Discipline: Biological Sciences
Sarah Hsieh - Johns Hopkins University
Co-Author(s): Travis Nielsen, Jun Yan, Brad Spellberg , Department of Medicine and Department of Molecular Microbiology & Immunology, Keck School of Medicine at the University of Southern California (USC), Los Angeles, CA
Acinetobacter baumannii is a gram-negative, multi-drug resistant species of bacteria that is becoming increasingly problematic and difficult to treat in the hospital setting. Our lab has developed an antibody, MAb C8, that targets this deadly species and effectively lowers the bacterial burden of infected mice. The purpose of this experiment is to determine how the antibody works and with which innate immune effectors does it interact with to show the greatest clearance of bacteria in the blood. Mice were depleted of either their neutrophils, complement, or macrophages and infected with HUMC1, a strain of Acinetobacter baumannii. Blood was collected at 2 hours post-infection via tail vein knick, and the blood was diluted and plated for CFU counting. Groups treated with the antibody showed significantly lower bacterial burden compared to the placebo groups. It seems that complement shows the most efficacious interaction with MAb C8 antibody, as seen in the larger difference in CFUs/mL of blood between the placebo group and MAb C8 treated group. It was found that the MAb C8 antibody treatment effectively clears bacteria from the blood in all groups. MAb C8 treatment improves survival rates for all groups. Complement interaction with MAb C8 shows the greatest clearance of bacteria, followed by neutrophils, then macrophages. The triple depleted mice cleared more bacteria in the when treated with antibody compared to placebo mice. This could be due to immune complex formation, where the anitbody binds to the bacteria but does not phagocytose them. Several CFUs will appear as only one colony, resulting in a lower CFU count. Future research will include repeating the experiment to confirm results as well as looking into the possible effects of cytokines and the inflammation they cause that worsens infections. References: Nielsen T., Pantapalangkoor P., Luna B., Bruhn K., Yan J., Dekitani K., Hsieh S., “Monoclonal Antibody Protects against Acinetobacter baumannii infection by Enhancing Bacterial Clearance and Evading Sepsis”, The Journal of Infectious Diseases. Accepted for Publication on 6/27/17 PMID: TBD, DOI: TBDNot Submitted
Funder Acknowledgement(s): This study was supported by grants R01 AI1081719, R21 AI101750, R41 AI106375, R42 AI106375, and R56 AI104751 awarded to Dr. Brad Spellberg, MD?FIDSA FACP, Chief Medical Officer, LAC+USC Medical Center, Associate Dean for Clinical Affairs, Professor of Clinical Medicine, Division of Infectious Diseases Keck School of Medicine at USC, Los Angeles, CA
Faculty Advisor: Travis Nielsen, firstname.lastname@example.org
Role: This experiment was done mostly on my own with the assistance of my mentor and another lab assistant because of the large number of mice that were needed for blood collection and CFU plating. I was part of the planning, executing, and data analyzing and collecting aspects of the research, guided by my mentor.