
Alison Criss, PhD
Alison Criss, PhD, the Harrison Distinguished Teaching Professor and vice chair of the Department of Microbiology, Immunology, and Cancer Biology, and colleagues were awarded a five-year, $2.7 million renewal of the NIH-NIAID R01 grant titled “Survival of Neisseria gonorrhoeae after primary human neutrophil challenge.”
The Criss lab investigates the pathogenesis and immune response to Neisseria gonorrhoeae, a bacterium that causes the sexually transmitted infection gonorrhea. Rates of gonorrhea in the United States and worldwide are at sustained highs, with 80-100 million cases estimated globally each year. Complicating treatment of gonorrhea is rampant antibiotic resistance, including the emergence of “superbug” strains that are resistant to all recommended therapies. Without effective therapy, gonorrhea has serious and life-threatening consequences for human health including infertility, chronic pelvic pain, ectopic pregnancy, and inflammation of the heart and joints.
The Criss lab’s research is particularly focused on understanding the role of neutrophils in N. gonorrhoeae pathogenesis. As the most abundant white blood cell in the body, neutrophils have key antimicrobial properties, but they also can cause tissue damage. In gonorrhea, neutrophils do not clear N. gonorrhoeae, and their sustained recruitment to sites of infection is a driver of the inflammatory damage that is characteristic of the disease.
This NIH award will support years 11-15 of ongoing research in the Criss lab to understand the mechanisms used by N. gonorrhoeae to defend itself from neutrophil attack. In this renewal period, they will dissect the mechanisms used by N. gonorrhoeae to bind immunosuppressive factors derived from the human host, which dampen primary human neutrophil activation and bacterial phagocytosis. They will also apply single-cell sequencing and cytometric analysis to investigate how variation of proteins and lipids on the bacterial surface modulates interactions with human neutrophils, including why some neutrophils fail to engulf and kill N. gonorrhoeae in the infection milieu. These studies will be enabled by UVA’s Flow Cytometry Core Facility and Genome Analysis and Technology Core. Findings from this research have implications for host- and bacterial-targeted therapeutics to combat drug-resistant gonorrhea.
Other collaborators on this award include Tania Thomas, MD, UVA Division of Infectious Diseases and International Health; Sanjay Ram, MBBS, and Jutamas Shaugnessy, MD, PhD, Department of Medicine, University of Massachusetts Chan Medical School; Gary Jarvis, PhD, and Constance John, PhD, University of California, San Francisco; and Hervé Tettelin, PhD, University of Maryland School of Medicine.
Filed Under: Research