Scott Weissman, MD
Assistant Professor of Pediatric Infectious Diseases
Email: click here
Phone: (206) 884-1067
Despite being one of the most exhaustively studied free-living organisms in biology, the Escherichia coli bacterium continues to produce a massive burden of disease, including extraintestinal syndromes such as urinary tract infections (UTI) and bloodstream infections. Since the initiation of intrapartum antimicrobial prophylaxis for group B streptococcus during pregnancy,E. coli has become the leading bacterial cause of early-onset sepsis (EOS) in newborns. Now, with ampicillin-resistant rates >80% amongE. coliisolates, it remains unclear whether contemporary EOS isolates represent antibiotic-resistant derivatives of the traditional K1-encapsulated clones described in the 1970’s (which would facilitate rapid point-of-care screening tests) or a more diverse array of novel antibiotic-resistant clones like those that have complicated empiric treatment of community-acquired UTI (e.g., Bactrim-resistant ‘clonal group A’). Dr. Weissman and his lab use PCR- and sequence-based molecular typing techniques to characterize clinical isolate collections gathered through active and passive surveillance by the NICHD Neonatal Research Network and the Minnesota Department of Health. With the appearance of EOS-associated clones resistant to standard ampicillin/gentamicin combination therapy, this project will inform guidelines for the empiric treatment of early-onset sepsis. His lab is also using molecular techniques to characterize the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL) enzymes among Enterobacteriaceae. Since 2000, they have witnessed the worldwide emergence of Gram-negative ‘superbugs’ such as E. coli ST131 andKlebsiella pneumonia ST258—which not only encode multiple virulence factors associated with extraintestinal disease, but also Class A enzymes that hydrolyze third-generation cephalosporins and carbapenem antibiotics (CTX-M-15 and KPC, respectively). Their molecular typing methods will characterize the dynamics of antibiotic resistance, to distinguish epidemics of resistance genes that spread between plasmids, plasmids that spread between strains, and strains that spread across continents.
Yale University, B.A., Psychology, 1990
Yale University, Post-baccalureate study in pre-medicine, 1990-91
University of California, Irvine, College of Medicine, 1997
Kaiser Foundation Hospital, Los Angeles, 1997-2000
Children's Hospital and Regional Medical Center/University of Washington, 2000-03
Chattopadhyay S, Weissman SJ, Minin VN, Russo TA, Dykhuizen DE, Sokurenko EV (2009). High frequency of hotspot mutations in core genes of Escherichia coli due to short-term positive selection. Proc Natl Acad Sci USA 106(30):12412-7.
Qin X, Zerr DM, Weissman SJ, Englund JA, et al (2008). Prevalence and mechanisms of broad-spectrum beta-lactam resistance in Enterobacteriaceae: a children's hospital experience.
Antimicrob Agents Chemother 52(11):3909-14.
Weissman SJ, Beskhlebnaya V, Chesnokova V, Chattopadhyay S, Stamm WE, Hooton TM, Sokurenko EV (2007). Differential stability and trade-off effects of pathoadaptive mutations in the Escherichia coli FimH adhesin. Infect Immun 75(7):3548-55.
Chattopadhyay S, Feldgarden M, Weissman SJ, Dykhuizen DE, van Belle G, Sokurenko EV (2007). Haplotype diversity in "source-sink" dynamics of Escherichia coli urovirulence. J Mol Evol 64(2):204-14.
Weissman SJ, S Chattopadhyay, P Aprikian, M Obata-Yasuoka, Y Yarova-Yarovaya, A Stapleton, W Ba-Thein, D Dykhuizen, JR Johnson, and EV Sokurenko (2006). Clonal analysis reveals high rate of structural mutations in fimbrial adhesins of extraintestinal pathogenic Escherichia coli. Mol Micro 59(3):975-988.
Johnson JR, Owens KL, Clabots CR, Weissman SJ, Cannon SB (2006). Phylogenetic relationships among clonal groups of extraintestinal pathogenic Escherichia coli as assessed by multi-locus sequence analysis. Microbes Infect 8(7):1702-13.
Sokurenko EV, M Feldgarden, E Trintchina, SJ Weissman, S Avagyan, S Chattopadhyay, JR Johnson, and DE Dykhuizen (2004). Selection footprint in the FimH adhesin shows pathoadaptive niche differentiation in Escherichia coli. Mol Biol Evol 21(7):1373-1383.
Qin X, SJ Weissman, MF Chesnut, B Zhang, and L Shen (2004). Kirby-Bauer Disc approximation to detect inducible third-generation cephalosporin resistance in Enterobacteriaceae. Ann Clin Micro Antimicrob 3:13.
Weissman SJ, SL Moseley, DE Dykhuizen, and EV Sokurenko (2003). Enterobacterial adhesins and the case for studying SNPs in bacteria. Trends Micro 11(3):115-117.
Johnson JR, Weissman SJ, Stell AL, Trintchina E, Dykhuizen DE, Sokurenko EV (2001). Clonal and pathotypic analysis of archetypal Escherichia coli cystitis isolate NU14. J Infect Dis 184(12):1556-65.
Badger JL, Wass CA, Weissman SJ, Kim KS (2000). Application of signature-tagged mutagenesis for identification of Escherichia coli K1 genes that contribute to invasion of human brain microvascular endothelial cells. Infect Immun 68(9):5056-61.