Alison K. Criss

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Primary Appointment

Professor, Microbiology, Immunology, and Cancer Biology

Education

  • BA, Biology and Chemistry, Williams College
  • PhD, Cell and Developmental Biology, Harvard University
  • Postdoc, Microbiology, Northwestern University

Research Disciplines

Cell and Developmental Biology, Immunology, Infectious Diseases/Biodefense

Research Interests

Cellular and molecular mechanisms of Neisserial pathogenesis

Research Description

Our laboratory studies N. gonorrhoeae, an obligate human bacterial pathogen that causes the sexually transmitted infection gonorrhea. Gonorrhea has existed within the human population for all of recorded history and remains the second-most commonly reported bacterial sexually transmitted infection in the world today. Gonorrhea continues to be a major public health problem because of rapid acquisition of antibiotic resistance (the CDC identified N. gonorrhoeae as a highest priority superbug threat in 2013), the lack of protective vaccines, the fact that previously infected individuals remain susceptible to re-infection, and the predisposition of infected individuals to acquisition of HIV.
Since N. gonorrhoeae has no niche outside of humans, the biology of this organism is exquisitely tailored to life in the human urogenital tract. Not only is N. gonorrhoeae able to exploit the nutritional and environmental conditions at this site, but the bacterium also has an extraordinary ability to thwart challenges by the host immune response. N. gonorrhoeae evades humoral immune recognition by undergoing extensive variation of its surface structures, including high-frequency sequence changes in the N. gonorrhoeae pilin gene that lead to antigenic variation of the type IV pilus. N. gonorrhoeae is also highly adept at surviving confrontations with the innate immune system. Acute gonorrhea is a highly inflammatory disease characterized by the production of an exudate containing large numbers of neutrophils. Although neutrophils are the body's first defenders against bacterial and fungal challenge, neutrophils are ineffective at killing N. gonorrhoeae, and gonorrheal exudates contain viable, infectious bacteria.
Our research is currently centered on identifying how N. gonorrhoeae resists neutrophil clearance. We are addressing how neutrophils recognize N. gonorrhoeae, which antimicrobial activities neutrophils direct against N. gonorrhoeae, and how N. gonorrhoeae withstands or thwarts these activities. We use a combination of cell biology, molecular biology, bacterial genetics and biochemistry to address these questions. The insights gleaned from these studies will help us to understand in general how the mucosal innate immune system defends against infection and how pathogens exploit mucosal defenses to aid in colonization and transmission.

Ngonorrhoeae-infected-neutrophil-criss.jpg

Thin-section transmission electron micrograph of N. gonorrhoeae-infected neutrophil.

humanneutrophilsinfectedwNgonorrhoeae.jpg

Fluorescence/phase-contrast image of human neutrophils infected with strain FA1090 N. gonorrhoeae for 60 minutes. Green particles are intracellular bacteria; red/yellow particles are extracellular bacteria.

