A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against .

The efficacy of many compounds against is often limited when administered via conventional oral or injection routes due to suboptimal pharmacokinetic characteristics. Inhalation-based delivery methods have been investigated to achieve high local therapeutic doses in the lungs. However, previous models, typically employing wild-type strains, were intricate, time-consuming, labor-intensive, and with poor reproducibility.

MtrAB two-component system is crucial for the intrinsic resistance and virulence of Mycobacterium abscessus.

Mycobacterium abscessus (Mab) poses serious therapeutic challenges, largely due to its intrinsic resistance to many antibiotics. The development of targeted therapeutic strategies necessitates the identification of bacterial factors that contribute to its reduced susceptibility to antibiotics and/or to the killing by its host cells. In this study, we discovered that Mab strains with disrupted mtrA, mtrB or both, or a gene-edited mtrA encoding MtrA with Tyr102Cys mutation, exhibited highly increased sensitivity to various drugs compared to the wild-type Mab.

The gene is responsible for intrinsic resistance to various drugs and virulence in by regulating cell division.

exhibits intrinsic resistance to most antibiotics, hence leading to infections that are difficult to treat. To address this issue, the identification of new molecular targets is essential for the development or repositioning of therapeutic agents. This study demonstrated that the -knockout strain, Mab, became significantly susceptible to a range of antibiotics, not only but also exhibited susceptibility to rifabutin, bedaquiline, and linezolid .

EmbB and EmbC regulate the sensitivity of to echinomycin.

Treatment of (Mab) infections is very challenging due to its intrinsic resistance to most available drugs. Therefore, it is crucial to discover novel anti-Mab drugs. In this study, we explored an intrinsic resistance mechanism through which Mab resists echinomycin (ECH).

Bactericidal and sterilizing activity of sudapyridine-clofazimine-TB47 combined with linezolid or pyrazinamide in a murine model of tuberculosis.

As an obligate aerobe, relies on its branched electron transport chain (ETC) for energy production through oxidative phosphorylation. Regimens targeting ETC exhibit promising potential to enhance bactericidal activity against and hold the prospect of shortening treatment duration. Our previous research demonstrated that the bacteriostatic drug candidate TB47 (T) inhibited the growth of by targeting the cytochrome complex and exhibited synergistic activity with clofazimine (C).

Indole Propionic Acid Disturbs the Normal Function of Tryptophanyl-tRNA Synthetase in .

Tuberculosis (TB) is the leading infectious disease caused by and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against and .

Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Clinical Isolates Collected in Guangzhou Chest Hospital, China.

Objective: Rifampicin (RIF)-resistance, a surrogate marker for multidrug-resistant tuberculosis (TB), is mediated by mutations in the gene. We aimed to investigate the prevalence of mutations pattern in the entire gene of clinical isolates and their association with resistance level to RIF.

Methods: Among 465 clinical isolates collected from the Guangzhou Chest Hospital, drug-susceptibility of 175 confirmed strains was performed via the proportion method and Bactec MGIT 960 system.