Faculty and Research

Biography

The overall goal of our research is to understand the mechanisms bacteria use to resist antimicrobials and the host immune system to ultimately guide future therapeutic advances. Bacterial resistance to antibiotics is growing rapidly while few new therapeutics are being introduced to the clinic. This is a major threat to human health as we are reliant on effective antibiotics for many of the modern medical advances which have increased our lifespan. Multi-drug resistant Klebsiella pneumoniae is categorized as “Priority 1: Critical” on the World Health Organization priority pathogens list for R&D of new antibiotics. In addition to being resistant to antibiotics, hypervirulent K. pneumoniae has a robust extracellular polysaccharide capsule that allows it to evade clearance by the host immune system and the spread within the community of healthy individuals.

The major focus of the Fleeman lab is understanding the factors important for robust biofilm formation by K. pneumoniae and how interactions of antimicrobial peptides with extracellular polysaccharides can contribute to biofilm disruption. Specifically, we are investigating: 1) How antimicrobial peptides disrupt robust biofilms by K. pneumoniae, 2) the role that polysaccharides play in biofilm formation by K. pneumoniae, and 3) the role of novel virulence factors in K. pneumoniae pathogenesis. For more information about the research in the Fleeman lab visit our lab webpage:

Link to Lab Webpage

Recent Publications

  1. Robert L. Beckman IV, Berta Martinez, Flor Z. Santiago, Gabriela N. Echeverria, Bruno V. Pinheiro, Marcelo D.T. Torres, Logan Suits, Shantal Garcia, Paeton L. Wantuch, Cesar de la Fuente-Nunez, Prahathees Eswara, David A. Rosen, Renee M. Fleeman. Molecular response to the non-lytic peptide bac7 (1-35) triggers disruption of Klebsiella pneumoniae BioRixv August 11, 2025. DOI: 10.1101/2025.08.08.669280. In Revision at Plos Pathogens.

  2. Robert L. Beckman IV, Elenora Cella, Taj Azarian, Olaya Rendueles, and Renee M. Fleeman. Diverse polysaccharide production and biofilm formation abilities of clinical Klebsiella pneumoniae. npj biofilms and microbiomes. December 19, 2024. DOI: 1038/s41522-024-00629-y.

  3. Laura De los Santos, Robert L. Beckman IV, Christina DeBarro, James E. Keener, Marcelo D. T. Torres, Cesar de la Fuente-Nunez, Jennifer S. Brodbelt, and Renee M. Fleeman. Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilm Cell Reports Physical Science. March 13, 2024. DOI: 10.1016/j.xcrp.2024.101869. Top 4 most read articles of the past 30 days on 4-17-24.

  4. Renee Fleeman. Repurposing Inhibitors of Phosphoinositide 3-kinase as Adjuvant Therapeutics for Bacterial Infections. Frontiers in Antibiotics. Special topic review invite. Feb 9, 2023. DOI:10.3389/frabi.2023.1135485

  5. Renee Fleeman, Michelle Mikesh, and Bryan Davies. Optimization of Klebsiella pneumoniae Biofilm Preparation for Scanning Electron Microscopy Analysis. Feb 3, 2023. DOI:10.1099/acmi.0.000470.v3.

  6. Renee Fleeman, Bryan Davies. Polyproline Peptide Aggregation with Klebsiella pneumoniae Extracellular Polysaccharides Exposes Biofilm Associated Bacteria. Microbiology spectrum. April 27, 2022. DOI 10.1128/spectrum.02027-21.

  7. Justin R. Randall, Gillian Davidson, Renee M. Fleeman, Santos A. Acosta, Ian M. Riddington, Timothy J. Cole, Cory D. DuPai, and Bryan W. Davies. Synthetic discovery and development of symbah-1, a macrocyclic beta-hairpin peptide antibiotic. iScience. January 21, 2022. DOI:10.1016/j.isci.2021.103611.

  8. Renee Fleeman, Luis Macias, Jennifer Brodbelt, and Bryan Davies. Defining principles that influence antimicrobial peptide activity against capsulated Klebsiella pneumoniae. PNAS October 21, 2020. DOI:10.1073/pnas.2007036117.

  9. Danielle H. Demers, Matthew A. Knestrick, Renee Fleeman, Rahmy Tawfik, Ala Azhari, Ashley Souza, Brian Vesely, Mandy Netherton, Rashmi Gupta, Beatrice L. Colon, Christopher A. Rice, Mario A. Rodriguez-Perez, Kyle H. Rohde, Dennis E. Kyle, Lindsey N. Shaw, and Bill J. Baker. Exploitation of Mangrove Endophytic Fungi for Infectious Disease Drug Discovery. Marine Drugs. October 10, 2018. DOI:10.3390/md16100376.

