Unraveling the mechanisms of intrinsic drug resistance in Mycobacterium tuberculosis

NC Poulton, JM Rock - Frontiers in cellular and infection microbiology, 2022 - frontiersin.org
Tuberculosis (TB) is among the most difficult infections to treat, requiring several months of
multidrug therapy to produce a durable cure. The reasons necessitating long treatment times …

Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis

B Bosch, MA DeJesus, NC Poulton, W Zhang… - Cell, 2021 - cell.com
Antibacterial agents target the products of essential genes but rarely achieve complete
target inhibition. Thus, the all-or-none definition of essentiality afforded by traditional genetic …

Gradients in gene essentiality reshape antibacterial research

AM Hogan, ST Cardona - FEMS Microbiology Reviews, 2022 - academic.oup.com
Essential genes encode the processes that are necessary for life. Until recently, commonly
applied binary classifications left no space between essential and non-essential genes. In …

Essential gene knockdowns reveal genetic vulnerabilities and antibiotic sensitivities in Acinetobacter baumannii

RD Ward, JS Tran, AB Banta, EE Bacon, WE Rose… - Mbio, 2024 - Am Soc Microbiol
The emergence of multidrug-resistant Gram-negative bacteria underscores the need to
define genetic vulnerabilities that can be therapeutically exploited. The Gram-negative …

Morphological and transcriptional responses to CRISPRi knockdown of essential genes in Escherichia coli

MR Silvis, M Rajendram, H Shi, H Osadnik, AN Gray… - MBio, 2021 - Am Soc Microbiol
ABSTRACT CRISPR interference (CRISPRi) has facilitated the study of essential genes in
diverse organisms using both high-throughput and targeted approaches. Despite the …

ORBIT for E. coli: kilobase-scale oligonucleotide recombineering at high throughput and high efficiency

SH Saunders, AM Ahmed - Nucleic Acids Research, 2024 - academic.oup.com
Microbiology and synthetic biology depend on reverse genetic approaches to manipulate
bacterial genomes; however, existing methods require molecular biology to generate …

Guide RNA structure design enables combinatorial CRISPRa programs for biosynthetic profiling

J Fontana, D Sparkman-Yager, I Faulkner… - Nature …, 2024 - nature.com
Engineering metabolism to efficiently produce chemicals from multi-step pathways requires
optimizing multi-gene expression programs to achieve enzyme balance. CRISPR-Cas …

CRISPRi functional genomics in bacteria and its application to medical and industrial research

AL Enright, WJ Heelan, RD Ward… - … and Molecular Biology …, 2024 - Am Soc Microbiol
Functional genomics is the use of systematic gene perturbation approaches to determine the
contributions of genes under conditions of interest. Although functional genomic strategies …

Weak links: Advancing target‐based drug discovery by identifying the most vulnerable targets

B Bosch, MA DeJesus… - Annals of the New …, 2024 - Wiley Online Library
Mycobacterium tuberculosis remains the most common infectious killer worldwide despite
decades of antitubercular drug development. Effectively controlling the tuberculosis (TB) …

Spurious regulatory connections dictate the expression‐fitness landscape of translation factors

JB Lalanne, DJ Parker, GW Li - Molecular Systems Biology, 2021 - embopress.org
During steady‐state cell growth, individual enzymatic fluxes can be directly inferred from
growth rate by mass conservation, but the inverse problem remains unsolved. Perturbing the …