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Katie Freeman   Dr.  Senior Scientist or Principal Investigator 
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Katie Freeman published an article in April 2019.
Top co-authors See all
Gill Diamond

51 shared publications

Department of Oral Biology, University of Florida, Gainesville, Florida

Hydar Ali

24 shared publications

Department of Pathology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA

Kartikeya Cherabuddi

19 shared publications

University of Florida College of Medicine, Gainesville, Florida

Jeffry C. Pelletier

8 shared publications

Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Road, Doylestown, Pennsylvania 18902, United States

Richard W. Scott

4 shared publications

Fox Chase Chemical Diversity Center, Doylestown, PA 18902, USA

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Article 0 Reads 0 Citations Small-Molecule Host-Defense Peptide Mimetic Antibacterial and Antifungal Agents Activate Human and Mouse Mast Cells via ... Ibrahim Alkanfari, Katie B. Freeman, Saptarshi Roy, Tahsin J... Published: 03 April 2019
Cells, doi: 10.3390/cells8040311
DOI See at publisher website ABS Show/hide abstract
Host-defense peptides (HDPs) have an important therapeutic potential against microbial infections but their metabolic instability and cellular cytotoxicity have limited their utility. To overcome these limitations, we utilized five small-molecule, nonpeptide HDP mimetics (smHDPMs) and tested their effects on cytotoxicity, antimicrobial activity, and mast cell (MC) degranulation. None of the smHDPMs displayed cytotoxicity against mouse 3T3 fibroblasts or human transformed liver HepG2 cells. However, one compound had both antifungal and antibacterial activity. Surprisingly, all five compounds induced degranulation in a human MC line, LAD2, and this response was substantially reduced in Mas-related G protein-coupled receptor (GPCR)-X2 (MRGPRX2)-silenced cells. Furthermore, all five compounds induced degranulation in RBL-2H3 cells expressing MRGPRX2 but this response was abolished in cells expressing naturally occurring loss-of-function missense variants G165E (rs141744602) and D184H (rs372988289). Mrgprb2 is the likely mouse ortholog of human MRGPRX2, which is expressed in connective tissue MCs (CTMCs) such as cutaneous and peritoneal MCs (PMCs). All five smHDPMs induced degranulation in wild-type PMCs but not in cells derived from Mrgprb2-/- mice. These findings suggest that smHDPMs could serve as novel targets for the treatment of drug-resistant fungal and bacterial infections because of their ability to harness CTMCs’ host defense functions.
Article 1 Read 0 Citations Antifungal Potential of Host Defense Peptide Mimetics in a Mouse Model of Disseminated Candidiasis Mobaswar Hossain Chowdhury, Lisa Kathleen Ryan, Kartikeya Ch... Published: 27 February 2018
Journal of Fungi, doi: 10.3390/jof4010030
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC) present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP) exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C. albicans and NAC. Here, we expand upon our previous works to describe the in vitro and in vivo activity of 11 new HDP mimetics that are active against C. albicans and NAC that are both sensitive and resistant to standard antifungal drugs. These compounds exhibit minimum inhibitory/fungicidal concentration (MIC/MFC) in the µg/mL range in the presence of serum and are inhibited by divalent cations. Rapid propidium iodide influx into the yeast cells following in vitro exposure suggested that these HDP mimetics were also membrane active. The lead compounds were able to kill C. albicans in an invasive candidiasis CD-1 mouse model with some mimetic candidates decreasing kidney burden by 3–4 logs after 24 h in a dose-dependent manner. The data encouraged further development of this new anti-fungal drug class for invasive candidiasis.
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