Anti-Infectives Screening Core
The Anti-Infectives Screening Core will test candidates, such as drugs, antibodies or peptides, against infectious diseases in vitro and in vivo. This Core facilitates the process of early anti-infectives development by offering in vivo screening in murine models of infection, taking advantage of the specialized facilities and expertise available in the Department of Microbiology at NYU School of Medicine.
The Core tests activity of potential anti-infectives for four neglected diseases: Malaria, Chagas (South American Trypanosomiasis), Human African Trypanosomiasis and Leishmaniasis and one bacterial disease (Staphylococcus aureus infection). However, incorporation of other infectious diseases that have murine models of infection would be contemplated in the future depending on the interests of internal and external users. Potential anti-infectives for testing are provided by users and shipped to the core for testing.
Testing of anti-infective candidates in vivo takes advantage of a new method of parasite detection in mice that allows rapid automated determination without the need for bleeding the animals and manual counting of parasitemias or bacteremias. The method is based on the infection of mice with transgenic parasites or bacteria that express luciferase. Mice are infected with any of the parasites of study: Trypanosoma cruzi for Chagas disease, Trypanosoma brucei ssp. for Human African Trypanosomiasis, Leishmania ssp. for Leishmaniasis and Plasmodium berghei for malaria and Staphylococcus aureus. Two-seven days after infection when there is a detectable blood parasitemia (Trypanosoma and Plasmodia), lesion (Leishmania), bacteremia or organ infection (bacteria), mice are anesthetized and imaged with an imaging device that is sensitive to luminescence (IVIS Lumina, located in OPH 401) and quantifies the signal. Treatment with the test anti-infective candidates begin and is normally administered with i.p. injection for 5 or 10 days at a dose of 10 mg/kg/day. One day after the last treatment dose, mice are imaged again to determine the level of infection. The results are expressed as the ratio of infection at the end of treatment versus the base infection before treatment for each animal. Groups of five mice are used including a negative control group. A positive control with a well-known drug for each disease was performed during the set up of the method (see figure) and it is not included in every experiment. Variations on the standard protocol (days of treatment, dose, route of administration) can be performed in specific cases if demanded by the clients, but will need to be discussed with the core staff.