1,720,984 research outputs found
Using a Fragment-based approach to identify new hits to drugs against Mycobacterium tuberculosis Pantothenate Kinase.
No full textImprove protection to prevent infections: application of reverse vaccinology against cystic fibrosis pathogens.
No full textReverse vaccinology is a powerful tool that was recently used to develop vaccines starting from a pathogen genome. Some bacterial infections have the necessity to be prevented then treated. For example, individuals with chronic pulmonary diseases, such as Cystic Fibrosis, are prone to develop infections and biofilms in the thick mucus that covers their lungs, mainly caused by Burkholderia cepacia complex, Haemophilus influenzae, Mycobacterium abscessus complex, Pseudomonas aeruginosa and Staphylococcus aureus. These infections are complicated to treat and prevention remains the best strategy. Despite the availability of vaccines against some strains of those pathogens, it is necessary to improve the immunization of people with Cystic Fibrosis against all of them. An effective approach is to develop a broad-spectrum vaccine to utilize proteins that are well conserved across different species. In this context, reverse vaccinology, a method based on computational analysis of the genome of various microorganisms, appears as one of the most promising tools for the identification of putative targets for broad-spectrum vaccine development. This review provides an overview of the vaccines that are under development by reverse vaccinology against the aforementioned pathogens, as well as the progress made so far
Nitric oxide-releasing compounds for the treatment of lung infections
No full textThe spread of acquired drug resistance and of microorganisms naturally resistant to antibiotics is a major threat to global health, leading to an urgent need for novel antimicrobial compounds. Exogenous nitric oxide (NO) represents an attractive and promising antimicrobial approach, showing both bactericidal and biofilm dispersal activities. Numerous studies have been performed to develop NO donor scaffolds, including small molecules, macromolecular compounds, nanoparticles (NPs), and polymeric materials. This approach has resulted in successful outcomes, with some NO-releasing compounds entering clinical practice. In this review, we highlight the importance of this strategy, with a focus on lung infections
Structural insights for the development of novel antituberculars targeting the iron uptake pathway.
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A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis MbtI and MPtpB
No full textMycobacterium abscessus, an Emerging and Worrisome Pathogen among Cystic Fibrosis Patients.
No full textNontuberculous mycobacteria (NTM) have recently emerged as important pathogens among cystic fibrosis (CF) patients worldwide. Mycobacterium abscessus is becoming the most worrisome NTM in this cohort of patients and recent findings clarified why this pathogen is so prone to this disease. M. abscessus drug therapy takes up to 2 years and its failure causes an accelerated lung function decline. The M. abscessus colonization of lung alveoli begins with smooth strains producing glycopeptidolipids and biofilm, whilst in the invasive infection, "rough" mutants are responsible for the production of trehalose dimycolate, and consequently, cording formation. Human-to-human M. abscessus transmission was demonstrated among geographically separated CF patients by whole-genome sequencing of clinical isolates worldwide. Using a M. abscessus infected CF zebrafish model, it was demonstrated that CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction seems to have a specific role in the immune control of M. abscessus infections only. This pathogen is also intrinsically resistant to many drugs, thanks to its physiology and to the acquisition of new mechanisms of drug resistance. Few new compounds or drug formulations active against M. abscessus are present in preclinical and clinical development, but recently alternative strategies have been investigated, such as phage therapy and the use of β-lactamase inhibitors
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