Personal Statement

Our laboratory studies Neisseria gonorrhoeae, an obligate human bacterial pathogen that causes the sexually transmitted infection gonorrhea. Gonorrhea has existed within the human population for all of recorded history and remains the second-most commonly reported bacterial sexually transmitted infection in the world today. Gonorrhea continues to be a major public health problem because of rapid acquisition of antibiotic resistance (the CDC identified N. gonorrhoeae as an "urgent," highest level superbug threat in 2013), the failure of vaccines to stimulate a protective immune response, the fact that previously infected individuals remain susceptible to subsequent rounds of re-infection, and the predisposition of infected individuals to acquisition of HIV.
Since N. gonorrhoeae has no niche outside of humans, the biology of this organism is exquisitely tailored to life in the human urogenital tract. Not only is N. gonorrhoeae able to exploit the nutritional and environmental conditions at this site, but the bacterium also has an extraordinary ability to thwart challenges by the host immune response. N. gonorrhoeae evades humoral immune recognition by undergoing extensive variation of its surface structures, including high-frequency sequence changes in the N. gonorrhoeae pilin gene that lead to antigenic variation of the type IV pilus. N. gonorrhoeae is also highly adept at surviving confrontations with the innate immune system. Acute gonorrhea is a highly inflammatory disease characterized by the production of an exudate containing large numbers of neutrophils. Although neutrophils are the body's first defenders against bacterial and fungal challenge, neutrophils are ineffective at killing N. gonorrhoeae, and gonorrheal exudates contain viable, infectious bacteria.
Our research is currently centered on identifying how N. gonorrhoeae resists clearance by the human innate immune system. We are addressing how neutrophils recognize N. gonorrhoeae, which antimicrobial activities neutrophils direct against N. gonorrhoeae, and how N. gonorrhoeae withstands or thwarts these activities. We use a combination of cell biology, molecular biology, bacterial genetics and biochemistry to address these questions. The insights gleaned from these studies will help us to understand in general how the mucosal innate immune system defends against infection and how pathogens exploit mucosal defenses to aid in colonization and transmission. Specific areas of interest are outlined below.
Resistance of neutrophils to non-oxidative neutrophil killing: We have found that a significant proportion of N. gonorrhoeae presented to primary human neutrophils in vitro survive early infection and grow in association with them over time. Neutrophils generate reactive oxygen species (ROS) such as hydrogen peroxide and hypochlorous acid as part of their antimicrobial arsenal, but inhibition of neutrophil ROS production has no effect on N. gonorrhoeae survival. In the course of these studies, we identified bacterial mutants that are more sensitive to non-oxidative neutrophil killing. We plan to examine which non-oxidative neutrophil factors are active against N. gonorrhoeae and the reasons for the susceptibility of our bacterial mutants to non-oxidative neutrophil killing. We have also gained evidence that neutrophil phagosomes contain viable N. gonorrhoeae. We plan to characterize the neutrophil subcellular compartment(s) in which N. gonorrhoeae are found and examine their maturation over time.
N. gonorrhoeae suppression of neutrophil ROS production: In examining why neutrophil oxidative mechanisms are dispensable for killing of N. gonorrhoeae, we made the surprising observation that neutrophils generate little to no ROS after infection with exponentially-growing N. gonorrhoeae. Moreover, N. gonorrhoeae infection suppresses the ability of neutrophils to generate ROS in response to a variety of stimuli, including S. aureus and formylated peptides. We hypothesize that live N. gonorrhoeae produce factors that interfere with signaling pathways that normally lead to neutrophil ROS production. We are examining how N. gonorrhoeae impede neutrophil signal transduction and which bacterial gene products are responsible for this effect.

30GRID.jpg

Thin-section transmission electron micrograph of N. gonorrhoeae-infected neutrophil. FA1090.jpgN. gonorrhoeae for 60 minutes. Green particles are intracellular bacteria; red/yellow particles are extracellular bacteria.

Training

  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
  • Global Biothreats Training Program
  • Infectious Diseases Training Program
  • Interdisciplinary Training Program in Immunology
  • Training in Cell and Molecular Biology
  • Training in the Pharmacological Sciences

Selected Publications

2022

Alcott, A. M., Werner, L. M., Baiocco, C. M., Dufrisne, M. B., Columbus, L., & Criss, A. K. (2022). Variable Expression of Opa Proteins by Neisseria gonorrhoeae Influences Bacterial Association and Phagocytic Killing by Human Neutrophils. JOURNAL OF BACTERIOLOGY, 204(4). doi:10.1128/jb.00035-22

Ray, J. C., Smirnov, A., Maurakis, S. A., Harrison, S. A., Ke, E., Chazin, W. J., . . . Criss, A. K. (2022). Adherence Enables Neisseria gonorrhoeae to Overcome Zinc Limitation Imposed by Nutritional Immunity Proteins. INFECTION AND IMMUNITY, 90(3). doi:10.1128/iai.00009-22

2021

Criss, A. K., Genco, C. A., Gray-Owen, S. D., Jerse, A. E., & Seifert, H. S. (2021). Challenges and Controversies Concerning Neisseria gonorrhoeae-Neutrophil Interactions in Pathogenesis.. mBio, 12(3), e0072121. doi:10.1128/mbio.00721-21

2020

Werner, L. M., Palmer, A., Smirnov, A., Dufrisne, M. B., Columbus, L., & Criss, A. K. (2020). Imaging Flow Cytometry Analysis of CEACAM Binding to Opa-Expressing Neisseria gonorrhoeae. CYTOMETRY PART A, 97(10), 1081-1089. doi:10.1002/cyto.a.24037

Ragland, S. A., Gray, M. C., Melson, E. M., Kendall, M. M., & Criss, A. K. (2020). Effect of Lipidation on the Localization and Activity of a Lysozyme Inhibitor in Neisseria gonorrhoeae. JOURNAL OF BACTERIOLOGY, 202(8). doi:10.1128/JB.00633-19

Smirnov, A., Solga, M. D., Lannigan, J., & Criss, A. K. (2020). Using Imaging Flow Cytometry to Quantify Neutrophil Phagocytosis. NEUTROPHIL: METHODS AND PROTOCOLS, 3RD EDITION, 2087, 127-140. doi:10.1007/978-1-0716-0154-9_10

