Floyd C. Knoop, Ph.D.

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Appointment(s) and Titles:

Professor, Medical Microbiology and Immunology, Creighton University School of Medicine
Component I Director, Creighton University School of Medicine

Education:

B.S., Biology and Psychology, Defiance College, 1966
M.S., Microbiology, University of Dayton, 1969
Ph.D., Medical Microbiology and Biochemistry, University of
Tennessee Medical Center, 1974
Postdoctoral Fellow, Vibrio cholerae, University of Tennessee Medical Center, 1975

Research Interests:

Diarrhea induced by microbial enterotoxins, and concomitant sequelae of electrolyte imbalance, fluid depletion, malnutrition, and secondary infection, is a central cause of morbidity and mortality worldwide. Like hormones, enterotoxins bind and activate specific receptors on the mammalian cell surface, leading to a cascade of events that profoundly alter mammalian cell physiology. Two distinct microbial enterotoxins, heat-labile and heat-stable, have been recognized. The heat-labile enterotoxin produced by Vibrio cholerae and Escherichia coli has a specific cell receptor, GM₁ ganglioside, and activates the adenylate cyclase system by catalyzing the NAD-dependent ADP-ribosylation of G_sa , the stimulatory guanine nucleotide binding protein, culminating in the elevation of intracellular cyclic AMP and catastrophic diarrheal response. Interests in this laboratory have centered on the heat-stable (ST_a) enterotoxin of E. coli. The purified ST_a enterotoxin was found to be a low molecular weight peptide (~2000) with a specific high-affinity receptor on the mammalian cell surface. Receptor activation signals the stimulation of particulate guanylate cyclase and elevation of intracellular cyclic GMP. In past studies, the ST_a-mediated response in suckling mice and/or cultured rat basophilic leukemia cells was inhibited by indomethacin, a cyclooxygenase antagonist, and by zomepirac sodium and quinacrine hydrochloride, which inhibit the production of prostaglandins. Several pharmacologic agents, including calmodulin antagonists (chlorpromazine and trifluoperazine), calcium channel blockers (diltiazem, nifedipine, and cromolyn sodium) and calcium antagonists (lodoxamide tromethamine and lanthanum) were demonstrated to inhibit the action of ST_a enterotoxin or the cyclic GMP analog 8-bromo cyclic GMP. In other studies the fluorescent cytosolic calcium indicator indo-1 was used to demonstrate an elevation of intracellular calcium during ST_a enterotoxin activation. In addition, a role for particulate protein kinase was found during ST_a activation, suggesting that this enzyme is required for receptor-mediated transmembrane signaling. Based on these and other recent findings a model for cellular activation by ST_a enterotoxin is shown in Figure 1. It should be recognized that each step of the pathway plays an integral part in the cascade of events that ultimately lead to the induction of a cellular response. Other research interests include the role of microbial products, including Clostridium difficile cytotoxin B, in the initiation of disease processes and the role of Chlamydia pneumoniae in cardiovascular diseases.

Selected Publications:

Knoop FC. Experimental infection of rabbit ligated ileal loops with Treponema hyodysenteriae. Infect. Immun. 1979; 26:1196-1201.

Madsen GL, Knoop FC. Physiochemical properties of a heat-stable enterotoxin produced by Escherichia coli of human origin. Infect. Immun. 1980; 28:1051-1053.

Knoop FC. Investigation of a hemolysin produced by enteropathogenic Treponema hyodysenteriae. Infect. Immun. 1981; 31:193-198.

Knoop FC, Abbey DM. Effect of chemical and pharmacological agents on the secretory activity induced by Escherichia coli heat-stable enterotoxin. Can. J. Microbiol. 1981; 27:754-758.

Knoop FC. Effect of heat-stable enterotoxin of Escherichia coli on cultured mammalian cells. J. Infect. Dis. 1983; 147:450-459.

Knoop FC, Thomas DD. Effect of lodoxamide on the secretory response induced by Escherichia coli and Vibrio cholerae enterotoxins in infant mice. Infect. Immun. 1984; 44:406-408.

Clark RB, Knoop FC, Padgitt PJ, Hu DH, Wong JD, Janda JM. Attachment of mesophilic aeromonads to cultured mammalian cells. Curr. Microbiol. 1989; 19:97-102.

Knoop FC, Dworzack DL, Martig RJ, Sterpetti A, Bailey RT, Schultz RD. Bonding of ofloxacin to polytetrafluoroethylene suture and colonization by Staphylococcus aureus. Curr. Microbiol. 1990. 20:27-30.

Knoop FC, Martig RJ, Boehm WJ. Effect of Escherichia coli heat-stable enterotoxin on protein kinase activity in rat enterocytes. Toxicon. 1990; 28:493-500.

Knoop FC, Owens M, Marcus JN, Murphy B. Elevation of calcium in rat enterocytes by Escherichia coli heat-stable (ST_a) enterotoxin. Curr. Microbiol. 1991; 23:291-296.

