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 two Gram positive bacteria, the model organism Bacillus subtilis and the opportunistic human pathogen Clostridium difficile, sense and respond to extracellular signals. We are particularly interested in understanding the response of C. difficile to factors produced by the innate immune system. 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.

Our work has revealed the presence of an Extra Cytoplasmic Function (ECF) s factor, sV, present in B. subtilis and C. difficile that is activated specifically by lysozyme, an essential component of the innate immune system. We have found that sV is required for lysozyme resistance in both organisms. We have also found that sV is required for C. difficile to cause disease in an animal model of infection. The activity of sV is inhibited by the anti-sigma factor RsiV. Activation of sV 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 sV activation and understanding the mechanism by which site-1 cleavage of RsiV, and thus sV 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.

A second area of focus for the laboratory is the process of cannibalism which occurs during B. subtilis sporulation. We are interested in understanding both the mechanisms of toxin production and how the senses and responds to the toxin SDP. Sporulation is initiated by the activation of a response regulator, Spo0A. The activity of Spo0A is not uniform across all cells of the population, in fact two subpopulations of B. subtilis exist, Spo0A-ON cells and Spo0A-OFF cells. The Spo0A-ON cells produce a toxin, SdpC, which is secreted and kills the SpoOA-OFF siblings. Normally, the Spo0A-ON cells resist the toxic effects of SDP by producing a membrane protein, SdpI, which provides immunity to the toxin. The immunity protein is only produced when extracellular toxin is present. Interestingly, SdpI is also required to induce its own expression in response to extracellular toxin sequestering a transcriptional repressor, SdpR, to the membrane. The sequestration of SdpR by the SdpC/SdpI complex inhibits the activity of the repressor thereby allowing increased transcription of sdpI, and immunity to the toxin.

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. Journal of Bacteriology. DOI: 10.1128/JB.00663-17.

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.

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 sV Activation. PLoS Genet, 12(9), e1006287. PMID: 27602573.

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.

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.

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.

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.

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., 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., 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. (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.