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Axinellamines as broad-spectrum antibacterial agents: scalable synthesis and biology

R.A. Rodriguez, D.B. Steed, Y. Kawamata, S. Su, P.A. Smith, T.C. Steed, F.E. Romesberg, P.S. Baran, J. Am. Chem. Soc. (2014) 136:15403-15413.
pubpic2014rodriguezIn this collaborative work with the Baran Lab, we show that the axinellamines have promising activity against Gram-positive and Gram-negative bacteria, suggesting that their scaffold has the potential for further development. Details regarding their mode of action remain to be elucidated, but the axinellamines appear to cause secondary membrane destabilization and may inhibit normal septum formation..

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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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Controlling mutation: intervening in evolution as a therapeutic strategy

R.T. Cirz and F.E. Romesberg, Crit. Rev. Biochem. Mol. Biol. (2007) 42:341-354.
pubpic2007cirzWe review what is known about induced mutagenesis in bacteria as well as evidence that it contributes to the evolution of antibiotic resistance and we discuss the possibility that components of induced mutation pathways might be targeted for inhibition as a novel therapeutic strategy to prevent the evolution of antibiotic resistance.

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Combating bacteria and drug-resistance by inhibiting mechanisms of persistence and adaptation

P.A. Smith and F.E. Romesberg, Nat. Chem. Biol. (2007) 3:549-556.
pubpic2007smithAn improved understanding of bacterial stress responses and evolution suggests that in the ability of bacteria to survive antibiotic therapy either by transiently tolerating antibiotics or by evolving resistance may require specific biochemical processes. We review early efforts toward inhibiting these processes as a means to prolong the efficacy of current antibiotics and provide an alternative to escalating the current arms race between antibiotics and bacterial resistance.

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The complete and SOS-mediated response of Staphylococcus aureus to the antibiotic ciprofloxacin

R.T. Cirz, M.B. Jones, N.A. Gingles, T.D. Minogue, B. Jarrahi, S.N. Peterson, F.E. Romesberg, J. Bacteriol. (2007) 189:531-539.
pubpic2006dcirzWe characterize the global transcriptional response of S. aureus to ciprofloxacin and find that the drug induces prophage mobilization as well as significant alterations in metabolism, most notably the up-regulation of the tricarboxylic acid cycle.[Download Supporting Information]