The Effects of Cyclic Peptide [R4W4] in Combination with First-line Therapy on the Survival of Mycobacterium avium

Authors

Melissa Kelley, Western University of Health Sciences
Kayvan Sasaninia, Western University of Health Sciences
Ali Badaoui, Western University of Health Sciences
Ira Glassman, Western University of Health Sciences
Arbi Abnousian, Western University of Health Sciences
Nadia Rai, Chapman University
Rakesh K. Tiwari, Western University of Health Sciences
Vishwanath Venketaraman, Western University of Health Sciences

Document Type

Article

Publication Date

4-15-2025

Abstract

Background: Mycobacterium avium (M. avium) is a nontuberculous mycobacterium (NTM) that can cause pulmonary and extrapulmonary infections mostly in immunocompromised individuals, such as those with HIV and diabetes. Traditionally, rifampicin (RIF) and azithromycin (AZ) have been used for a 12-month duration as first-line antibiotics against M. avium. Due to the increased multidrug resistance, novel ways, such as enhancement of macrophages response, are needed to provide adequate immune response required to clear M. avium infection.

Methods and findings: In this study, we aim to study the effects of using THP-1 cells, which are monocyte-like cells, to induce a macrophage response and control M. avium infection when used in combination with traditional treatments such as RIF and AZ in free and liposomal forms. Traditional treatments’ effects are studied when used alone and in combination therapy with cyclic peptide [R4W4] (liposomal encapsulated and liposomal combination). Colony-forming units (CFU) counts were assessed for all samples 3 hours, 4 days, and 8 days post-treatment. A significant reduction in the intracellular viability of M. avium was observed when THP-1 cells were treated with liposomal combination [R4W4]+RIF and liposomal combination [R4W4]+AZ compared to when treated with liposomal RIF or liposomal AZ alone, respectively.

Conclusion: Our findings show that liposomal combination [R4W4] is a promising adjuvant therapy to increase M. avium susceptibility to known antibiotics.

Comments

This article was originally published in Frontiers in Cellular and Infection Microbiology, volume 15, in 2025. https://doi.org/10.3389/fcimb.2025.1547376

Recommended Citation

Kelley M, Sasaninia K, Badaoui A, Glassman I, Abnousian A, Rai N, Tiwari RK and Venketaraman V (2025) The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium avium. Front. Cell. Infect. Microbiol. 15:1547376. https://doi.org/10.3389/fcimb.2025.1547376

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