  10. Renee Fleeman, Travis M. LaVoi, Radleigh G. Santos, Angela Morales, Adel Nefzi, Gregory S.Welmaker, José L. Medina-Franco, Marc A. Giulianotti, Richard A. Houghten, and Lindsey N. Shaw. The Development of Novel Anti-Resistance Agents Targeting the Efflux Pumps of Multi-Drug Resistant Bacterial Pathogens. Frontiers in Microbiology. June 14, 2018. DOI:10.3389/fmicb.2018.01301.

  11. Renee Fleeman, Kurt S. Van Horn, Megan M. Barber, Whittney N. Burda, Roman Manetsch, and Lindsey N. Shaw. Characterizing the Antimicrobial Activity of N2,N4-Disubstituted Quinazoline-2,4-Diamines Towards Multidrug Resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. March 13, 2017. DOI:10.1021/jm501628s.

  12. Christine Kirkpatrick, Christopher Broberg, Elijah McCool, Woo Jean Lee, Alex Chao, Evan McConnell, David Pritchard, Michael Hebert, Renee Fleeman, Jessie Adams, Amer Jamil, Laurence Madera, Adam Strömstedt, Ulf Goransson, Yufeng Liu, David Hoskin, Lindsey Shaw, Leslie Hicks. The ‘PRISMS’ pipeline for natural product bioactive peptide discovery. Analytical Chemistry. January 17, 2017. DOI:10.1021/acs.analchem.6b03625.

  13. Andy Wiess, Renee M. Fleeman, Lindsey N. Shaw. Exposing the Unique Connection between Metabolism and Virulence in Staphylococcus aureus. Cell Chemical Biology. November 17, 2016. DOI:10.1016/j.chembiol.2016.11.003.

  14. Yangmei Li, Nina Bionda, Renee Fleeman, Hongjie Wang, Akihiko Ozawa, Richard A. Houghten, Lindsey Shaw. Identification of 5,6-dihydroimidazo[2,1-b] thiazoles as a New Class of Antimicrobial Agents. Bioorganic and medicinal chemistry. November 1, 2016. DOI:10.1016/j.bmc.2016.09.027.

  15. Jacqueline L. von Salm, Christopher G. Witowski, Renee M. Fleeman, James B. McClintock, Charles D. Amsler, Lindsey N. Shaw, and Bill J. Baker. Darwinolide, a New Diterpene Scaffold That Inhibits Methicillin-Resistant Staphylococcus aureus Biofilm from the Antarctic Sponge Dendrilla membranosa. Organic Letters. June 3, 2016. Featured as ACS Editor’s Choice June 30th 2016; 90,000+ views in 2016; most viewed article from ACS. DOI:10.1021/acs.orglett.6b00979.

  16. Nina Bionda, Renee M. Fleeman, César de la Fuente-Núñez, Maria C. Rodriguez, Fany Reffuveille, Lindsey N. Shaw, Irena Pastar, Stephen C. Davis, Robert E. W. Hancock, and Predrag Cudic. Identification of novel cyclic lipopeptides from a positional scanning combinatorial library with enhanced antibacterial and antibiofilm activities. Eur J Med Chem. January 27, 2016. DOI:10.1016/j.ejmech.2015.11.032.

  17. Renee Fleeman, Travis M. LaVoi, Radleigh G. Santos, Angela Morales, Adel Nefzi, Gregory S. Welmaker, José L. Medina-Franco, Marc A. Giulianotti, Richard A. Houghten, and Lindsey N. Shaw. Combinatorial Libraries as a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens. J. Med. Chem. April 23, 2015. DOI:10.1021/jm501628s.

  18. Van Horn K, Burda W, Fleeman RM, Manetsch R, Shaw L. Antibacterial Activity of a Series of N2,N4-Disubstituted Quinazoline-2,4-Diamines. JMedChem. April 10, 2014. DOI:10.1021/jm500039e.

  19. Bionda N, Fleeman RM, Shaw LN, Cudic P. Effect of Ester to Amide or N-methyl Amide Substitution on Membrane Depolarization and Antibacterial Activity of Novel Cyclic Lipopeptides. ChemMedChem. August 8, 2013. DOI: 10.1002/cmdc.201300173.

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