Thomas A. Russo, M.D. Assistant Professor Department of Medicine Phone: (716) 829-2674 Fax: (716) 829-2158 Email: trusso@buffalo.edu

Overview of the Laboratory

Ongoing Projects:
Our laboratory is interested in further understanding the pathogenesis of infections due to extraintestinal isolates of E. coli. This information will be critical for the logical development of new preventative and/or therapeutic strategies. A bacteremic strain (CP9, (O4/K54/H5) is being used as a model pathogen. Ongoing projects include:

1) Identification and evaluation of their role in the pathogenesis of infection of genes required for growth and survival in urine, ascites, and blood

2) Identification and evaluation of their role in the pathogenesis of infection of genes with increased expression in vivo

3) Identification of antigenic determinants expressed in vivo and their evaluation as potential vaccine candidates

4) Increase our understanding of Gram-negative pneumonia via:

a) Establishing the relative importance of bacterial products versus host factors in meditating pulmonary damage.
b) Evaluate the role of bacterial traits (other than lipid A) in modulating host defense responses.
c) Evaluate the effects of E. coli pneumonitis on specific host targets (e.g. surfactant).

5) Molecular epidemiology of infections due to extraintestinal strains of E. coli.

Collaborators:
Dr. James Johnson:
Medical Service, VA Medical Center, and Department of Medicine, University of Minnesota, Minneapolis, Minnesota.

Infection models , Molecular epidemiology
Dr. Paul Knight:
Dr. Bruce Holm:
Bruce Davidson:
Roger Priore:
Department of Microbiology, The Witebsky Center for Microbial Pathogenesis and Immunology, Department of Anesthesiology, Department of Pediatrics, and the Department of Social and Preventive Medicine, State University of New York, Buffalo, New York
Gram-negative pneumonia

Professional Activities:

2005 Top 100 Princeipal Investigators at the University at Buffalo

Relevant Publications:

1. Russo, TA., Guenther, JE., Wenderoth, S. and Frank, MM. 1993. Generation of isogenic K54 capsule deficient Escherichia coli strains through TnphoA mediated gene disruption. Molec. Microbiol. 9:357-364

2. Russo, TA., Moffitt, MC., Hammer, CH. And Frank, MM. 1993. TnphoA mediated disruption of K54 capsular polysaccharide genes in Escherichia coli confers serum sensitivity. Infect. Immun. 61:3578-3582

3. Russo, TA. And Singh, GJ 1993. An extra-intestinal, pathogenic isolate of Escherichia coli (O4/K54/H5) can produce a group 1 capsule which is divergently regulated from its constitutively produced group 2, K54 capsular polysaccharide. J. Bacteriol. 175:7617-7623

4. Russo, TA., Liang, Y. and Cross, AS. 1994. The presence of K54 capsular polysaccharide increases the pathogenicity of Escherichia coli in vivo. J. Infect. Dis. 169:112-118

5. Russo, TA., Sharma, G., Brown,CR and Campagnari, AA. 1995. The loss of the 04 antigen moiety from the lipopolysaccharide of an extraintestinal Isolate of E. coli has only minor effects on serum sensitivity and virulence in vivo. Infect. Immun. 63:1263-1269

6. Russo, TA., Sharma, G., Weiss, J., and Brown, C. 1995. The construction and characterization of colanic acid deficient mutants in an extraintestinal isolate of Escherichia coli (O4/K54/H5). Microb. Pathog. 18:269-278

7. Russo, TA., Stapleton, A., Wenderoth, S., Hooton, TM., Stamm, WE. 1995 A chromosomal RFLP Analysis of E. coli strains causing recurrent urinary tract infections in young women. J. Infect. Dis. 172:440-445

8. Russo, TA., Brown, JJ, Jodush, ST., and Johnson, JR. 1996. The O4 specific antigen moiety of lipopolysaccharide but not the K54 group 2 capsule is important for urovirulence in an extraintestinal isolate of Escherichia coli. Infect. Immun. 64: 2343-2348

9. Russo, TA., Jodush, ST., Brown, JJ. And Johnson, JR. 1996. Identification of two previously unrecognized genes (guaA, argC) important for uropathogenesis. Molec. Microbiol. 22:217-229

10. Johnson, JR., Russo,TA., Scheutz, F., Brown, JJ., Zhang, L., Palin, K., Rode, C., Bloch, C., Marrs, CF. and Foxman, B. 1997. Discovery of a disseminated J96-like clone of uropathogenic Escherichia coli 04:H5 containing both papGJ96 (AClass I@) and prsGJ96 (AClass III@) Gal(alphal-4)Gal-binding adhesion sequences. J. Infect. Dis. 175:983-988

