Deborah Dee Jaworski
University of Michigan
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Deborah Dee Jaworski.
Trends in Microbiology | 1995
Don B. Clewell; Susan E. Flannagan; Deborah Dee Jaworski
Conjugative transposons are highly ubiquitous elements found throughout the bacterial world. Members of the Tn916-Tn1545 family carry the widely disseminated tetracycline-resistance determinant Tet M, as well as additional resistance genes. They have been found naturally in, or been introduced into, over 50 different species and 24 genera of bacteria. Recent investigations have led to insights into the molecular basis of movement of these interesting mobile elements.
Antimicrobial Agents and Chemotherapy | 2002
David J. Payne; William H. Miller; Valerie Berry; John Brosky; Walter J. Burgess; Emile Chen; Walter E. DeWolf; Andrew Fosberry; Rebecca Greenwood; Martha S. Head; Dirk A. Heerding; Cheryl A. Janson; Deborah Dee Jaworski; Paul M. Keller; Peter J. Manley; Terrance D. Moore; Kenneth A. Newlander; Stewart Pearson; Brian J. Polizzi; Xiayang Qiu; Stephen Rittenhouse; Courtney Slater-Radosti; Kevin L. Salyers; Mark A. Seefeld; Martin G. Smyth; Dennis T. Takata; Irene Nijole Uzinskas; Kalindi Vaidya; Nicola G. Wallis; Scott B. Winram
ABSTRACT Bacterial enoyl-acyl carrier protein (ACP) reductase (FabI) catalyzes the final step in each elongation cycle of bacterial fatty acid biosynthesis and is an attractive target for the development of new antibacterial agents. High-throughput screening of the Staphylococcus aureus FabI enzyme identified a novel, weak inhibitor with no detectable antibacterial activity against S. aureus. Iterative medicinal chemistry and X-ray crystal structure-based design led to the identification of compound 4 [(E)-N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide], which is 350-fold more potent than the original lead compound obtained by high-throughput screening in the FabI inhibition assay. Compound 4 has exquisite antistaphylococci activity, achieving MICs at which 90% of isolates are inhibited more than 500 times lower than those of nine currently available antibiotics against a panel of multidrug-resistant strains of S. aureus and Staphylococcus epidermidis. Furthermore, compound 4 exhibits excellent in vivo efficacy in an S. aureus infection model in rats. Biochemical and genetic approaches have confirmed that the mode of antibacterial action of compound 4 and related compounds is via inhibition of FabI. Compound 4 also exhibits weak FabK inhibitory activity, which may explain its antibacterial activity against Streptococcus pneumoniae and Enterococcus faecalis, which depend on FabK and both FabK and FabI, respectively, for their enoyl-ACP reductase function. These results show that compound 4 is representative of a new, totally synthetic series of antibacterial agents that has the potential to provide novel alternatives for the treatment of S. aureus infections that are resistant to our present armory of antibiotics.
Antimicrobial Agents and Chemotherapy | 1997
Joseph W. Chow; Marcus J. Zervos; Stephen A. Lerner; Lee Ann Thal; Susan M. Donabedian; Deborah Dee Jaworski; Shane Tsai; Karen J. Shaw; Don B. Clewell
Journal of Bacteriology | 1995
Deborah Dee Jaworski; Don B. Clewell
Journal of Bacteriology | 1994
Deborah Dee Jaworski; Don B. Clewell
Plasmid | 1996
Deborah Dee Jaworski; Susan E. Flannagan; Don B. Clewell
Archive | 1998
Deborah Dee Jaworski; Karen Mary O'dwyer; Lisa Kathleen Shilling; Christopher Michael Traini; Min Wang; Edwina Imogen Wilding
Archive | 2001
Deborah Dee Jaworski; David J. Payne; Courtney Slater-Radosti; Kang Yan
Archive | 1998
Sanjoy Biswas; James R. Brown; Christine Marie Debouck; Deborah Dee Jaworski; Elizabeth Jane Lawlor; Jeffrey Mooney; Lisa K. Katz; Min Wang; Richard Warren; Magdalena Zalacain; Yi Yi Zhong
Archive | 2001
Min Wang; Judith M. Ward; Richard Lloyd Warren; Richard Oakley Nicholas; Leslie Marie Palmer; Julie M. Pratt; David Justin Charles Knowles; Michael Arthur Lonetto; Jeffrey Mooney; Michael Terence Black; Martin Karl Russell Burnham; Christine Debouck; Jason Craig Fedon; John Edward Hodgson; Deborah Dee Jaworski; Raymond Winfield Reichard; Martin Rosenberg; Christopher Michael Traini; Yi Yi Zhong