2019

Allen, L. -A. H., & Criss, A. K. (2019). Cell intrinsic functions of neutrophils and their manipulation by pathogens. CURRENT OPINION IN IMMUNOLOGY, 60, 124-129. doi:10.1016/j.coi.2019.05.004

Maurakis, S., Keller, K., Maxwell, C. N., Pereira, K., Chazin, W. J., Criss, A. K., & Cornelissen, C. N. (2019). The novel interaction between Neisseria gonorrhoeae TdfJ and human S100A7 allows gonococci to subvert host zinc restriction. PLOS PATHOGENS, 15(8). doi:10.1371/journal.ppat.1007937

Kuhn, J., Smirnov, A., Criss, A. K., & Columbus, L. (2019). Quantifying Carcinoembryonic Antigen-like Cell Adhesion Molecule-Targeted Liposome Delivery Using Imaging Flow Cytometry. MOLECULAR PHARMACEUTICS, 16(6), 2354-2363. doi:10.1021/acs.molpharmaceut.8b01274

Ragland, S. A., & Criss, A. K. (2019). Protocols to Interrogate the Interactions Between Neisseria gonorrhoeae and Primary Human Neutrophils. NEISSERIA GONORRHOEAE: METHODS AND PROTOCOLS, 1997, 319-345. doi:10.1007/978-1-4939-9496-0_19

2018

Palmer, A., & Criss, A. K. (2018). Gonococcal Defenses against Antimicrobial Activities of Neutrophils. TRENDS IN MICROBIOLOGY, 26(12), 1022-1034. doi:10.1016/j.tim.2018.07.003

Handing, J. W., Ragland, S. A., Bharathan, U. V., & Criss, A. K. (2018). The MtrCDE Efflux Pump Contributes to Survival of Neisseria gonorrhoeae From Human Neutrophils and Their Antimicrobial Components. FRONTIERS IN MICROBIOLOGY, 9. doi:10.3389/fmicb.2018.02688

Stevens, J. S., Gray, M. C., Morisseau, C., & Criss, A. K. (2018). Endocervical and Neutrophil Lipoxygenases Coordinate Neutrophil Transepithelial Migration to Neisseria gonorrhoeae. JOURNAL OF INFECTIOUS DISEASES, 218(10), 1663-1674. doi:10.1093/infdis/jiy347

Ragland, S. A., Humbert, M. A. V., Christodoulides, M., & Criss, A. K. (2018). Neisseria gonorrhoeae employs two protein inhibitors to evade killing by human lysozyme. PLOS PATHOGENS, 14(7). doi:10.1371/journal.ppat.1007080

Stevens, J. S., & Criss, A. K. (2018). Pathogenesis of Neisseria gonorrhoeae in the female reproductive tract: neutrophilic host response, sustained infection, and clinical sequelae. CURRENT OPINION IN HEMATOLOGY, 25(1), 13-21. doi:10.1097/MOH.0000000000000394

2017

Criss, A. K., & Tang, C. (2017). Neisseria: recent advances and future challenges. PATHOGENS AND DISEASE, 75(8). doi:10.1093/femspd/ftx090

Ragland, S. A., & Criss, A. K. (2017). From bacterial killing to immune modulation: Recent insights into the functions of lysozyme. PLOS PATHOGENS, 13(9). doi:10.1371/journal.ppat.1006512

Smirnov, A., Solga, M. D., Lannigan, J., & Criss, A. K. (2017). High-Throughput Particle Uptake Analysis by Imaging Flow Cytometry.. Current protocols in cytometry, 80, 11.22.1-11.22.17. doi:10.1002/cpcy.19

Ragland, S. A., Schaub, R. E., Hackett, K. T., Dillard, J. P., & Criss, A. K. (2017). Two lytic transglycosylases in Neisseria gonorrhoeae impart resistance to killing by lysozyme and human neutrophils. CELLULAR MICROBIOLOGY, 19(3). doi:10.1111/cmi.12662

2016

Jean, S., Juneau, R. A., Criss, A. K., & Cornelissen, C. N. (2016). Neisseria gonorrhoeae Evades Calprotectin-Mediated Nutritional Immunity and Survives Neutrophil Extracellular Traps by Production of TdfH. INFECTION AND IMMUNITY, 84(10), 2973-2985. doi:10.1128/IAI.00319-16

