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Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis

Prior work has indicated that thymosin beta 4 (Tβ4) administered with ciprofloxacin markedly improves disease outcome for Pseudomonas aeruginosa (PA)-induced keratitis. As a result, the goal of the current study was to elucidate mechanisms by which Tβ4 mitigates the corneal response; specifically, r...

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Autores principales: Carion, Thomas W., Ebrahim, Abdul Shukkur, Alluri, Spandana, Ebrahim, Thanzeela, Parker, Tressa, Burns, Julia, Sosne, Gabriel, Berger, Elizabeth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555736/
https://www.ncbi.nlm.nih.gov/pubmed/32961846
http://dx.doi.org/10.3390/ijms21186840
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author Carion, Thomas W.
Ebrahim, Abdul Shukkur
Alluri, Spandana
Ebrahim, Thanzeela
Parker, Tressa
Burns, Julia
Sosne, Gabriel
Berger, Elizabeth A.
author_facet Carion, Thomas W.
Ebrahim, Abdul Shukkur
Alluri, Spandana
Ebrahim, Thanzeela
Parker, Tressa
Burns, Julia
Sosne, Gabriel
Berger, Elizabeth A.
author_sort Carion, Thomas W.
collection PubMed
description Prior work has indicated that thymosin beta 4 (Tβ4) administered with ciprofloxacin markedly improves disease outcome for Pseudomonas aeruginosa (PA)-induced keratitis. As a result, the goal of the current study was to elucidate mechanisms by which Tβ4 mitigates the corneal response; specifically, regarding its bactericidal influence and potential synergy with ciprofloxacin. An in vitro approach was carried out using minimum inhibitory concentration (MIC) assays to assess bactericidal activity against PA. In addition, antimicrobial peptide (AMP) production was evaluated at the mRNA levels using human corneal epithelial cells in response to lipopolysaccharide (LPS) challenge. The results of the MIC assays did not show direct bactericidal activity with Tβ4 alone, although ciprofloxacin exhibited significant killing at concentrations far lower than clinically dosed. Tβ4, however, displayed an indirect effect on bacterial killing, as shown by an upregulation of AMPs and related molecules. The cumulative data from this study indicate an indirect bactericidal role of Tβ4, as well as a synergistic relationship with ciprofloxacin. Furthermore, ciprofloxacin alone was found to influence cellular functions that otherwise have yet to be reported. These results highlight a mechanism of intracellular communication for Tβ4 and further strengthen its development as an adjunct therapy with antibiotics for corneal infections.
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spelling pubmed-75557362020-10-19 Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis Carion, Thomas W. Ebrahim, Abdul Shukkur Alluri, Spandana Ebrahim, Thanzeela Parker, Tressa Burns, Julia Sosne, Gabriel Berger, Elizabeth A. Int J Mol Sci Article Prior work has indicated that thymosin beta 4 (Tβ4) administered with ciprofloxacin markedly improves disease outcome for Pseudomonas aeruginosa (PA)-induced keratitis. As a result, the goal of the current study was to elucidate mechanisms by which Tβ4 mitigates the corneal response; specifically, regarding its bactericidal influence and potential synergy with ciprofloxacin. An in vitro approach was carried out using minimum inhibitory concentration (MIC) assays to assess bactericidal activity against PA. In addition, antimicrobial peptide (AMP) production was evaluated at the mRNA levels using human corneal epithelial cells in response to lipopolysaccharide (LPS) challenge. The results of the MIC assays did not show direct bactericidal activity with Tβ4 alone, although ciprofloxacin exhibited significant killing at concentrations far lower than clinically dosed. Tβ4, however, displayed an indirect effect on bacterial killing, as shown by an upregulation of AMPs and related molecules. The cumulative data from this study indicate an indirect bactericidal role of Tβ4, as well as a synergistic relationship with ciprofloxacin. Furthermore, ciprofloxacin alone was found to influence cellular functions that otherwise have yet to be reported. These results highlight a mechanism of intracellular communication for Tβ4 and further strengthen its development as an adjunct therapy with antibiotics for corneal infections. MDPI 2020-09-18 /pmc/articles/PMC7555736/ /pubmed/32961846 http://dx.doi.org/10.3390/ijms21186840 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Carion, Thomas W.
Ebrahim, Abdul Shukkur
Alluri, Spandana
Ebrahim, Thanzeela
Parker, Tressa
Burns, Julia
Sosne, Gabriel
Berger, Elizabeth A.
Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis
title Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis
title_full Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis
title_fullStr Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis
title_full_unstemmed Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis
title_short Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis
title_sort antimicrobial effects of thymosin beta-4 and ciprofloxacin adjunctive therapy in pseudomonas aeruginosa induced keratitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555736/
https://www.ncbi.nlm.nih.gov/pubmed/32961846
http://dx.doi.org/10.3390/ijms21186840
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