Patricia Ferrieri, M.D.

Professor, Pediatrics and Laboratory Medicine and Pathology
Director, Clinical Microbiology Laboratory
Mayo Mail Code 134
420 Delaware Street SE
Minneapolis, MN 55455
Phone: (612) 624-1948
Fax: (612) 624-8927
ferri002@umn.edu

Dr. Patricia Ferrieri's laboratory is focused on the pathogenesis of infections with group B streptococci (GBS) and host immunity to streptococcal antigens. These investigations have included the epidemiology of maternal and neonatal colonization and infection with GBS, animal models of neonatal sepsis and meningitis, isolation and biochemical and immunological characterization of key antigens of group B streptococci, and human and animal immune responses to these antigens, including the role of monoclonal and polyclonal antibodies in protection against infection. Her laboratory has cloned the gene for a key surface localized protein (glutamine synthetase) of GBS into E. coli, and has used polymerase chain reaction (PCR) technology and nucleotide sequencing and amino acid sequencing of this GBS protein to enhance the research.

Key areas of research include:

1. Neonatal sepsis and meningitis has been a sustained interest of Dr. Ferrieri. Laboratory approaches include epidemiologic- bacteriologic- immunologic studies. Experimental models of bacteremia and meningitis in neonatal rats have been established using the various serotypes of GBS, as well as K1 and non-K1 E. coli strains.
2. Animal models of colonization with streptococci, including group A streptococci, group B streptococci, and Haemophilus influenzae, have been developed to pursue bacterial adherence in vivo, and bacterial adherence to epithelial cells has been studied in vitro.
3. Biochemical and immunological studies of GBS constituents - the focus has been on protein antigens, including characterization of an intracellular enzyme hippuricase, distinct extracellular deoxyribonucleases, a cell-associated hemolysin of GBS and the surface-localized proteins, including the a and b components of the c protein antigen and the R protein antigens. The interaction of GBS with the complement pathways has been pursued, and further studies are planned when genetic mutants of GBS are produced.
4. Comparisons of the surface-localized proteins and prevalence of antibodies in human sera. These surface localized proteins are present in the vast majority of GBS serotypes, including those associated with neonatal sepsis and meningitis. The R protein antigen is commonly found on type II and type III strains, and antibody is prevalent in maternal and infant sera. Further studies include electron microscopy to localize the protein antigens of GBS and examination of the protective functional activity of antibodies to the R proteins by in vivo studies in the infant rat model, as well as studies of in vitro phagocytosis and killing.
5. Surface localized GBS proteins are being studied, such as R4 and R5, by gene sequencing and are being examined for other biologic properties.
6. Multinational GBS initiative to develop strategies for prevention of GBS disease. Dr. Ferrieri's research laboratory has been funded for another 5 years (1997-2002) to serve as the molecular reference laboratory for research being conducted by Dr. Dennis Kasper in Boston, Dr. Carol Baker in Houston, and investigators in Pittsburgh. The studies of Dr. Ferrieri and others of the surface-localized proteins have additional value because of the consideration of including these proteins as conjugates in GBS polysaccharide vaccines.
7. Molecular epidemiologic work has included the restriction enzyme analysis of GBS isolates of all serotypes, demonstrating marked genetic diversity among the different serotypes and within each serotype. This information is valuable in pursuing studies of clusters of disease in nurseries or intensive care units. Molecular studies of nosocomial vancomycin resistant enterococcal strains are under study including the vanA gene by Southern analysis and PFGE profiles.

Dr. Ferrieri is also the Medical Director of the Clinical Microbiology Laboratory of the University of Minnesota Medical Center, Fairview. Fellows acquire experience in bacteriology, antibiotics, mycology, and parasitology, including the use of DNA and monoclonal antibody probes and PCR technology in diagnostic microbiology.

Selected Recent Publications

• Nizet V, Ferrieri P, Rubens CE: Molecular pathogenesis of group B streptococcal disease in newborns. In: Streptococcal Infections, DL Stevens and EL Kaplan, eds. Oxford University Press, New York. p. 180-221, 2000. 
• Zaleznik DF, Rench MA, Hillier S, Krohn MA, Platt R, Lee M-LT, Flores AE, Ferrieri P, Baker CJ: Invasive group B streptococcal disease in pregnant women and neonates from diverse population groups. Clin Infect Dis. 30:276-281, 2000. 
• Tamura GS, Herndon M, Przekwas J, Rubens CE, Ferrieri P, Hillier S: Analysis of restriction fragment length polymorphisms of the insertion sequence IS1381 in group B streptococci. J Infect Dis. 181:364-368, 2000. 
• Flores AE, Erdogan S, Chhatwal GS, Baker CJ, Hillier S, Ferrieri P: Expression of the R5 surface protein among polysaccharide serotypes of group B streptococci. Proceedings of the XIV Lancefield International Symposium on Streptococci and Streptococcal Diseases, Oct. 11-15, 1999, Auckland, New Zealand. In: Streptococci and Streptococcal Diseases Entering the New Millennium. DR Martin and JR Tagg, eds. Securacopy, Auckland, New Zealand. p. 191-194, 2000. 
• Benson JA, Flores AE, Baker CJ, Hillier S, Ferrieri P: Upregulation of polysaccharide expression and pulsed-field gel electrophoresis characterization of nontypeable group B streptococcal isolates. Proceedings of the XIV Lancefield International Symposium on Streptococci and Streptococcal Diseases, Oct. 11-15, 1999, Auckland, New Zealand. In: Streptococci and Streptococcal Diseases Entering the New Millennium. DR Martin and JR Tagg, eds. Securacopy, Auckland, New Zealand. p. 185-189, 2000. 
• Smith BL, Ferrieri P: Indentification, conservation, and suggested immunogenicity of GBbcA, a group B streptococcal surface protein that binds complement protein C3. Proceedings of the XIV Lancefield International Symposium on Streptococci and Streptococcal Diseases, Oct. 11-15, 1999, Auckland, New Zealand. In: Streptococci and Streptococcal Diseases Entering the New Millennium. DR Martin and JR Tagg, eds. Securacopy, Auckland, New Zealand. p. 649-652, 2000. 
• Campbell JR, Hillier SL, Krohn MA, Ferrieri P, Zaleznik DF, Baker CJ: Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery. Obstetrics and Gynecology. 96:489-503, 2000. 
• Benson JA, Ferrieri P: Rapid pulsed-field gel electrophoresis method for group B Streptococcus isolates. J Clin Microbiol. 39:3006-3008, 2001. 
• Baker CJ, Carey VJ, Edwards MS, Ferrieri P, Hillier SL, Krohn MA, Guttormsen H-K, Kasper DL, Platt R: Serologic determinants of neonatal group B streptococcal disease. Submitted for publication. 
• Benson JA, Flores AE, Baker CJ, Hillier S, Ferrieri P: Improved methods for typing nontypeable isolates of group B streptococci. Submitted for publication.