Dr. Daniel C. Nelson

Daniel C. Nelson, Associate Professor

Head of the Laboratory of Antimicrobial Discovery

Education

2003: M.B.A.  Zicklin School of Business, Baruch College, City University of New York

1999-2004: Postdoctoral training in Bacterial Pathogenesis and Immunology. Rockefeller University, New York, NY

1999: Ph.D. in Biochemistry and Molecular Biology. University of Georgia, Athens

1993: B.S. in Biology.  University of California, Irvine

Professional Experience

2014 - Present: Associate Professor, Institute for Bioscience & Biotechnology Research (IBBR) Rockville, MD and the Department of Veterinary Medicine, College Park, Maryland

2012 - Present: Affiliate Professor, Department of Cell Biotenology and Molecular Genetics, University of Maryland, College Park, Maryland

2010 - Present: Guest Researcher, National Institute for Standards and Technology (NIST), Gaithersburg, Maryland

2010 - 2014: Assitant Professor, Institute for Bioscience And Technology Research (IBBR), Rockville, Maryland and the Department of Veterinary Medicine, College Park, Maryland

2009 - Present: Subject Matter Expert, Infectious Diseases, Department of Defense

2009 - Present: Member, Biological Sciences Graduate Program, Concentration area: Molecular & Cellular Biology, University of Maryland, College Park,  Maryland

2007 - 2010: Adjunction Faculty, Rocketller University, NY

2007 - 2010: Assistant Professor, Center for Advanced Research in Biotechnology (CARB), University of Maryland Biotechnology Institute (UMBI), Rockville , Maryland

2005 - 2007: Research Assistant Professor, Bacterial Pathogenesis and Immunology, Rockefeller University, NY

1999 - 2004: Posdoctoral Fellow in the lab of Vincent A. Fischetti, Rockefeller University, NY

1993 - 1999: Graduate Fellow, University of Georgia, Athens

Research Interests

The alarming increase of multidrug‐resistant bacteria, the emergence of new pathogens, and the desire to reduce/eliminate antimicrobial use in agriculture products have prompted new antimicrobial discovery initiatives. Researchers seek to identify and develop alternative antimicrobial therapeutics that are not susceptible to traditional antibiotic resistance mechanisms.

The Nelson laboratory is at the forefront of antimicrobial discovery and develops a class of bacteriophage-derived peptidoglycan hydrolase enzymes, called endolysins, and applies them to bacterial pathogens. These enzymes act on contact to rapidly degrade the bacterial cell wall of both animal and human pathogens, resulting in osmotic lysis of the membrane and death of the bacterial cell.

The Nelson lab works with endolysins effective against methicillin‐resistant Staphylococcus aureus (i.e. MRSA), Clostridium difficile, Streptococcus pyogenes, and Bacillus anthracis (anthrax) that cause human disease. On the animal side, they have endolysins effective against Streptococcus equi (equine strangles disease), Streptococcus suis (meningitis and other infections in pigs), Streptococcus uberis (bovine mastitis), and Staphylococcus aureus (bovine mastitis).

Dr. Nelson brings together the unique ability to cross disciplines and effectively incorporate cell biology, microbiology, and structural biology with bioengineering approaches to advance endolysin research and discovery. Employing rational methods (computational design or chimeragenesis) and random methods (directed evolution), his group is generating endolysins with more desirable attributes, such as higher activity, an expanded host range, a more favorable thermostability profile, or the ability to enter human cells to kill intracellular pathogens. It is anticipated that these bioengineering approaches will result in development of the next-generation endolysins with enhanced properties.

Representative Publications

Shang X, Nelson DC. Contributions of net charge on the PlyC endolysin CHAP domain.Antibiotics (Basel). 2019 May 28;8(2). pii: E70. doi: 10.3390/antibiotics8020070.
PMID: 31142020

Greenfield J, Shang X, Luo H, Zhou Y, Heselpoth RD, Nelson DC, Herzberg O. Structure and tailspike glycosidase machinery of ORF212 from E. coli O157:H7 phage CBA120 (TSP3). Sci Rep. 2019 May 14;9(1):7349. doi: 10.1038/s41598-019-43748-9. PMID: 31089181

Schuch R, Pelzek AJ, Nelson DC, Fischetti VA. The PlyB endolysin of bacteriophage vB_BanS_Bcp1 exhibits broad-spectrum bactericidal activity against Bacillus cereus sensu lato isolates. Appl Environ Microbiol. 2019 Apr 18;85(9). pii: e00003-19. doi: 10.1128/AEM.00003-19. PMID: 30850428

Harhala M, Nelson DC, Miernikiewicz P, Heselpoth RD, Brzezicka B, Majewska J, Linden SB, Shang X, Szymczak A, Lecion D, Marek-Bukowiec K, Kłak M, Wojciechowicz B, Lahutta K, Konieczny A, Dąbrowska K. Safety studies of pneumococcal endolysins Cpl-1 and Pal. Viruses. 2018 Nov 15;10(11). pii: E638. doi: 10.3390/v10110638. PMID: 30445722

Etobayeva I, Linden SB, Alem F, Harb L, Rizkalla L, Mosier PD, Johnson AA, Temple L, Hakami RM, Nelson DC. Discovery and biochemical characterization of PlyP56, PlyN74, and PlyTB40-Bacillus specific endolysins. Viruses. 2018 May 21;10(5). pii: E276. doi: 10.3390/v10050276. PMID: 29883383

Zhuang X, Yang X, Altieri AS, Nelson DC, Pal U. Borrelia burgdorferi surface-located Lmp1 protein processed into region-specific polypeptides that are critical for microbial persistence. Cell Microbiol. 2018 Sep;20(9):e12855. doi: 10.1111/cmi.12855. Epub 2018 May 25. PMID: 29749010

Scholte CM, Nelson DC, Garcia M, Linden SB, Elsasser TH, Kahl S, Qu Y, Moyes KM. Recombinant bacteriophage endolysin PlyC is nontoxic and does not alter blood neutrophil oxidative response in lactating dairy cows. J Dairy Sci. 2018 Jul;101(7):6419-6423. doi: 10.3168/jds.2017-13908. Epub 2018 May 3. PMID: 29729914

Yang H, Bi Y, Shang X, Wang M, Linden SB, Li Y, Li Y, Nelson DC, Wei H. Antibiofilm activities of a novel chimeolysin against Streptococcus mutans under physiological and cariogenic conditions. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7436-7443. Print 2016 Dec. PMID: 27736755

Becker SC, Roach DR, Chauhan VS, Shen Y, Foster-Frey J, Powell AM, Bauchan G, Lease RA, Mohammadi H, Harty WJ, Simmons C, Schmelcher M, Camp M, Dong S, Baker JR, Sheen TR, Doran KS, Pritchard DG, Almeida RA, Nelson DC, Marriott I, Lee JC, Donovan DM. Triple-acting lytic enzyme treatment of drug-resistant and intracellular Staphylococcus aureus. Sci Rep. 2016 Apr 28;6:25063. doi: 10.1038/srep25063. PMID: 27121552

Shen Y, Barros M, Vennemann T, Gallagher DT, Yin Y, Linden SB, Heselpoth RD, Spencer DJ, Donovan DM, Moult J, Fischetti VA, Heinrich F, Lösche M, Nelson DC.  A bacteriophage endolysin that eliminates intracellular streptococci. Elife. 2016 Mar 15;5. pii: e13152. doi: 10.7554/eLife.13152. PMID: 26978792