11. Johnson, JR., Stapleton,AE., Russo,TA., Scheutz, F., Brown, JJ., and Maslow, JN. 1997 Characteristics and prevalence within serogroup O4 of a J96-like clonal group of uropathogenic Escherichia coli O4:H5 containing the Class I and Class III alleles of papG. Infect. Immun. 65:2153-2159

12. Johnson, JR., Russo, TA., Brown, JJ., Stapleton, A. 1998 papG alleles of Escherichia coli first-episode or recurrent acute cystitis in adult women. J. Infect. Dis. 177:97-101

13. Russo, TA., Wenderoth, S., Carlino UB., Merrick, JM., Lesse, AJ. 1998 Identification genomic organization and analysis of the Group III capsular polysaccharide genes kpsD, kpsM, kpsT, and kpsE from an extraintestinal isolate of Escherichia coli (CP9, 04/K54/H5) J. Bacteriol. 180:338-349

14. Johnson, JR., Brown, JJ., Carlino, UB., Russo, TA 1998 Colonization with and acquisition of uropathogenic Escherichia coli as revealed by polymerase chain reaction-based detection. J. Infect. Dis. 177:1120-1124

15. Russo, TA., Mylotte, D. 1998 Expression of the K54 and O4 specific antigen have opposite effects on the bactericidal activity of squalamine against an extraintestinal isolate of E. coli FEBS Microbiol. Lett. 162:311-315

16. Russo,TA., Carlino, UB., Mong, A., Jodush, ST. 1999 Identification of genes in an extraintestinal isolate of Escherichia coli with increased expression after exposure to human urine. Infect. Immun. 67:5306-5314

17. Johnson, JR., Stell, A., Scheutz, F., O’Bryan, TT., Russo, TA., Carlino, U., Fasching, C., Kavle, J., Van Dijk, L., Gaastra, W. 2000 Analysis of the F antigen-specific alleles of extraintestinal pathogenic Escherichia coli using a novel multiplex polymerase chain reaction-based assay. Infect, Immun. 68:1587-1599

18. Russo, TA., Davidson, B., Prior, R., Carlino, UB., Helinski, J., and Knight, P. III 2000 Capsular Polysaccharide and O-Specific Antigen Divergently Modulate Pulmonary Neutrophil Influx in a Rat Escherichia coli Model of Gram-Negative Pneumonitis. Infect. Immun. 68:2854-2862

19. Russo, TA., and Johnson, JR. 2000 A proposal for a new inclusive designation for extraintestinal pathogenic isolates of Escherichia coli: (ExPEC). J.Infect.Dis. 181:1753-1754

20. Johnson, JR., Russo, TA., Tarr, PI., Carlino, U., Bilge, SS., Vary, JC., and Stell, AL. 2000 Divergent associations of two novel virulence genes of extraintestinal pathogenic Escherichia coli (ExPEC), iha and iroNE.coli, with other virulence genes, phylogenetic groups, antimicrobial resistance and host compromise. Infect. Immun. 68:3040-3047

21. Johnson, JR., O'Bryan, TT., Low, DA., Ling, G., Delavari, P., Fasching, C., Russo, TA., Carlino, U., and Stell, AL. 2000 Evidence of Commonality between Canine and Human Extraintestinal Pathogenic Escherichia coli that Express PapG Allele III.. Infect. Immun. 68:3327-3336

22. Johnson, JR., Delavari, P., Stell, AL., Whittam, TS., Carllino, U., Russo, TA. 2001. Comparison of extraintestinal Escherichia coli Isolates from the same electrophoretic lineages from humans and domestic animals J. Infect. Dis. 183:154-159

23. Johnson JR, Delavari P, Stell AL, Prats G, Carlino U, Russo TA. 2001. On theintegrity of archival strain collections, including the ECOR collection. ASM News June pp. 288-2289.

24. Johnson, JR., O,Bryan, TT., Delavari, P., Kuskowski, M., Stapleton, A., Carlino, U., Russo, TA. 2001. Clonal relationships and extended virulence genotypes among Escherichia coli isolates from women with first episode or recurrent cystits. J. Infect. Dis. 183:1508-1517

25. Russo, TA, Carlino, UB, Johnson, JR, 2001. Identification of ireA, a new iron regulated virulence gene in an extraintestinal pathogenic isolate of Escherichia coli. Infect. Immun. 69: 6209-6216

26. Johnson, Russo, TA. Extraintestinal pathogenic Escherichia coli (ExPEC): the "Other Bad E. coli:. 2002 J. Lab Clin. Med. 139:155-162

27. Russo, TA, Bartholomew, LA, Davidson, BA, Helinski, JD, Carlino, UB, Knight III, PR, Beers, MF, Athochina, EN., Notter, RH, and Holm, BA. Total extracellular surfactant is increased but abnormal in ia rat model of gram-negativebacterial pneumonitis. American J. Physiol. -Lung Cell. Molec. Physiol. In Press.