Martin, J. N., Ball, L. M., Solomon, T. L., Dewald, A. H., Criss, A. K., & Columbus, L. (2016). Neisserial Opa Protein-CEACAM Interactions: Competition for Receptors as a Means of Bacterial Invasion and Pathogenesis. BIOCHEMISTRY, 55(31), 4286-4294. doi:10.1021/acs.biochem.6b00124

2015

Smirnov, A., Solga, M. D., Lannigan, J., & Criss, A. K. (2015). An improved method for differentiating cell-bound from internalized particles by imaging flow cytometry. JOURNAL OF IMMUNOLOGICAL METHODS, 423, 60-69. doi:10.1016/j.jim.2015.04.028

Juneau, R. A., Stevens, J. S., Apicella, M. A., & Criss, A. K. (2015). A Thermonuclease of Neisseria gonorrhoeae Enhances Bacterial Escape From Killing by Neutrophil Extracellular Traps. JOURNAL OF INFECTIOUS DISEASES, 212(2), 316-324. doi:10.1093/infdis/jiv031

Handing, J. W., & Criss, A. K. (2015). The lipooligosaccharide-modifying enzyme LptA enhances gonococcal defence against human neutrophils. CELLULAR MICROBIOLOGY, 17(6), 910-921. doi:10.1111/cmi.12411

Johnson, M. B., Ball, L. M., Daily, K. P., Martin, J. N., Columbus, L., & Criss, A. K. (2015). Opa plus Neisseria gonorrhoeae exhibits reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes. CELLULAR MICROBIOLOGY, 17(5), 648-665. doi:10.1111/cmi.12389

2014

Smirnov, A., Daily, K. P., & Criss, A. K. (2014). Assembly of NADPH Oxidase in Human Neutrophils Is Modulated by the Opacity-Associated Protein Expression State of Neisseria gonorrhoeae. INFECTION AND IMMUNITY, 82(3), 1036-1044. doi:10.1128/IAI.00881-13

2013

Johnson, M. B., & Criss, A. K. (2013). Fluorescence Microscopy Methods for Determining the Viability of Bacteria in Association with Mammalian Cells. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (79). doi:10.3791/50729

Johnson, M. B., & Criss, A. K. (2013). Neisseria gonorrhoeae phagosomes delay fusion with primary granules to enhance bacterial survival inside human neutrophils. CELLULAR MICROBIOLOGY, 15(8), 1323-1340. doi:10.1111/cmi.12117

Ball, L. M., & Criss, A. K. (2013). Constitutively Opa-Expressing and Opa-Deficient Neisseria gonorrhoeae Strains Differentially Stimulate and Survive Exposure to Human Neutrophils. JOURNAL OF BACTERIOLOGY, 195(13), 2982-2990. doi:10.1128/JB.00171-13

Stohl, E. A., Dale, E. M., Criss, A. K., & Seifert, H. S. (2013). Neisseria gonorrhoeae Metalloprotease NGO1686 Is Required for Full Piliation, and Piliation Is Required for Resistance to H2O2- and Neutrophil-Mediated Killing. MBIO, 4(4). doi:10.1128/mBio.00399-13

2012

Criss, A. K., & Seifert, H. S. (2012). A bacterial siren song: intimate interactions between Neisseria and neutrophils. NATURE REVIEWS MICROBIOLOGY, 10(3), 178-190. doi:10.1038/nrmicro2713

2011

Schook, P. O. P., Stohl, E. A., Criss, A. K., & Seifert, S. (2011). The DNA-binding activity of the Neisseria gonorrhoeae LexA orthologue NG1427 is modulated by oxidation. MOLECULAR MICROBIOLOGY, 79(4), 846-860. doi:10.1111/j.1365-2958.2010.07491.x

Johnson, M. B., & Criss, A. K. (2011). Resistance of Neisseria gonorrhoeae to neutrophils. FRONTIERS IN MICROBIOLOGY, 2. doi:10.3389/fmicb.2011.00077

2010

LeCuyer, B. E., Criss, A. K., & Seifert, H. S. (2010). Genetic Characterization of the Nucleotide Excision Repair System of Neisseria gonorrhoeae. JOURNAL OF BACTERIOLOGY, 192(3), 665-673. doi:10.1128/JB.01018-09

Criss, A. K., Bonney, K. M., Chang, R. A., Duffin, P. M., LeCuyer, B. E., & Seifert, H. S. (2010). Mismatch Correction Modulates Mutation Frequency and Pilus Phase and Antigenic Variation in Neisseria gonorrhoeae. JOURNAL OF BACTERIOLOGY, 192(1), 316-325. doi:10.1128/JB.01228-09