Alison D. O'Brien, Ph.D.

Alison D. O'Brien, Ph.D.

alison obrien

Name: Alison D. O'Brien, Ph.D.

Department of Primary Appointment: Microbiology & Immunology
Position: Department Chair
Title: Professor & Chair, Ph.D.

Affiliated Departments: Molecular & Cell Biology, Emerging Infectious Diseases

Email: alison.obrien@usuhs.edu (link sends e-mail)
Office Phone: (301) 295-3419

Links
Department Website

Education

University
Ohio State University School of Medicine

Profile

Research: Molecular Mechanisms of Bacterial Pathogenesis

The objective of the major program in the laboratory is to define the molecular mechanisms by which enterohemorrhagic Escherichia coli (EHEC) cause hemorrhagic colitis and the hemolytic uremic syndrome. EHEC are food-borne pathogens that cause outbreaks of disease associated with ingestion of undercooked hamburgers or raw milk.  Such an outbreak occurred in 1993 in the Pacific Northwest. EHEC are characterized by the production of Shiga toxins (Stxs) and the capacity to adhere avidly to the large bowel epithelium.  Our studies on the virulence mechanisms of EHEC include: creation of molecular tools (monoclonal antibodies and DNA probes) for detecting toxin, investigation of the molecular genetics and regulation of toxin synthesis, purification and characterization of toxins, development of small animal models to further clarify pathogenic traits of EHEC, and analysis of the molecular mechanisms by which EHEC adhere to epithelial cells.

HEp-2 cells infected with EHEC O157:H7On the left is a fluorescent image of HEp-2 cells infected with EHEC O157:H7. Polymerized actin (red), Tir (blue), and nucleolin (green) appear to be closely associated with the adherent bacteria. On the right is a phase contrast image of the same cell. (courtesy of Dr. James Sinclair).

Another project in my laboratory investigates the virulence factors of and host response to enteroaggregative E. coli strains that were isolated from deployed military personnel with travelers' diarrhea.  This is a collaborative research effort with Dr. David Tribble and CAPT Mark Riddle in PMB and IDCRP and Dr. Stephen Davies in MIC.

My laboratory also studies the roles of toxins and capsules in the pathogenesis of the highly pathogenic Bacillus cereus G9241 strain. B. cereus G9241 caused anthrax-like lung disease and produces the anthrax toxins.  It also makes two distinct polysaccharide capsules and a unique ADP-ribosyltransferase called Certhrax.

 

Selected Publications:

 

1.        Scheutz, F., L.D. Teel, L. Beutin, D. Piérard, G. Buvens, H. Karch, A. Melmann, A. Caprioli, R. Tozzoli, A.R. Melton-Celsa, M. Sanchez, S. Persson, N.A. Strockbine and A.D. O’Brien.  2012. Multi-center evaluation of a sequence-based protocol for subtyping Shiga toxins and standardizing Stx nomenclature. J. Clin. Microbiol.  50:2951-2963.  PMID: 22760050.

2.        Cote, C.K., L. Kaatz, J. Reinhardt, J. Bozue, S.A. Tobery, A.D. Bassett, P. Sanz, S.C. Darnell, F. Alem, A.D. O’Brien, and S.L. Welkos.  2012.  Characterization of a multi-component anthrax vaccine designed to target the initial stages of infection as well as toxemia.  J. Med. Microbiol.  61:1380-1392.  PMID: 22767539.

3.        Mallick, E.M., M.E. McBee, V.K. Vanguri, A.R. Melton-Celsa, K. Schlieper, B.J. Karalius, A.D. O’Brien, J. Butterton, J. Leong, and D. Schauer.  2012.  A novel murine model for Shiga toxin-producing Escherichia coli infection.  J. Clin. Invest. 122: 4012-4024.  PMID: 23041631.

4.        Garcia, T.A., C.L. Ventura, M.A. Smith, D.S. Merrell, and A.D. O’Brien.  2013.  Cytotoxic necrotizing factor 1 and hemolysin from uropathogenic Escherichia coli elicit different host responses in the murine bladder.  Infect. Immun. 81:99-109.  PMID: 23090961.

5.        Vergis, J.M., Cote, C.K., Bozue, J., Alem F., Ventura, C.L., Welkos, S.L., O’Brien A.D. 2013. Immunization of mice with formalin-inactivated spores from avirulent Bacillus cereus strains provides significant protection from challenge with Bacillus anthracis Ames.  Clin Vaccine Immunol. 20:56-65.  PMID: 23114705.

6.        Simon, N.C., J.M. Vergis, A.V. Ebrahimi, C.L. Ventura, A.D. O'Brien, and J.T. Barbieri.  2013.  Host cell cytotoxicity and cytoskeleton disruption by CerADPr, an ADP-ribosyltransferase of Bacillus cereus G9241.  Biochem.  52:2309-18.  PMID: 22934824.

7.        Zangari, T., Melton-Celsa, A.R., Panda, A., Boisen, N., Smith, M. A., Taratov, I., Detolla, L., Nataro, J., O’Brien, A.D. 2013. Virulence of the Shiga toxin type 2-expressing Escherichia coli O104:H4 German outbreak isolate in two animal models. Infec. Immun. 81(5):1562-74.  PMID: 23439303.

8.        Flora, A. D., Teel, L.D., Smith, M.A., Sinclair, J.F., Melton-Celsa, A.R., O’Brien, A.D. 2013. Ricin crosses polarized human intestinal cells and intestines of ricin-gavaged mice without evident damage and then disseminates to mouse kidneys.  PLoS One. 8(7):e69706.  PMID: 23874986.