Knoop FC, Owens M. Pharmacologic action of Escherichia coli heat-stable (ST_a) enterotoxin. J. Pharmacol. Toxicol. Meth. 1992; 28:67-72.

Knoop FC, Owens M, Crocker IC. Clostridium difficile: Clinical disease and diagnosis. Clin. Microbiol. Rev. 1993; 6: 251-265.

Pai J, Knoop FC, Hunter WJ III, Agrawal DK. Chlamydia pneumoniae and occlusive vascular disease: identification and characterization. J. Pharmacol. Physiol. Meth. 1998; 39:51-61.

Goraya, J. F. C. Knoop, and J. M. Conlon, 1998. Ranaturins: antimicrobial peptides isolated from the skin of the American bullfrog, Rana catesbeina. Biochem. Biophys Res. Commun. 250: 589-592.

Wang, Y. F. C. Knoop, I. Remy-Jouet, C. Delarue H. Vaudry, and J. M. Conlon. 1998. Antimicrobial peptides of the brevinin-2 family isolated from gastric tissue of the frog, Rana esculenta. Biochem. Biophys. Res. Commun. 253: 600-603.

Goraya, J. F. C. Knoop and J. M. Conlon, 1999. Ramatierom OT: an antimicrobial peptide isolated from the skin of the frog, Rana temporaria. Peptides. 20: 159-163.

Knoop, F.C. 1999. Adherence of a spirochete to mammalian cell surfaces. Education Instructional Library, International Collection of Microbial Resources for Teaching and Learning, American Society for Microbiology, ASM Digital Image Collection: http://www.asmusa.org/edusrc/library/fknoop/HTMLpages/adherence.htm. Peer reviewed submission,ASM .

Conlon, J. M., T. Halverson, J. Ddddulka, J. E. Platz and F. C. Knoop. 1999. Peptides with antimicrobial activity of the brevinin-1 family isolated from skin secretions of the southern leopard frog, Rana sphenocephala, J. Pept.Res.54(6): 522-527.

Conlon, J. M., T. Halverson, J. Dulka, J. E. Platz, and F. C. Knoop. 2000.
Peptides with antimicrobial activity of the brevinin-1 family isolated
from skin secretions of the southern leopard frog, Rana sphenocephala. J.
Peptide Res. 54:522-527.

Basir, Y. J., F. C. Knoop, J. Dulka, and J. M. Conlon. 2000. Multiple
antimicrobial peptides and peptides related to bradykinin and neuromedin N
isolated from skin secretions of the pickerel frog, Rana palustris.
Biochim Biophys Acta 1543: 95-105

*Goraya, J., Y. Wang, Z. Li, M. O'Flaherty, F. C. Knoop, J. E. Platz, and
J. M. Conlon,. Peptides with antimicrobial activity from four different
families isolated from the skins of the North American frogs, Rana
luteiventris, Rana berlandieri and Rana pipiens. Eur. J. Biochem.
267:894-900, 2000.

*Kim, J.B., T. Halverson, Y. J. Basir, J. Dulka, F. C. Knoop, and J. M.
Conlon. Purification and characterization of antimicrobial peptides from
skin extracts and skin secretions of the North American pig frog Rana
grylio. Regul. Peptides 90:53-60, 2000.

Halverson, T., Y. J. Basir, F. C. Knoop, and J. M. Conlon. Purification
and characterization of antimicrobial peptides from the skin of the North
American green frog Rana clamitans. Peptides 21;469-476, 2000.

*Mattute, B., F. C. Knoop, and J. M. Conlon. Kassinatuerin-I: A peptide
with broad-spectrum antimicrobial activity isolated from the skin of the
Hyperoliid frog, Kassina senegalensis. Biochem. Biophys. Res. Commun.
268:433-436 , 2000.

*Mattute, B., K. B. Storey, F. C. Knoop, and J. M. Conlon. Induction of
synthesis of an antimicrobial peptide in the skin of the freeze-tolerant
frog, Rana sylvatica, in response to environmental stimuli. FEBS Lett.
24209:1-4, 2000.

Kim, J. B., S. Iwamuro, F. C. Knoop, and J. M. Conlon. 2001. Antimicrobial peptides from the skin of the Japanese mountain brown frog, Rana ornativentris. J. Pept. Res. 58(5):349-356.

Ali, M. F., A. Soto, F. C. Knoop, and J. M. Conlon. 2001. Antimicrobial peptides isolated from skin secretions of the diploid frog, Xenopus tropicalis (Pipidae). Biochim. Biophys. Acta. 1550(1): 81-89.

Olson, L. III, A. M. Soto, F. C. Knoop, and J. M. Conlon. 2001. Pseudin-2: an antimicrobial peptide with low hemolytic activity from the skin of the paradoxical frog. Biochim. Biophys. Res. Commun. 288(4):1001-1005.

Isaacson, T., A. M. Soto, S. Iwamuro, F. C. Knoop, and J. M. Conlon. 2002. Antimicrobial peptides with atypical structural features from the skin of the Japanese brown frog Rana japonica. Peptides. 23(3):419-425.

