Publications by authors named "M DeJesus"
Article Synopsis
- CRISPR interference (CRISPRi) is used to identify chemical-genetic interactions (CGIs) by determining how genes react to antibiotic exposure, helping discover potential drug targets and resistance mechanisms.
- The efficiency of different sgRNAs influences the growth rate of CRISPRi mutants, but optimal sgRNA for detecting drug interactions doesn't always correspond to the most efficient one. There exists a non-linear relationship between sgRNA strength and drug sensitivity.
- The CRISPRi-DR statistical method improves analysis by integrating sgRNA efficiencies with drug concentrations, showing better precision on complex datasets relative to other methods while effectively identifying gene interactions in microorganisms like Mycobacterium tuberculosis and E. coli.
Mycobacterium tuberculosis remains the most common infectious killer worldwide despite decades of antitubercular drug development. Effectively controlling the tuberculosis (TB) pandemic will require innovation in drug discovery. In this review, we provide a brief overview of the two main approaches to discovering new TB drugs-phenotypic screens and target-based drug discovery-and outline some of the limitations of each method.
View Article and Find Full Text PDFDrug-resistant bacteria are emerging as a global threat, despite frequently being less fit than their drug-susceptible ancestors. Here we sought to define the mechanisms that drive or buffer the fitness cost of rifampicin resistance (RifR) in the bacterial pathogen Mycobacterium tuberculosis (Mtb). Rifampicin inhibits RNA polymerase (RNAP) and is a cornerstone of modern short-course tuberculosis therapy.
View Article and Find Full Text PDFPathogenic mycobacteria are a significant cause of morbidity and mortality worldwide. The conserved whiB7 stress response reduces the effectiveness of antibiotic therapy by activating several intrinsic antibiotic resistance mechanisms. Despite our comprehensive biochemical understanding of WhiB7, the complex set of signals that induce whiB7 expression remain less clear.
View Article and Find Full Text PDFArticle Synopsis
- * Different sgRNAs can deplete target proteins to varying extents, influencing cellular growth and drug response; however, the most efficient sgRNAs aren't always the best for detecting drug synergies.
- * The new CRISPRi-DR statistical method combines sgRNA efficiencies with drug concentrations in a modified dose-response model to improve the identification of gene-drug interactions, outperforming some existing methods in terms of precision.