Patrick C. Seed, MD, PhD

Department / Division:
Pediatrics / Infectious Diseases

Address:
DUMC 2808
Durham, NC 27710

Appointment Telephone:
919-668-4000

Office Telephone:
919-684-9590

Fax Telephone:
919-681-2089

• MD, University of Rochester School of Medicine and Dentistry (New York), 1998

• Pediatrics, University of Michigan, 1998-2002

• Pediatric Infectious Diseases, Washington University (Missouri), 2002-2005

• PhD, Microbiology and Immunology, University of Rochester (New York), 1998

Clinical Interests:
Pediatric infectious disease, complex infections of hospitalized children, urinary tract infections (acute, chronic, and recurrent)

Research Interests:
Uropathogenic Escherichia coli (UPEC) are the leading cause of community-acquired urinary tract infections (UTIs).  Over 100 million UTIs occur annually throughout the world including more than 7 million in U.S. adolescents and adults and result in billions of health care dollars.  UTIs in younger children are associated with greater risk of morbidity and mortality than in older children and adults.  Neonates have increased risk of urosepsis and meningitis.  Febrile UTIs in children under 5 years  frequently represent pyelonephritis which results in renal scarring in 27 to 64% cases in the absence of underlying urinary tract anomalies and can lead to hypertension and chronic renal failure.

Recurrent UTI causes additional morbidity.   Over 25% of women with an initial UTI experience recurrent infections, and  most occur within the first 6 months after the initial infection.    Up to 70% of young children with UTI develop at least 1 recurrence, putting them at a higher risk for renal scarring. Most studies have shown that over 40-60% of the recurrent UPEC are the sa me isolate as caused the initial UTI.

The pathogenesis of bladder infection (cystitis) in a mouse model closely mimicks human infection.  UPEC adhere, invade, and amass in the superficial epithelial cells of the bladder.  The biomasses of bacteria, called intracellular bacterial communities (IBC), have biofilm-like characteristics, making this a great model of in vivo biofilm formation.  These first three steps in pathogenesis rely on the adhesive pilus structure called type 1 pili.  After IBC formation, the bacteria disperse and flux from infected cells where they re-adhere and invade new epithelial cells.  In mice, we observe that bacteria can also enter into a chronic persistent state and reemerge to produce further episodes of bacteruria months later.

Using a cutting-edge combination of microbial genetics, molecular biology, advanced microscopy, biochemistry, immunology, and animal modeling, we are exploring how UPEC interacts with the bladder epithelium to persist during acute and chronic infections.  We have shown that intracellular proliferation in IBC is a key step in pathogenesis and, as a consequence, are exploring the regulation and contribution of key virulence factors in the initiation and development of the IBC state.  We are also exploring how discrete members of bacterial populations enter into productive niches while other subpopulations fail to persist resulting in profound population bottlenecks.  Last, we are mapping the ligand-receptor bacterial-host temporal spatial changes that occur as a consequence of bladder infections.    Perhaps most importantly, we are collaborating with clinical experts in urinary tract infections to create a reciprocal exchange of ideas and observations.  Through these collaborations, we aim to use key clinical observations and human specimens to shape our molecular research (bedside to bench) and translate some of the molecular details of UTI discovered in the laboratory into new diagnostics and therapies (bench to bedside).

Representative Publications:
Hannan TJ, Mysorekar IU, Chen SL, Walker JN, Jones JM, Pinkner JS, Hultgren SJ, Seed PC. LeuX tRNA-dependent and -independent mechanisms of Escherichia coli pathogenesis in acute cystitis.  Mol Microbiol.  2008 Jan;67(1):116-28. (2008) Abstract

Wright KJ, Seed PC, Hultgren SJ. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili.  Cell Microbiol.  2007 Sep;9(9):2230-41. (2007) Abstract

Uhlmann EJ, Seed PC, Schwan TG, Storch GA. Tick-borne relapsing fever polymerase chain reaction of tick-borne relapsing fever caused by Borrelia hermsii.  Pediatr Infect Dis J.  2007 Mar;26(3):267-9. (2007) Abstract

Lenfestey RW, Smith PB, Moody MA, Clark RH, Cotten CM, Seed PC, Benjamin DK Jr. Predictive value of cerebrospinal fluid parameters in neonates with intraventricular drainage devices.  J Neurosurg.  2007 Sep;107(3 Suppl):209-12. (2007) Abstract

Pinkner JS, Remaut H, Buelens F, Miller E, Aberg V, Pemberton N, Hedenström M, Larsson A, Seed P, Waksman G, Hultgren SJ, Almqvist F. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17897-902. (2006) Abstract

Justice SS, Hunstad DA, Seed PC, Hultgren SJ. Filamentation by Escherichia coli subverts innate defenses during urinary tract infection.  Proc Natl Acad Sci U S A.  2006 Dec 26;103(52):19884-9. (2006) Abstract

Elward A, Grim A, Schroeder P, Kieffer P, Sellenriek P, Ferrett R, Adams HC, Phillips V, Bartow R, Mays D, Lawrence S, Seed P, Holzmann-Pazgal G, Polish L, Leet T, Fraser V. Outbreak of Salmonella javiana infection at a children's hospital. Infect Control Hosp Epidemiol. 2006 Jun;27(6):586-92. (2006) Abstract

Wright KJ, Seed PC, Hultgren SJ. Uropathogenic Escherichia coli flagella aid in efficient urinary tract colonization. Infect Immun. 2005 Nov;73(11):7657-68. (2005) Abstract

Seed PC, Hultgren SJ. Blueprinting the regulatory response of Escherichia coli to the urinary tract. Trends Microbiol. 2005 Jun;13(6):246-8. (2005) Abstract

de Kievit T, Seed PC, Nezezon J, Passador L, Iglewski BH. RsaL, a novel repressor of virulence gene expression in Pseudomonas aeruginosa. J Bacteriol. 1999 Apr;181(7):2175-84. (1999) Abstract

Preston MJ, Seed PC, Toder DS, Iglewski BH, Ohman DE, Gustin JK, Goldberg JB, Pier GB. Contribution of proteases and LasR to the virulence of Pseudomonas aeruginosa during corneal infections. Infect Immun. 1997 Aug;65(8):3086-90. (1997) Abstract

Pesci EC, Pearson JP, Seed PC, Iglewski BH. Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa. J Bacteriol. 1997 May;179(10):3127-32. (1997) Abstract

Seed PC, Passador L, Iglewski BH. Activation of the Pseudomonas aeruginosa lasI gene by LasR and the Pseudomonas autoinducer PAI: an autoinduction regulatory hierarchy. J Bacteriol. 1995 Feb;177(3):654-9. (1995) Abstract