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Front Immunol ; 11: 1677, 2020.
Article in English | MEDLINE | ID: mdl-32973740

ABSTRACT

Tuberculosis (TB) is currently one of the leading causes of global mortality. Medical non-compliance due to the length of the treatment and antibiotic side effects has led to the emergence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (M. tb) that are difficult to treat. A current therapeutic strategy attempting to circumvent this issue aims to enhance drug delivery to reduce the duration of the antibiotic regimen or dosage of first-line antibiotics. One such agent that may help is cyclic peptide [R4W4], as it has been shown to have antibacterial properties (in combination with tetracycline) against methicillin-resistant Staphylococcus aureus (MRSA) in the past. The objective of this study is to test cyclic peptide [R4W4] both alone and in combination with current first-line antibiotics (either isoniazid or pyrazinamide) to study the effects of inhibition of M. tb inside in vitro human granulomas. Results from our studies indicate that [R4W4] is efficacious in controlling M. tb infection in the granulomas and has enhanced inhibitory effects in the presence of first-line antibiotics.


Subject(s)
Antibiotics, Antitubercular/pharmacology , Granuloma/drug therapy , Isoniazid/pharmacology , Mycobacterium tuberculosis/drug effects , Peptides, Cyclic/pharmacology , Pyrazinamide/pharmacology , Tuberculosis/drug therapy , Adolescent , Adult , Aged , Autophagy/drug effects , Cytokines/metabolism , Drug Therapy, Combination , Granuloma/metabolism , Granuloma/microbiology , Host-Pathogen Interactions , Humans , Microbial Viability/drug effects , Middle Aged , Mycobacterium tuberculosis/growth & development , Oxidative Stress , Tuberculosis/metabolism , Tuberculosis/microbiology , Young Adult
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