Conlon, J. M., J. B. Kim, B. Mattutte and F. C. Knoop. pp. 871-877. 2001. Antimicrobial peptides from frog skin. In: Perspectives in comparative endocrinology: Unity and diversity, Goos, H. J. T., R. K. Rastogi, H. Vaudry and R. Pierantoni (Eds.). Bologna, Monduzzi Editore.

Ohia, S. E., K. Galt, R. L. O’Brien, M. R. Wilson, T. Cochran, M. Duncan, B. Furlong, J. Ibarrola, and F. Knoop. 2002. Establishing the Creighton University Office of Interprofessional Education. Association of Academic Health Centers, Holmes, D. E. (ed.).

Ali, M. F., K. R. Lips, F. C. Knoop, B. Fritzsch, C. Miller, and J. M. Conlon. 2002. Antimicrobial peptides and protease inhibitors in the skin secretions of the crawfish frog, Rana areolata. Biochem Biophys Acta 1601(1): 55-63.

Knoop, F. 2003. Medical Microbiology and Immunology Review, Biotest Publishing Company, Oxnard, CA

Ali, M., F. C. Knoop, H. Vaudry, and J. M. Conlon. Characterization of novel antimicrobial peptides from the skins of frogs of the Rana esculenta complex.. Peptides 24:955-961, 2003

Coico,R., E. Kachur, V. Lima, and S. Lipper. Guidelines for preclerkship bioterrorism curricula. [member, Delphi panel]. Academic Medicine 79 (4):366-75, 2004

Vander Top, E., M. Gentry-Nielsen, and F. C. Knoop. (2004). Rabies, S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
Available: [http://www.xpharm.com/citation?Article_ID=1476]

Vander Top, E., M. Gentry-Nielsen, and F. C. Knoop. (2004). Trichomoniasis. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
Available: [http://www.xpharm.com/citation?Article_ID=1482]

Vander Top, E., M. Gentry-Nielsen, and F. C. Knoop. (2004). Poliomyelitis. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
Available: [http://www.xpharm.com/citation?Article_ID=1475]

Knoop, F. C. (2004). Typhus Fever. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
Available: [http://www.xpharm.com/citation?Article_ID=1447].

Knoop, F. C. (2004). Diseases Caused by Spirochetes. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1440]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Q Fever. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1451]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Rickettsialpox. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1446]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Borrelia. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1442]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Brill-Zinsser Disease. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1450]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Disease Caused by Treponema pallidum, Non-venereal Trepanematoses and Leptospira. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1441]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Murine (Endemic) Typhus. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1448]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Fusospirochetal Infections. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1443] . Xpharm (web based) : , 2004

Knoop, F. C. (2004). Rickettsial Diseases. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1444]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Rocky Mountain Spotted Fever. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1445]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Scrub Typhus. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1449]. Xpharm (web based) : , 2004

Knoop, F. C. (2004). Trench Fever. S. J. Enna and D. B. Bylund (eds.), xPharm, Elsevier, Inc., New York.
[http://www.xpharm.com/citation?Article_ID=1452]. Xpharm (web based) : , 2004

Knoop, F. 2004. Medical Microbiology and Immunology Review, 2nd ed., Biotest Publishing Company, Ventura, CA

Sonnevend, A., Knoop, F.C., Patel, M., Pál, T., Soto, A.M. and Conlon, J.M. 2004. Antimicrobial properties of the frog skin peptide, ranatuerin-1 and its [Lys- 8]-substituted analog. Peptides 25: 29-36

Honors & Achievements

Postdoctoral Fellow, University of Tennessee Medical Center, 1974-75
Nomination, John F. Kennedy Teaching Award, Student Board of Governors, 1979
Nomination, Mary Lucretia Creighton Award, 1983
Who's Who in Medicine and Healthcare, 1st Edition, 1996

Memberships and Professional Services:

American Society for Microbiology (ASM)
Missouri Valley Branch ASM
American Association for the Advancement of Science (AAAS)
New York Academy of Sciences (NYAS)
Sigma Xi
American Society for Biochemistry and Molecular Biology (ASBMB)
International Center for Diarrheal Diseases (ICDD)
Member, College of American Pathologists (CAP) 1991- 1995
International Society on Toxinology (IST)
Medical Staff, St. Joseph Hospital/Creighton University Medical
Center (SJH)
Nomination, Academy of Clinical Laboratory Physicians and
Scientists, 1993-1997 (ACLPS)

Links:

Creighton University Medical Center
Education Policy Analysis Archives
American Society for Microbiology
Medical World Search
Doctor's Guide
The "Virtual" Medical Center
National Library of Medicine
MedWeb Databases
Cyberoundsv Cholera Enterotoxin/Lunar Lander
Pasteur Institute
Journals on the Web
Online Musicians List

Department of Medical Microbiology and Immunology
2500 California Plaza • Omaha, Nebraska 68178 • (402) 280-2921