Frontiers in Immunology (Aug 2020)

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

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

DOI
https://doi.org/10.3389/fimmu.2020.01677
Journal volume & issue
Vol. 11

Abstract

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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.

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