeier, C. D. (2014). Identification and characterization of a gene cluster required for proper rod shape, cell division, and pathogenesis in Clostridium difficile. J Bacteriol, 196(12), 2290-2300. PMID: 24727226.

Ho, T. D., Williams, K. B., Chen, Y., Helm, R. F., Popham, D. L. & Ellermeier, C. D. (2014). Clostridium difficile extracytoplasmic function s factor sV regulates lysozyme resistance and is necessary for pathogenesis in the hamster model of infection. Infect Immun, 82(6), 2345-55. PMID: 24664503.

Hastie, J. L., Williams, K. B., SepĂșlveda, C., Houtman, J. C., Forest, K. T. & Ellermeier, C. D. (2014). Evidence of a bacterial receptor for lysozyme: binding of lysozyme to the anti-s factor RsiV controls activation of the ecf s factor sV. PLoS Genet, 10(10), e1004643. PMID: 25275625.

PĂ©rez Morales, T., Ho, T. D., Liu, W. T., Dorrestein, P. C. & Ellermeier, C. D. (2013). Production of the cannibalism toxin SDP is a multistep process that requires SdpA and SdpB. J Bacteriol, 195(14), 3244-51. PMID: 23687264.

Hastie, J. L., Williams, K. B. & Ellermeier, C. D. (2013). The activity of sV, an extracytoplasmic function s factor of Bacillus subtilis, is controlled by regulated proteolysis of the anti-s factor RsiV. J Bacteriol, 195(14), 3135-44. PMID: 23687273.

Ho, T. D., Ellermeier, C. D. (2012). Extra cytoplasmic function s factor activation. Curr Opin Microbiol, 15(2), 182-8. PMID: 22381678.

Ho, T. D., Hastie, J. L., Intile, P. J. & Ellermeier, C. D. (2011). The Bacillus subtilis extracytoplasmic function s factor s(V) is induced by lysozyme and provides resistance to lysozyme. J Bacteriol, 193(22), 6215-22. PMID: 21856855.

Ho, T. D., Ellermeier, C. D. (2011). PrsW is required for colonization, resistance to antimicrobial peptides, and expression of extracytoplasmic function s factors in Clostridium difficile. Infect Immun, 79(8), 3229-38. PMID: 21628514.

Liu, W. T., Yang, Y. L., Xu, Y., Lamsa, A., Haste, N. M., Yang, J. Y., Ng, J., Gonzalez, D., Ellermeier, C. D., Straight, P. D., Pevzner, P. A., Pogliano, J., Nizet, V., Pogliano, K. & Dorrestein, P. C. (2010). Imaging mass spectrometry of intraspecies metabolic exchange revealed the cannibalistic factors of Bacillus subtilis. Proc Natl Acad Sci U S A, 107(37), 16286-90. PMID: 20805502.

Smith, J. N., Dyszel, J. L., Soares, J. A., Ellermeier, C. D., Altier, C., Lawhon, S. D., Adams, L. G., Konjufca, V., Curtiss, R., Slauch, J. M. & Ahmer, B. M. (2008). SdiA, an N-acylhomoserine lactone receptor, becomes active during the transit of Salmonella enterica through the gastrointestinal tract of turtles. PLoS One, 3(7), e2826. PMID: 18665275.

Ellermeier, C. D., Losick, R. (2006). Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis. Genes Dev, 20(14), 1911-22. PMID: 16816000.

Ellermeier, C. D., Hobbs, E. C., Gonzalez-Pastor, J. E. & Losick, R. (2006). A three-protein signaling pathway governing immunity to a bacterial cannibalism toxin. Cell, 124(3), 549-59. PMID: 16469701.

Ellermeier, C. D., Ellermeier, J. R. & Slauch, J. M. (2005). HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium. Mol Microbiol, 57(3), 691-705. PMID: 16045614.

Merighi, M., Ellermeier, C. D., Slauch, J. M. & Gunn, J. S. (2005). Resolvase-in vivo expression technology analysis of the Salmonella enterica serovar Typhimurium PhoP and PmrA regulons in BALB/c mice. J Bacteriol, 187(21), 7407-16. PMID: 16237024.

Ellermeier, C. D., Slauch, J. M. (2005). The Genus Salmonella. In M. Dworkin (Eds.) The Prokaryotes: An Evolving Electronic Resource for the Microbiological Community. (3rd edition) Springer-Verlag, New York.

Ellermeier, C. D., Slauch, J. M. (2004). RtsA coordinately regulates DsbA and the Salmonella pathogenicity island 1 type III secretion system. J Bacteriol, 186(1), 68-79. PMID: 14679226.

Ellermeier, C. D., Slauch, J. M. (2003). RtsA and RtsB coordinately regulate expression of the invasion and flagellar genes in Salmonella enterica serovar Typhimurium. J Bacteriol, 185(17), 5096-108. PMID: 12923082.

Ellermeier, C. D., Janakiraman, A. & Slauch, J. M. (2002). Construction of targeted single copy lac fusions using lambda Red and FLP-mediated site-specific recombination in bacteria. Gene, 290(1-2), 153-61. PMID: 12062810.

Stanley, T. L., Ellermeier, C. D. & Slauch, J. M. (2000). Tissue-specific gene expression identifies a gene in the lysogenic phage Gifsy-1 that affects Salmonella enterica serovar typhimurium survival in Peyer's patches. J Bacteriol, 182(16), 4406-13. PMID: 10913072.