Kenneth Rachwalski

A ubiquitous Streptomyces biosynthetic megacluster encodes an arsenal of synergistic biotin-targeting antibiotics

Rodion Gordzevich, Min Xu, Wenliang Wang, Michael A. Cook et autres

Abstract The rise of multidrug-resistant pathogens underscores the urgent need for antibiotics that act through new targets and mechanisms. Biotin metabolism, essential in most bacteria, remains underexploited therapeutically. Here, we uncover a highly conserved, co-located biosynthetic megacluster in Streptomyces , a striking …

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Identifying Modulators of the Post-Antibiotic Effect

Alexa L. Gilberti, Megan M. Tu, Kenneth Rachwalski, Madeeha Ali et autres

The postantibiotic effect (PAE) is the delay in bacterial regrowth following antibiotic removal. It has important implications for dosing regimens since drugs that have extended activity following their elimination can be dosed less frequently, widening the therapeutic window. While the PAE has …

us, ca (code pays fourni par la source)

Identifying Modulators of the Post-Antibiotic Effect

Alexa L. Gilberti, Megan M. Tu, Kenneth Rachwalski, Muhammad Zeshan Ali et autres

ABSTRACT The post-antibiotic effect (PAE) is the delay in bacterial regrowth following antibiotic removal. It has important implications for dosing regimens since drugs that have extended activity following their elimination can be dosed less frequently, widening the therapeutic window. While the PAE …

us, ca (code pays fourni par la source)

Exploiting the fitness cost of metallo-β-lactamase expression can overcome antibiotic resistance in bacterial pathogens

Megan M. Tu, Lindsey A. Carfrae, Kenneth Rachwalski, Shawn French et autres

ca (code pays fourni par la source)

A screen for cell envelope stress uncovers an inhibitor of prolipoprotein diacylglyceryl transferase, Lgt, in Escherichia coli

Kenneth Rachwalski, Sean J. Madden, Nicole Ritchie, Shawn French et autres

The increasing prevalence of antibiotic resistance demands the discovery of antibacterial chemical scaffolds with unique mechanisms of action. Phenotypic screening approaches, such as the use of reporters for bacterial cell stress, offer promise to identify compounds while providing strong hypotheses for follow-on …

ca (code pays fourni par la source)

A platform for predicting mechanism of action based on bacterial transcriptional responses identifies an unusual DNA gyrase inhibitor

Shawn French, Amelia Bing Ya Guo, Michael J. Ellis, Julia P. Deisinger et autres

In the search for much-needed new antibacterial chemical matter, a myriad of compounds have been reported in academic and pharmaceutical screening endeavors. Only a small fraction of these, however, are characterized with respect to mechanism of action (MOA). Here, we describe a …

ca (code pays fourni par la source)

The inactivation of tolC sensitizes Escherichia coli to perturbations in lipopolysaccharide transport

Shawna Zhu, Mary Kate Alexander, Telmo O. Paiva, Kenneth Rachwalski et autres

The Escherichia coli outer membrane channel TolC complexes with several inner membrane efflux pumps to export compounds across the cell envelope. All components of these complexes are essential for robust efflux activity, yet E. coli is more sensitive to antimicrobial compounds when …

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A mobile CRISPRi collection enables genetic interaction studies for the essential genes of Escherichia coli

Kenneth Rachwalski, Megan M. Tu, Sean J. Madden, Shawn French et autres

Advances in gene editing, in particular CRISPR interference (CRISPRi), have enabled depletion of essential cellular machinery to study the downstream effects on bacterial physiology. Here, we describe the construction of an ordered E. coli CRISPRi collection, designed to knock down the expression …

ca (code pays fourni par la source)

A Screen for Cell Envelope Stress Uncovers a Novel Small Molecule Inhibitor of Prolipoprotein Diacylglyceryl Transferase, Lgt, in Escherichia coli

Kenneth Rachwalski, Sean J. Madden, Nicole Ritchie, Shawn French et autres

ca (code pays fourni par la source)

The fitness cost of metallo-β-lactamase expression is a potential target for new therapeutic approaches to carbapenem resistance

Megan M. Tu, Lindsey A. Carfrae, Kenneth Rachwalski, Shawn French et autres

ca (code pays fourni par la source)

A mobile CRISPRi collection enables genetic interaction studies for the essential genes of Escherichia coli

Kenneth Rachwalski, Megan M. Tu, Sean Madden, Shawn French et autres

ca (code pays fourni par la source)

A mobile CRISPRi collection enables genetic interaction studies for the essential genes of Escherichia coli

Kenneth Rachwalski, Megan M. Tu, Sean Madden, Shawn French et autres

ca (code pays fourni par la source)