28. Johnson, JR., and Russo, TA. "Uropathogenic" Escherichia coli as Agents of Diverse Non-Urinary-Tract Extraintestinal Infection. J. Infect. Dis. In Press.

29. .Davidson BA, Stewart CC, Russo TA, Chess PR, Notter RH, Knight PR. Discrimination of resident and infiltrated alveolar macrophages in influenza A virus-infected mice. 2005 Exp. Lung Res. 31:323-339

30. Davidson BA, Knight PR, Wang Z, Chess PR, Holm BA, Russo TA, Hudson A, Notter, RH. Surfactant alterations in acute inflammatory lung injury from aspiration of acid and gastric particulates. 2005 American J. Physiol.-Lung Cell. Molec. Physiol 288:L699-708

31 Russo, TA, Davidson, BA, Genagon, SA, Warholic, NM, MacDonald, U, Pawlicki, PD, Beanan, JM, Olson, R, Holm, BA, and Knight, PR III. E. coli virulence factor hemolysin induces apolptosis and necrosis/lysis in vitro and necrosis/lysis and lung injury in a rat pneumonia model. 2005: Am. J. Physiol.-Lung Cell Mol. Physiol. 289:L207-216

32. Raghavendran K, Davidson BA, Mullan BA, Hutson AD, Russo TA, Manderscheid PA, Woytash JA, Holm BA, Notter RH, Knight PR. Acid and Particulate-induced Aspiration Lung Injury In Mice: Importance of MCP-1(Macrophage Chemoattractant Protein-1). 2005 Am J Physiol Lung Cell Mol Physiol. 289:L134-43. Epub 2005 Mar 18

33. Johnson, JR and Russo, TA. Molecular epidemiology of extraintestinal (uropathogenic) Escherichia coli . 2005 Int. J. Med. Microbiol. 295:383-404.

34. Russo, TA and Johnson, JR. Extraintestinal isolates of E. coli : identification and prospects for vaccine development. 2006 Expert Rev. of Vaccines. 5:45-54

35. Russo TA. Wang Z. Davidson BA. Genagon SA. Beanan JM. Olson R. Holm BA. Knight PR 3rd. Chess PR. Notter RH. Surfactant dysfunction and lung injury due to the E. coli virulence factor hemolysin in a rat pneumonia model. American Journal of Physiology - Lung Cellular & Molecular Physiology. 292(3)::632-43, 2007 Mar.

36. Segal BH. Davidson BA. Hutson Ad. Russo TA. Holm BA. Mullan B. Habitzruther M. Holland SM. Knight PR 3rd. Acid aspiration-induced lung inflammation and injury are exacerbated in NADPH oxidase-deficient mice. American Journal of Physiology - Lung Cellular & Molecular Physiology. 292(3):L760-8, 2007 Mar.

37. Russo TA. Johnson JR. Extraintestinal isolates of Escherichia coli: identifcation an dprospects for vaccine development. [Review] [98 refs] Expert Review of Vaccines. 5(1):45-54, 2006 Feb.

28. Nazareth H. Genagon SA. Russo TA. Extraintestinal pathogenic Escherichia coli survives within neutrophils.In fection & Immunity. 75(6):2776-85, 2007 Jun.

39. Russo TA Beanan JM. Olson R. Genagon SA. MacDonald U. Cope JJ. Davidson BA. Johnston JR. A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate. Vaccine. 25(19):3859-70, 2007 May 10.

Clinical Chapters

1. Russo, TA.: Agents of Actinomycosis. In: Mandell, GL., Bennett, JE. and Dolin, R., Eds. Principes and Practice of Infectious Diseases , 6 th Ed., 2005 p.2924-2934

2. Johnson, J. R., and T. A. Russo [ date of posting online ]. Module 8.6.1.4.: Molecular epidemiology of extraintestinal pathogenic Escherichia coli . In R. Curtiss III (Editor in Chief), EcoSal: Escherichia coli and Salmonella : Cellular and Molecular Biology. http://www.ecosal.org <http://www.ecosal.org/ In Press

3. Russo, TA.: Actinomycosis. In: Fauci, AS, Braunwald, E , Kasper, DL, .Hauser, SL., Longo, DL., Jameson, JL., Loscalzo, J. Eds. Harrison's Principles of Internal Medicine , 17 th Ed. In Preparation

4. Russo, TA.: Diseases Caused by Gram-Negative Enteric Bacilli. In: Fauci, AS, Braunwald, E Kasper, DL, .Hauser, SL., Longo, DL., Jameson, JL., Loscalzo, J. Eds. Harrison's Principles of Internal Medicine , 17 th Ed., In Preparation