Tuberculosis still kills a lot of people worldwide (1.6 million deaths per year). Previous findings demonstrated that induced myeloid leukemia cell differentiation protein Mcl-1 inhibitors reduced the growth of Mycobacterium tuberculosis in human macrophages, but when inhibiting multiple proteins from the Mcl-1/Bcl-2 family, the result was more effective and in a more complex human in vitro granuloma environment.
Researchers from Michigan State University and Tarn Biosciences Inc. have published their work on the discovery and preclinical evaluation of novel antimycobacterial nitro-containing compounds.
One way to prevent the effect of a molecule is to use the cell’s own machinery to break it down. This is what the PROTAC technology does, an acronym for proteolysis targeting chimera, or BacPROTAC, when applied to bacteria. A study led by Austrian and German scientists has demonstrated the effectiveness of this technique in eliminating the tuberculosis pathogen Mycobacterium tuberculosis (Mtb). The finding opens the door to the BacPROTAC strategy as an alternative to the development of drugs against this microorganism.
Prior to the COVID-19 pandemic, tuberculosis ranked as the leading cause of infectious disease deaths worldwide; the increase of multidrug-resistant Mycobacterium tuberculosis puts some pressure on the search for new tuberculosis therapeutic approaches. Researchers from Sanofi SA and their collaborators have published preclinical results on a sequanamycin – sequanamycin 9 (SEQ-9) – for the potential treatment of tuberculosis.
Researchers at the University of Cape Town have compared the T-cell responses of individuals who were infected with Mycobacterium tuberculosis but were able to control the infection to those who developed active disease. The researchers wrote that the shared antigens in controllers “can be considered as high-priority targets for future vaccine development.” Their results were published online in Nature Medicine on Jan. 5, 2023. In their experiments, the team first sequenced the CDR3β region of the T-cell repertoire in a total of 166 individuals with M. tuberculosis infection who progressed to either TB or controlled infection.
GSK plc scientists seeking compounds with the potential to treat resistant tuberculosis infection identified a series of tetrazole agents using phenotypic screening against Mycobacterium tuberculosis.
Scientists have discovered a new antibiotic called evybactin that is able to selectively target Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB) lung infections. As described in NatureChemicalBiology on Aug. 22, 2022. the work is still at an early stage and requires further validation. But, if successful in clinical trials, evybactin could form part of a new group of specific antibiotics designed to target TB.
The largest ever global study of tuberculosis has identified all the mutations conferring resistance to approved antimicrobials, setting the scene for more rational use of drugs, increasing mechanistic understanding of how Mycobacteriumtuberculosis develops resistance to antibiotics and pointing to new drug targets.
Researchers from the State University of New York at Albany have identified small molecules that could inhibit intein self-splicing from the protein PrP8 in the fungal pathogens Cryptococcus neoformans and Cryptococcus gattii, emerging pathogens that can cause fungal meningitis in immunocompromised patients.
