News

TB R&D Update: Semisynthetic antibiotic effective against sensitive and drug resistant tuberculosis in vitro

Richard E. Lee et al. Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux. Nature Medicine. 2014. March 6; 20(152). doi:10.1038/nm.3458

Abstract:

Although the classical antibiotic spectinomycin is a potent bacterial protein synthesis inhibitor, poor antimycobacterial activity limits its clinical application for treating tuberculosis. Using structure-based design, we generated a new semisynthetic series of spectinomycin analogs with selective ribosomal inhibition and excellent narrow-spectrum antitubercular activity. In multiple murine infection models, these spectinamides were well tolerated, significantly reduced lung mycobacterial burden and increased survival. In vitro studies demonstrated a lack of cross resistance with existing tuberculosis therapeutics, activity against multidrug-resistant (MDR) and extensively drug-resistant tuberculosis and an excellent pharmacological profile. Key to their potent antitubercular properties was their structural modification to evade the Rv1258c efflux pump, which is upregulated in MDR strains and is implicated in macrophage-induced drug tolerance. The antitubercular efficacy of spectinamides demonstrates that synthetic modifications to classical antibiotics can overcome the challenge of intrinsic efflux pump-mediated resistance and expands opportunities for target-based tuberculosis drug discovery.

Additional Coverage:

New antibiotic could overcome drug-resistant TB

Treating tuberculosis with spectinamides

Spectinamides: New class of mutant drugs makes progress against TB

Drug-resistant tuberculosis: a new shot on goal

New hope against tuberculosis: spectinamides

Additional TB R&D Updates:

Antibody-Free Detection of Mycobacterium tuberculosis Antigen Using Customized Nanotraps

Treating Tuberculosis and AIDS Together Saves Lives

Acetic Acid, the Active Component of Vinegar, Is an Effective Tuberculocidal Disinfectant

CAfGEN receives $3 million grant to study progression of TB and HIV

Chemist gets US patent for solution to resistance problem

More News
23 Aug 2022
The PAN-TB collaboration announced initial plans for a Phase 2 clinical trial evaluating two novel drug regimens to treat Tuberculosis. Sponsored by the Bill and Melinda Gates Foundation, the PAN-TB, or “Project to Accelerate New Treatments for Tuberculosis”, collaboration brings together non-...
4 May 2022
Earlier this week, the World Health Organization (WHO) released a rapid communication which detailed the upcoming changes to the treatment guidance for drug-resistant tuberculosis (DR-TB). These guidelines are used to inform national TB programmes globally on how to treat patients with these...
5 Apr 2022
On April 01, 2022, the Stop TB Partnership launched the second online consultation for the new Global Plan to End TB 2023-2030. Over the years, the Global Plans have been important tools for advocacy and resource mobilization, and served as a reference document for donors and stakeholders. In May...