The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium avium

BackgroundMycobacterium 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 du...

Full description

Saved in:
Bibliographic Details
Main Authors: Melissa Kelley, Kayvan Sasaninia, Ali Badaoui, Ira Glassman, Arbi Abnousian, Nadia Rai, Rakesh K. Tiwari, Vishwanath Venketaraman
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1547376/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850150884386799616
author Melissa Kelley
Kayvan Sasaninia
Ali Badaoui
Ira Glassman
Arbi Abnousian
Nadia Rai
Nadia Rai
Rakesh K. Tiwari
Rakesh K. Tiwari
Vishwanath Venketaraman
author_facet Melissa Kelley
Kayvan Sasaninia
Ali Badaoui
Ira Glassman
Arbi Abnousian
Nadia Rai
Nadia Rai
Rakesh K. Tiwari
Rakesh K. Tiwari
Vishwanath Venketaraman
author_sort Melissa Kelley
collection DOAJ
description BackgroundMycobacterium 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 findingsIn 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.ConclusionOur findings show that liposomal combination [R4W4] is a promising adjuvant therapy to increase M. avium susceptibility to known antibiotics.
format Article
id doaj-art-40a2b5e4ccdb4268bbac511d54a103a6
institution OA Journals
issn 2235-2988
language English
publishDate 2025-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cellular and Infection Microbiology
spelling doaj-art-40a2b5e4ccdb4268bbac511d54a103a62025-08-20T02:26:25ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-04-011510.3389/fcimb.2025.15473761547376The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium aviumMelissa Kelley0Kayvan Sasaninia1Ali Badaoui2Ira Glassman3Arbi Abnousian4Nadia Rai5Nadia Rai6Rakesh K. Tiwari7Rakesh K. Tiwari8Vishwanath Venketaraman9Department of Biomedical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United StatesDepartment of Biomedical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United StatesDepartment of Biomedical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United StatesDepartment of Biomedical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United StatesDepartment of Biomedical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United StatesDepartment of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA, United StatesDepartment of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, PakistanDepartment of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA, United StatesDepartment of Biomedical Sciences, College of Osteopathic Medicine of the Pacific-Northwest, Western University of Health Sciences, Lebanon, OR, United StatesDepartment of Biomedical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United StatesBackgroundMycobacterium 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 findingsIn 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.ConclusionOur findings show that liposomal combination [R4W4] is a promising adjuvant therapy to increase M. avium susceptibility to known antibiotics. https://www.frontiersin.org/articles/10.3389/fcimb.2025.1547376/fullMycobacterium aviumantimicrobialcyclic peptideantibioticsmacrophages
spellingShingle Melissa Kelley
Kayvan Sasaninia
Ali Badaoui
Ira Glassman
Arbi Abnousian
Nadia Rai
Nadia Rai
Rakesh K. Tiwari
Rakesh K. Tiwari
Vishwanath Venketaraman
The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium avium
Frontiers in Cellular and Infection Microbiology
Mycobacterium avium
antimicrobial
cyclic peptide
antibiotics
macrophages
title The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium avium
title_full The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium avium
title_fullStr The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium avium
title_full_unstemmed The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium avium
title_short The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival of Mycobacterium avium
title_sort effects of cyclic peptide r4w4 in combination with first line therapy on the survival of mycobacterium avium
topic Mycobacterium avium
antimicrobial
cyclic peptide
antibiotics
macrophages
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1547376/full
work_keys_str_mv AT melissakelley theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT kayvansasaninia theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT alibadaoui theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT iraglassman theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT arbiabnousian theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT nadiarai theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT nadiarai theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT rakeshktiwari theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT rakeshktiwari theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT vishwanathvenketaraman theeffectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT melissakelley effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT kayvansasaninia effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT alibadaoui effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT iraglassman effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT arbiabnousian effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT nadiarai effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT nadiarai effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT rakeshktiwari effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT rakeshktiwari effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium
AT vishwanathvenketaraman effectsofcyclicpeptider4w4incombinationwithfirstlinetherapyonthesurvivalofmycobacteriumavium