AUTHOR=Hernandez Joshua , Ashley David , Cao Ruoqiong , Abrahem Rachel , Nguyen Timothy , To Kimberly , Yegiazaryan Aram , Akinwale David Ajayi , Kumar Tiwari Rakesh , Venketaraman Vishwanath 

TITLE=Cyclic Peptide [R4W4] in Improving the Ability of First-Line Antibiotics to Inhibit Mycobacterium tuberculosis Inside in vitro Human Granulomas

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01677

DOI=10.3389/fimmu.2020.01677

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Mycobacterium tuberculosis</italic> (<italic>M. tb</italic>) 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 [R<sub>4</sub>W<sub>4</sub>], as it has been shown to have antibacterial properties (in combination with tetracycline) against methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA) in the past. The objective of this study is to test cyclic peptide [R<sub>4</sub>W<sub>4</sub>] both alone and in combination with current first-line antibiotics (either isoniazid or pyrazinamide) to study the effects of inhibition of <italic>M. tb</italic> inside <italic>in vitro</italic> human granulomas. Results from our studies indicate that [R<sub>4</sub>W<sub>4</sub>] is efficacious in controlling <italic>M. tb</italic> infection in the granulomas and has enhanced inhibitory effects in the presence of first-line antibiotics.</p>