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Broad spectrum antibiotic activity of the arylomycin natural products is masked by natural target mutations

P.A. Smith, T.C. Roberts, F.E. Romesberg, Chem. Biol. (2010) 17:1223-1231.
pubpic2010smithWe demonstrates that the apparently narrow spectrum of the arylomycin natural products results not from intrinsic limitations, but from target mutations and that the arylomycins have a much broader spectrum of activity than previously thought.

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The psychotrimine natural products have antibacterial activity against Gram-positive bacteria and act via membrane disruption

M.A. Schallenberger, T. Newhouse, P.S. Baran, F.E. Romesberg, J. Antibiot. (2010) 63:685-687.
pubpic2010schallenbergerPlants provide a unique source of diverse secondary metabolites with potentially important biological activities, with one of the most promising classes being the indole alkaloids. One such indole alkaloid natural product is psychotrimine, which has attracted considerable interest from the synthetic and medicinal chemistry communities owing to its unusual connectivity between tryptamine subunits. Here, we examine the potential antibacterial activity of this unique indole alkaloid.

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Secretion of the chlamydial virulence factor CPAF requires Sec-dependent pathway

D. Chen, L. Lei, C. Lu, R. Flores, M.P. DeLisa, T.C. Roberts, F.E. Romesberg, G. Zhong, Microbiology (2010) 156:3031-3040.
pubpic2010chenCPAF is secreted into host cytosol to degrade various host factors for benefiting chlamydial intracellular survival. Here, we show experimental evidence that the chlamydial virulence factor CPAF relies on sec-dependent transport for crossing the chlamydial organism inner membrane.

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Solution structure, mechanism of replication, and optimization of an unnatural base pair

D.A. Malyshev, D.A. Pfaff, S.I. Ippoliti, G.T. Hwang, T.J. Dwyer, F.E. Romesberg, Chem. Eur. J. (2010) 16:12650-12659.
pubpic2010malyshevWe synthesize a variety of derivatized unnatural base pairs and characterize their structures and DNA polymerase-mediated replication. We also present further evidence supporting an intercalation-based mechanism of replication, and show that dDMO—d5SICS represents significant progresstoward the expansion of the genetic alphabet.

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Directed evolution of DNA polymerases for next generation sequencing

A.M. Leconte, M.P. Patel, L.E. Sass, P. McInerney, M. Jarosz, L. Kung, J.L. Bowers, P.R. Buzby, J.W. Efcavitch, F.E. Romesberg, Angew. Chem. Int. Ed. (2010) 34:5921-5924.
pubpic2010xxWe identified a mutant of Taq DNA polymerase that incorporates fluorophore-labeled substrates 50- to 400-fold more efficiently into scarred primers in solution and also demonstrates significantly improved performance under actual sequencing conditions.

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SOS regulatory elements are essential for UPEC pathogenesis

B. Li, P. Smith, D.J. Horvath, Jr, F.E. Romesberg, S.S. Justice, Microb. Infect. (2010) 12:662-668.
pubpic2010liEpithelial cells are highly regarded as the first line of defense against microorganisms, but the mechanisms used to control bacterial diseases are poorly understood. A component of the DNA damage repair regulon, SulA, is essential for UPEC virulence in a mouse model for human urinary tract infection, suggesting that DNA damage is a key mediator in the primary control of pathogens within the epithelium. In this study, we examine the role of DNA damage repair regulators in the intracellular lifestyle of UPEC within superficial bladder epithelial cells.