Christopher S. Hayes

Biography

Dr. Hayes received his B.A. (Biology) and M.S. (Applied Immunology) degrees from the University of Southern Maine, and his Ph.D. in Molecular Biology & Biochemistry from the University of Connecticut School of Medicine. He was a Walter Winchell-Damon Runyon Cancer Research Fund postdoctoral fellow at the Massachusetts Institute of Technology and joined the MCDB faculty in 2004.

Research

All bacteria compete for growth niches and other limited resources in both the environment and within eukaryotic hosts. These existential battles are waged at several levels, but one common strategy entails the transfer of growth-inhibitory protein toxins directly between competing bacterial cells. Toxic antibacterial effectors are invariably encoded together with immunity proteins, which specifically neutralize toxin activity to prevent auto-inhibition. Antibacterial effector-immunity protein pairs are extraordinarily diverse in sequence, and each immunity protein only provides protection against its cognate toxin. Thus, toxin-immunity protein polymorphism underpins an important mechanism of self/nonself discrimination in bacteria. The Hayes lab is interested in the structure, function and physiology of specialized secretion systems that mediate inter-bacterial conflict. Because these toxin-delivery systems readily penetrate bacterial cell envelopes, they are of considerable interest for the development of novel approaches to antimicrobial therapy.

Selected Publications

Costello, M. S., Neumann, B., Raimondi, M. W., Cuthbert, B. J., Holubová, J., Garza-Sánchez, F., Samad, A., Bumba, L., Torres, J. A., Holznecht, N. Mendoza, J., Stanek, O., Prombhul, S., Weimbs, T., Morrissey, M. A., Acosta-Alvear, D., Low, D. A., Šebo, P., Goulding, C. W., Gonen, S. and C. S. Hayes (2026) Bacteria deliver a microtubule-binding protein into mammalian cells to promote colonization. Science 391:825-830

Jensen, S. J., Cuthbert, B. J., Garza-Sánchez, F., Helou, C. C., de Miranda, R., Goulding, C. W. and C. S. Hayes (2024) Advanced glycation end-product (AGE) crosslinking activates a type VI secretion system phospholipase effector protein. Nature Communications 15:8804

Bartelli, N. L., Passanisi, V. J., Michalska, K., Song, K., Nhan, D. Q., Zhou, H., Cuthbert, B. J., Stols, L. M., Eschenfeldt, W. H., Wilson, N. G., Basra, J. S., Cortes, R., Noorsher, Z., Gabraiel, Y., Poonen-Honig, I., Seacord, E. C., Goulding, C. W., Low, D. A., Joachimiak, A., Dahlquist, F. W. and C. S. Hayes (2022) Proteolytic processing induces a conformational switch required for antibacterial toxin delivery. Nature Communications 13:5078

Halvorsen, T. M, Garza-Sánchez, F., Ruhe, Z. C., Bartelli, N. L., Chan, N. A., Nguyen, J. Y., Low, D. A. and C. S. Hayes (2021) Lipidation of class IV CdiA effector proteins promotes target-cell recognition during contact- dependent growth inhibition (CDI). mBio 12:e0253021

Donato, S. L., Beck, C. M., Garza-Sánchez, F., Jensen, S. J., Ruhe, Z. C., Cunningham, D. A., Singleton, I., Low, D. A. and C. S. Hayes (2020) The β-encapsulation cage of rearrangement hotspot (Rhs) effectors is required for type VI secretion. Proceedings of the National Academy of Sciences U.S. A. 117:33540-33548

Ruhe, Z. C., Subramanian, P., Song, K., Nguyen, J. Y., Stevens, T. A., Low, D. A., Jenson, G. J., and C. S. Hayes (2018) Programmed secretion arrest and receptor-triggered toxin export during antibacterial contact-dependent growth inhibition. Cell 175:921-933

Michalska, K., Gucinski, G. C., Garza-Sánchez, F., Johnson, P. M., Stols, L., Eschenfeldt, W. H., Babnigg, G., Low, D. A., Goulding, C. W., Joachimiak, A., and C. S. Hayes (2017) Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific tRNAs. Nucleic Acids Research 45:10306-10320

Ruhe, Z. C., Nguyen, J. Y., Xiong, J., Koskiniemi, S, Beck, C. M., Perkins, B. R., Low, D. A. and C. S. Hayes (2017) Toxic CdiA effectors recognize target bacteria using modular receptor-binding domains. mBio 8:e00290-17

Beck, C. M., Willett, J. L. E., Cunningham, D. A., Kim, J. J., Low, D. A. and C. S. Hayes (2016) CdiA effectors from uropathogenic Escherichia coli use heterotrimeric osmoporins as receptors to recognize target bacteria. PLOS Pathogens 12:e1005925

Willett, J. L. E., Gucinski, G. C., Fatherree, J., Low, D. A., and C. S. Hayes (2015) Contact-dependent growth inhibition (CDI) toxins exploit multiple independent cell-entry pathways. Proceedings of the National Academy of Sciences U.S.A. 112:11341-11346

Ruhe, Z. C., Nguyen, J. Y., Beck, C. M., Low, D. A. and C. S. Hayes (2014) The proton-motive force is required for translocation of CDI toxins across the inner membrane of target bacteria. Molecular Microbiology 94:466-481

Beck, C. M., Morse, R. P., Cunningham, D. A., Iniquez, I., Low, D. A., Goulding, C. W. and C. S. Hayes (2014) CdiA from Enterobacter cloacae delivers a toxic ribosomal RNase into target bacteria. Structure 22:707-718

Koskiniemi, S., Lamoureux, J. G., Nikolakakis, K. C., t’Kint de Roodenbeke, C., Kaplan, M. D., Low, D. A. and C. S. Hayes (2013) Rhs proteins from diverse bacteria mediate intercellular competition. Proceedings of the National Academy of Sciences U.S.A. 110:7032-7037

Diner, E. J., Beck, C. M., Webb, J. S., Low, D. A. and C. S. Hayes (2012) Identification of a target cell permissive factor required for contact-dependent growth inhibition (CDI). Genes and Development 26:515-525

Aoki, S. K., Diner, E. J., t'Kint de Roodenbeke, C., Burgess, B. R., Poole, S. J., Braaten, B. A., Jones, A. M., Webb, J. S., Hayes, C. S., Cotter, P. A. and D. A. Low (2010) A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria. Nature 468:439-442