In This Issue Cite This: ACS Chem. Biol. 2018, 13, 3220−3220
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CROSS-LINKING COLIBACTINS
target the dyes to fungal cells, the authors attached fluorescent dyes to the antifungal drug fluconazole. By varying the dye, the authors can tune the localization of the tracker to different organelles in live cells. They ultimately were able to identify a derivative that localizes to the endoplasmic reticulum of Candida cells, without antifungal activity.
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Colibactins are secondary metabolites produced in several strains of Enterobacteriaceae as part of the nonribosomal peptide synthetase−polyketide synthase biosynthetic pathway. Colibactins are genotoxic and associated with gastrointestinal dysfunction and colorectal cancer. These metabolites are difficult to characterize, however, as none have been isolated from any producing microbes. However, the effects of colibactins may be studied by proxy, using synthetic derivatives that produce similar genotoxic effects, such as DNA doublestrand breaks (DSBs) in vitro. In this issue, Shine and co-workers (DOI: 10.1021/ acschembio.8b00714) evaluate model colibactins to elucidate the molecular mechanisms of genotoxicity in infected cells. In particular, they measure the degree of DNA damage induced by synthetic colibactins via quantification of the damage marker phospho-SER139-histone H2AX (H2AX). Additionally, the authors explore the cellular transport mechanisms of model colibactins.
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pubs.acs.org/acschemicalbiology
RIP, PATHOGENS
There is a growing and urgent need to discover novel antibiotic compounds. One major hurdle in this endeavor is determining their mechanism of action. Bacterial cytological profiling is an efficient method for elucidating the biosynthetic pathway targeted by the antibiotic. However, some compounds appear to inhibit more than one cellular pathway, making them difficult to study. Here, Peters and co-workers (DOI: 10.1021/acschembio.8b00273) employ a new technique called rapid inducible profiling (RIP), which profiles the effects of rapid protein degradation on bacterial cytological profiles. In this way, profiles for new antibiotic targets can be identified. The authors use RIP to profile the cytological fingerprint of the pyrimidine nucleotide biosynthetic pathway. Most enzymes in this pathway were conserved, thus representing potential new targets for antibiotic drug development.
PEEKING INTO FUNGAL CELLS
Organelle-specific fluorescent dyes are an invaluable tool in chemical biology for tracking cellular function and the various types of interactions that occur between organelles. While most commercially available dyes are well suited for labeling in human or plant cells, they are less optimized for the structural and functional intricacies of fungal cells, which can provide insights into mechanisms of infection. Now, Benhamou et al. (DOI: 10.1021/acschembio.8b00782) report on new small molecules that selectively label the organelles of pathogenic Candida yeast cells. To © 2018 American Chemical Society
Published: December 21, 2018 3220
DOI: 10.1021/acschembio.8b01061 ACS Chem. Biol. 2018, 13, 3220−3220
