Michael P. Motley
B.S., Biological Sciences, Cornell University 2012, cum laude
7th Year MSTP
3rd Year Medical Student
Bettina Fries, MD.
Medicine, Stony Brook University
Microbiology & Immunology
Title: The role of anti-capsular antibodies in protection against carbapenem-resistant Klebsiella pneumoniae
The gram-negative bacteria Klebsiella pneumoniae ST258 clone (CR-Kp) has become a growing threat in the United States and worldwide. CR-Kp has infected an increasing percentage of patients in healthcare settings and is associated with high mortality due to the ability of CR-Kp to resist multiple classes of antibiotics, including broad-spectrum carbapenems. As a result, there are ongoing efforts to find new classes of drugs to combat this infection, including monoclonal antibodies. One potential target of these antibodies is capsular polysaccharide (CPS), which serves as a means of immune evasion for the bacteria. While CPS often has high variability among the Klebsiella species as a whole, most CR-Kp strains in the United States are highly conserved and belong to the single clonal group ST258, and the CPS of different strains within subgroups this clone show enough congruency to cross-react with the same antibody. The Fries Laboratory has developed murine monoclonal antibodies against ST258 CPS and have characterized their ability to mediate infection by ST258 clinical strains in vitro and in vivo. My project involved investigating anti-capsular vaccine strategies, as well as studying the role that antibody IgG subclass played in promoting protection against ST258 and testing these antibodies across additional models of Kp infection. In doing so, I found additional evidence that anti-capsular antibodies cross-react within capsular subgroups, and found evidence that neutrophils assist in antibody-mediated clearance of CR-Kp at high inoculums.
(MSTP-supported publications indicated with an *)
*Banerjee K, Motley MP, Diago-Navarro E, Fries BC. Serum Antibody Responses Against Carbapenem-Resistant Klebsiella Pneumoniae in Infected Patients. mSphere. 2021; Mar 3;6(2):e01335-20. PubMed: 33658281
*Motley MP, Diago-Navarro E, Banerjee K, Inzerillo S, Fries BC. The Role of IgG Subclass in Antibody- Mediated Protection against Carbapenem-Resistant Klebsiella pneumoniae. mBio. 2020. 11(5):e02059-20. PubMed: 32900809
*Motley MP, Bennett-Guerrero E, Fries BC, Spitzer ED. Review of Viral Testing (Polymerase Chain Reaction) and Antibody/Serology Testing for Severe Acute Respiratory Syndrome-Coronavirus-2 for the Intensivist. Crit Care Explor. 2020;2(6):e0154. PubMed: 32696013; PubMed Central: PMC7314351.
*Motley MP, Banerjee K, Fries BC. Monoclonal antibody-based therapies for bacterial infections. Curr Opin Infect Dis. 2019; 32(3):210-6. PubMed: 30950853; PubMed Central: PMC7050834.
*Diago-Navarro E, Motley MP, Ruiz-Peréz G, Yu W, Austin J, Seco BMS, Xiao G, Chikhalya A, Seeberger PH, Fries BC. Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant Klebsiella pneumoniae Protect from Infection. mBio. 2018; 9(2):e00091-18. PubMed: 29615497;PubMed Central: PMC5885035.
*Motley MP, Fries BC. A New Take on an Old Remedy: Generating antibodies against multidrug-resistant gram-negative bacteria in a post-antibiotic world. mSphere. 2017 Sep-Oct;2(5). PubMed: 28989972; PubMed Central: PMC5628292.
Motley MP ^ , Madsen DH ^ , Jürgensen HJ, Spencer DE, Szabo R, Holmbeck K, Flick MJ, Lawrence DA, Castellino FJ, Weigert R, Bugge TH. A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo. Blood. 2016; 127(9):1085-96. PubMed: 26647393; PubMed Central: PMC4778161. ^ Equal Contribution
Hagarman JA, Motley MP, Kristjansdottir K, Soloway PD. Coordinate regulation of DNA methylation and H3K27me3 in mouse embryonic stem cells. PLoS One. 2013;8(1):e53880. PubMed: 23326524; PubMed Central: PMC3543269.