Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis

Pseudomonas aeruginosa is an opportunistic pathogen and a major cause of corneal infections worldwide. The bacterium secretes several toxins through its type III secretion system (T3SS) to subvert host immune responses. In addition, it is armed with intrinsic as well as acquired antibiotic resistanc...

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Autores principales:	Prerana Sharma, Mikael Elofsson, Sanhita Roy
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	antimicrobial peptides type iii secretion system pseudomonas aeruginosa reactive oxygen species corneal epithelial cells inp0341 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/648dcdc034394af08a76c27fd233b9f0
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spelling	oai:doaj.org-article:648dcdc034394af08a76c27fd233b9f02021-11-17T14:21:58ZAttenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis2150-55942150-560810.1080/21505594.2020.1776979https://doaj.org/article/648dcdc034394af08a76c27fd233b9f02020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1776979https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Pseudomonas aeruginosa is an opportunistic pathogen and a major cause of corneal infections worldwide. The bacterium secretes several toxins through its type III secretion system (T3SS) to subvert host immune responses. In addition, it is armed with intrinsic as well as acquired antibiotic resistance mechanisms that make treatment a significant challenge and new therapeutic interventions are needed. Type III secretion inhibitors have been studied as an alternative or in accompaniment to traditional antibiotics to inhibit virulence of bacteria. In this study, INP0341, a T3SS inhibitor, inhibited cytotoxicity by P. aeruginosa toward human corneal epithelial cells (HCEC) at 100 μM without affecting bacterial growth in the liquid media. An increased expression of antimicrobial peptides and reactive oxygen species generation was also observed in cells exposed to P. aeruginosa in the presence of INP0341. Furthermore, INP0341 efficiently attenuated corneal infection by P. aeruginosa in an experimental model of murine keratitis as evident from corneal opacity, clinical score and bacterial load. Thus, INP0341 appears to be a promising candidate to treat corneal infection caused by P. aeruginosa and can be further considered as an alternative therapeutic intervention.Prerana SharmaMikael ElofssonSanhita RoyTaylor & Francis Grouparticleantimicrobial peptidestype iii secretion systempseudomonas aeruginosareactive oxygen speciescorneal epithelial cellsinp0341Infectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 795-804 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antimicrobial peptides type iii secretion system pseudomonas aeruginosa reactive oxygen species corneal epithelial cells inp0341 Infectious and parasitic diseases RC109-216
spellingShingle	antimicrobial peptides type iii secretion system pseudomonas aeruginosa reactive oxygen species corneal epithelial cells inp0341 Infectious and parasitic diseases RC109-216 Prerana Sharma Mikael Elofsson Sanhita Roy Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis
description	Pseudomonas aeruginosa is an opportunistic pathogen and a major cause of corneal infections worldwide. The bacterium secretes several toxins through its type III secretion system (T3SS) to subvert host immune responses. In addition, it is armed with intrinsic as well as acquired antibiotic resistance mechanisms that make treatment a significant challenge and new therapeutic interventions are needed. Type III secretion inhibitors have been studied as an alternative or in accompaniment to traditional antibiotics to inhibit virulence of bacteria. In this study, INP0341, a T3SS inhibitor, inhibited cytotoxicity by P. aeruginosa toward human corneal epithelial cells (HCEC) at 100 μM without affecting bacterial growth in the liquid media. An increased expression of antimicrobial peptides and reactive oxygen species generation was also observed in cells exposed to P. aeruginosa in the presence of INP0341. Furthermore, INP0341 efficiently attenuated corneal infection by P. aeruginosa in an experimental model of murine keratitis as evident from corneal opacity, clinical score and bacterial load. Thus, INP0341 appears to be a promising candidate to treat corneal infection caused by P. aeruginosa and can be further considered as an alternative therapeutic intervention.
format	article
author	Prerana Sharma Mikael Elofsson Sanhita Roy
author_facet	Prerana Sharma Mikael Elofsson Sanhita Roy
author_sort	Prerana Sharma
title	Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis
title_short	Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis
title_full	Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis
title_fullStr	Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis
title_full_unstemmed	Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis
title_sort	attenuation of pseudomonas aeruginosa infection by inp0341, a salicylidene acylhydrazide, in a murine model of keratitis
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/648dcdc034394af08a76c27fd233b9f0
work_keys_str_mv	AT preranasharma attenuationofpseudomonasaeruginosainfectionbyinp0341asalicylideneacylhydrazideinamurinemodelofkeratitis AT mikaelelofsson attenuationofpseudomonasaeruginosainfectionbyinp0341asalicylideneacylhydrazideinamurinemodelofkeratitis AT sanhitaroy attenuationofpseudomonasaeruginosainfectionbyinp0341asalicylideneacylhydrazideinamurinemodelofkeratitis
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Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis

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