A. Craney, F.E. Romesberg, Bioorg. Med. Chem. (2016) 24:6225-6226.
We serve as guest editors for a special issue of Bioorg. Med. Chem. In this preface, we give a bit of background on drug discovery and the impending crisis posed by antibiotic resistance, as well as an overview of the contributed articles.
S.I. Walsh, A. Craney, F.E. Romesberg, Bioorg. Med. Chem. (2016) 24:6370-6378.
We review how the inhibition of SPase may affect bacterial virulence, and how SPase itself contributes to functions beyond mediating bacterial secretion.
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.
In 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..
M.A. Schallenberger, T. Newhouse, P.S. Baran, F.E. Romesberg, J. Antibiot. (2010) 63:685-687.
Plants 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.
R.T. Cirz and F.E. Romesberg, Crit. Rev. Biochem. Mol. Biol. (2007) 42:341-354.
We 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.
P.A. Smith and F.E. Romesberg, Nat. Chem. Biol. (2007) 3:549-556.
An 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.
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.
We 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]