9.        Zumbrun, S.D., Melton-Celsa, A.R., Smith, M.A., Gilbreath, J.J., Merrell, D.S., O’Brien A.D. 2013. Dietary choice affects Shiga toxin-producing Escherichia coli (STEC) O157:H7 colonization and disease. Proc. Natl. Acad. Sci. USA. 110(23):E2126-33.  PMID: 23690602.

10.     Bunger, J.C., A.R. Melton-Celsa, and A.D. O’Brien.  2013.  Shiga toxin type 2dact displays increased binding to globotriaosylceramide in vitro and increased lethality in mice after activation by elastase.  Toxins.  5:2074-2092.  PMID: 24217397.

11.     Russo, L.M., A.R. Melton-Celsa, and A.D. O’Brien.  2014.  Oral intoxication of mice with Shiga toxin type 2a (Stx2a) and protection by anti-Stx2a monoclonal antibody 11E10.  Infect. Immun.  82(3):1213-21.  PMID: 24379294.

12.     Russo, L.M., A.R. Melton-Celsa, M.J. Smith, and A.D. O’Brien.  2014.  Comparisons of native Shiga toxins (Stxs) type 1 and 2 with chimeric toxins indicate that the source of the binding subunit dictates degree of toxicity.  PLoS One.  9(3):e93463.  PMID: 24671194.

13.     Boisen, N., A.-M. Hansen, A.R. Melton-Celsa, T. Zangari, N.P. Mortensen, J.B. Kaper, A.D. O’Brien, and J.P. Nataro.  2014.  The presence of the pAA plasmid in the German O104:H4 Shiga toxin (Stx) type 2a-producing enteroaggregative Escherichia coli strain promotes the translocation of Stx2a across an epithelial cell monolayer.  J. Infect. Dis.  210(12):1909-19.  PMID: 25038258.

14.     Zangari, T., A.R. Melton-Celsa, M.A. Smith, and A.D. O’Brien.  2014.  Enhanced virulence of the Escherichia coli O157:H7 spinach-associated outbreak strain in two animal models is associated with higher levels of Stx2 production after induction with ciprofloxacin.  Infect Immun.  82(12):4968-77.  PMID: 25225244.

15.     O’Neill, K.M., A.M. Schilthuis, C.A. Leiter, K.M. Neihaus, N.A. Judge, E. Twiddy, A.D. O’Brien, and W.R. Curtis.  2015.  Scale-up of transgenic tobacco cells that express intimin of enterohemorrhagic Escherichia coli O157:H7 for use as an oral vaccine in cattle.  In Vitro Cell Develop Biol – Plant.  In Press.

16.     Smith, M.A., R.A. Weingarten, L.M. Russo, C.L. Ventura, and A.D. O’Brien.  2015.  Antibodies against Hemolysin and Cytotoxic Necrotizing Factor type 1 (CNF1) reduce bladder inflammation in a mouse model of urinary tract infection with toxigenic uropathogenic Escherichia coli.  Infect Immun.  83(4):1661-73.  PMID: 25667267.

17.     Melton-Celsa, A.R., H.M. Carvalho, C. Thuning-Roberson, and A.D. O’Brien.  2015.  Protective efficacy and pharmacokinetics of human/mouse chimeric anti-Stx1 and anti-Stx2 antibodies in mice.  Clin Vacc Immunol.  22:448-55.  PMID: 25716230.

18.     Pock, A.R., M. Ottolini, L.N. Pangaro, W.R. Gilliland, B.V. Reamy, P.A. Hemmer, M. Stephens, A. O’Brien, and L. Laughlin.  2015.  Academic change management: leadership lessons from curricular reform.  Mil Med.  180(4):160-162.  PMID: 25850145.

19.     Melton-Celsa, A.R., A.D. O’Brien, and P.C.H. Feng.  2015.  Virulence potential of Shiga toxin 2dact-producing Escherichia coli isolated from fresh produce.  J Food Protect.  78:2085-2088. PMID: 26555533.

20.     Bunger, J.C., A.R. Melton-Celsa, E.L. Maynard, and A.D. O’Brien.  2015.  Reduced toxicity of Shiga toxin (stx) Type 2c in mice compared to Stx2d is associated with instability of Stx2x holotoxin.  Toxins.  7:2306-2320.   PMID: 26110507. 

21.     Russo, L.M., N.F. Abdeltawab, A.D. O’Brien, M. Kotb, and A.R. Melton-Celsa.  2015.  Mapping of genetic loci that modulate differential colonization by Escherichia coli O157:H7 TUV86-2 in advanced recombinant inbred BXD mice.  BMC Genomics.  16:947.  PMID: 26573818.

22.     Russo, L.M., A.R. Melton-Celsa, and A.D. O’Brien.  2015.  Shiga toxin type 1a (Stx1a) reduces the oral toxicity of Stx2a.  J. Infect. Dis.  213(8):1271-1279.  PMID: 26743841

23.     Scarff, J.M., M.J. Raynor, Y.I. Seldina, C.L. Ventura, T.M. Koehler, and A.D. O’Brien.  2016.  The roles of AtxA orthologs in virulence of anthrax-like Bacillus cereus G9241.  Mol Microbiol.  doi: 10.1111/mmi.13478. PMID: 27490458