Dirk Schnappinger

Analysis code for: Comprehensive mapping of essential-gene interactions in M. tuberculosis

Isaac J. Kresse, Natalie Y. Sayegh, Vanisha Munsamy-Govender, Allen Na et autres

Code and a runnable example dataset for the probabilistic genetic-interaction analysis in Kresse, Sayegh, et al., "Comprehensive mapping of essential-gene interactions in M. tuberculosis" (Nature, accepted). Includes the per-guide-pair two-line fitness model, the per-screen and joint Bayesian Normal/Uniform mixture models, and a …

us, ca (code pays fourni par la source)

Analysis code for: Comprehensive mapping of essential-gene interactions in M. tuberculosis

Isaac J. Kresse, Natalie Y. Sayegh, Vanisha Munsamy-Govender, Allen Na et autres

Code and a runnable example dataset for the probabilistic genetic-interaction analysis in Kresse, Sayegh, et al., "Comprehensive mapping of essential-gene interactions in M. tuberculosis" (Nature, accepted). Includes the per-guide-pair two-line fitness model, the per-screen and joint Bayesian Normal/Uniform mixture models, and a …

us, ca (code pays fourni par la source)

The Natural Product Corramycin Acts as a DNA Gyrase Poison and Overcomes Fluoroquinolone Resistance in Mycobacterium tuberculosis

Franziska Fries, Jennifer E. Herrmann, Michael Dal Molin, Yaëlle Wormser et autres

Despite significant advancements in drug development and discovery, tuberculosis remains one of the world's deadliest infectious diseases. The rise and global spread of multidrug-resistant strains underscore a critical need for new antibiotics with distinct mechanisms of action. Screening of a myxobacterial extract …

de, fr, us (code pays fourni par la source)

Erratum for Theriault et al., “Utilization of a CRISPRi-based ex vivo challenge model to reveal temporally dependent gene essentiality in intracellular Mycobacterium tuberculosis ”

Monique E. Theriault, Andrew I. Wong, Michael A. DeJesus, Davide Pisu et autres

Identification and Evaluation of Dibasic Piperidines as Cell Wall Inhibitors against Mycobacterium tuberculosis

Claire Naylor, Gareth Prosser, Tracy Bayliss, Lila F. Berle et autres

remains a significant burden. Although effective treatment regimens exist, drug resistance has continued to emerge. This clinical resistance, combined with side effects and protracted treatment times from the current front-line therapies, means that there is a need to identify novel agents to …

gb, no, us, es (code pays fourni par la source)

Design, Synthesis and Biological Evaluation of Potent Piperazine-Based BioA Inhibitors Targeting Biotin Biosynthesis in Mycobacterium tuberculosis

Qiang Liu, Curtis A. Engelhart, Joshua B. Wallach, Peng Ge et autres

We recently reported C48, a potent and orally effective inhibitor targeting biotin biosynthesis in Mycobacterium tuberculosis ( Mtb ). Notably, C48 exhibited a favorable pharmacokinetic profile and suppressed Mtb growth in a mouse model that recapitulates human biotin physiology, demonstrating that biotin …

us (code pays fourni par la source)

Utilization of a CRISPRi-based ex vivo challenge model to reveal temporally dependent gene essentiality in intracellular Mycobacterium tuberculosis

Monique E. Theriault, Andrew I. Wong, Michael A. DeJesus, Davide Pisu et autres

ABSTRACT Mycobacterium tuberculosis (Mtb) remains a leading cause of infectious disease mortality worldwide, largely due to its ability to survive within host macrophages. Despite advances in understanding the environmental pressures Mtb encounters in vivo , the genetic requirements for adaptation and survival …

us (code pays fourni par la source)

Mycobacterium tuberculosis long-chain fatty acid resistome reveals universal stress protein TB15.3 as essential for infection

Alexandre Jorge Pinto, Marco da Silva, Joana A. Santos, Brian C. VanderVen et autres

The human pathogen Mycobacterium tuberculosis (Mtb) thrives in lipid-rich microenvironments. A strong body of evidence demonstrated that, during infection, Mtb utilizes long-chain fatty acids (LCFA) as a preferred carbon source. However, LCFA also have antimicrobial properties. Mtb must therefore employ mechanisms to …

pt, us (code pays fourni par la source)

Structure−Activity relationship and optimization of drug-like properties of antituberculosis 3-(4,4-dimethyl-1,4-azasilinane)methylpyrazole MmpL3 inhibitors

Lutete Peguy Khonde, Nashied Peton, Keabetswe Masike, Tania Valentine et autres

Structure-activity relationship studies of previously reported 3-(4,4-dimethyl-1,4-azasilinane) methylpyrazoles with potent anti-tuberculosis activity were conducted to identify leads with drug-like properties by optimizing the lipophilicity of the compounds. Removal of phenyl substituents at 1 or 5 positions of the pyrazole ring or introducing …

Afrique du Sud, it, us (code pays fourni par la source)

Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation

Dirk Schnappinger, Steven J. Berthel, Helena I. Boshoff, Inna V. Krieger et autres

Despite the approval of two first-in-class anti-tuberculars over the past two decades, the global burden of tuberculosis (TB) remains unacceptably high, in part due to the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). This review summarizes advances and ongoing …

us, de, gb, Afrique du Sud (code pays fourni par la source)

A periplasmic protein complex mediates arabinofuranosyltransferase activity and intrinsic drug resistance in Mycobacterium tuberculosis

Thaís Klevorn, Christopher D. Brown, Christine D. Hardy, Bonnie J. Cuthbert et autres

(Mtb) is a major barrier to effective tuberculosis (TB) treatment and is largely due to its complex, impermeable cell envelope. We identified a periplasmic protein complex comprising FecB and Rv3035 that is essential for maintaining envelope integrity and mediating intrinsic multidrug resistance …

us (code pays fourni par la source)

Activation of l-histidine biosynthesis as a new antibiotic strategy against Mycobacterium tuberculosis

Debbie M. Hunt, João Pedro Pisco, Angela Rodgers, Cesira de Chiara et autres

The increasing prevalence of antimicrobial resistance is an important challenge that warrants new approaches to antibiotic development. Currently, all antibiotics inhibit biological processes. To explore whether activation of a biochemical pathway can elicit bactericidal effects we engineered variants of Mycobacterium tuberculosis ATP-phosphoribosyltransferase …

gb, us (code pays fourni par la source)