Beta-lactam combination treatment overcomes rifampicin resistance in Mycobacterium tuberculosis.

The significant global impact of tuberculosis (TB) on human health is exacerbated by the increasing prevalence of multi-drug resistant tuberculosis (MDR-TB) and the challenges of novel drug discovery for the treatment of drug-susceptible and drug-resistant strains of M. tuberculosis. Rifampicin is a key first-line TB drug and rifampicin resistance is a major obstacle to treating MDR-TB.

An LNP-mRNA vaccine modulates innate cell trafficking and promotes polyfunctional Th1 CD4 T cell responses to enhance BCG-induced protective immunity against Mycobacterium tuberculosis.

Background: Mycobacterium tuberculosis remains the largest infectious cause of mortality worldwide, even with over a century of widespread administration of the only licenced tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG). mRNA technology remains an underexplored approach for combating chronic bacterial infections such as TB.

Methods: We have developed a lipid nanoparticle (LNP)-mRNA vaccine, termed mRNA, encoding for the M.

Analogue of the natural product ecumicin causes sustained growth inhibition of Mycobacterium tuberculosis under multiple growth conditions.

Multi-drug-resistant Mycobacterium tuberculosis is an escalating global health problem, and a strong pipeline of novel compounds is needed to combat rising antimicrobial resistance. Ecumicin is a novel analogue of the natural antimycobacterial cyclic peptide ecumicin, with selective activity against Mycobacterium species. The activity of ecumicin∗ was compared to that of frontline tuberculosis therapies under in vitro conditions representative of niches where M.

Mn and Zn-Doped Multivariate Metal-Organic Framework as a Metalloimmunological Adjuvant to Promote Protection Against Tuberculosis Infection.

A first-in-class vaccine adjuvant delivery system, Mn-ZIF, is developed by incorporating manganese (Mn) into the zinc-containing zeolitic-imidazolate framework-8 (ZIF-8). The mixed metal approach, which allowed for tunable Mn doping, is made possible by including a mild reducing agent in the reaction mixture. This approach allows up to 50% Mn, with the remaining 50% Zn within the ZIF.

Lung IL-17A-Producing CD4 T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines.

Tuberculosis (TB), caused by , results in approximately 1.6 million deaths annually. BCG is the only TB vaccine currently in use and offers only variable protection; however, the development of more effective vaccines is hindered by a lack of defined correlates of protection (CoP) against .

Potent Bactericidal Antimycobacterials Targeting the Chaperone ClpC1 Based on the Depsipeptide Natural Products Ecumicin and Ohmyungsamycin A.

Ohmyungsamycin A and ecumicin are structurally related cyclic depsipeptide natural products that possess activity against (Mtb), the causative agent of tuberculosis (TB). Herein, we describe the design and synthesis of a library of analogues of these two natural products using an efficient solid-phase synthesis and late-stage macrolactamization strategy. Lead analogues possessed potent activity against Mtb in vitro (minimum inhibitory concentration 125-500 nM) and were shown to inhibit protein degradation by the mycobacterial ClpC1-ClpP1P2 protease with an associated enhancement of ClpC1 ATPase activity.