Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment

Acanthamoeba spp. are free-living parasites that can cause severe infections such as granulomatous amoebic encephalitis (GAE) and amoebic keratitis (AK). Polyhexamethylene biguanide (PHMB) is a topical application for AK treatment. However, PHMB is not entirely effective against all Acanthamoeba str...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Huang Jian-Ming, Ko Pin-Ju, Huang Chao-Li, Wen Po-Wei, Chen Chun-Hsien, Shih Min-Hsiu, Lin Wei-Chen, Huang Fu-Chin
Formato:	article
Lenguaje:	EN
Publicado:	EDP Sciences 2021
Materias:	acanthamoeba polyhexamethylene biguanide p450 monooxygenase amoebic keratitis Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/f8204af917ba44058fc5e31a93cc018d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f8204af917ba44058fc5e31a93cc018d
record_format	dspace
spelling	oai:doaj.org-article:f8204af917ba44058fc5e31a93cc018d2021-11-12T11:45:26ZCytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment1776-104210.1051/parasite/2021074https://doaj.org/article/f8204af917ba44058fc5e31a93cc018d2021-01-01T00:00:00Zhttps://www.parasite-journal.org/articles/parasite/full_html/2021/01/parasite210084/parasite210084.htmlhttps://doaj.org/toc/1776-1042Acanthamoeba spp. are free-living parasites that can cause severe infections such as granulomatous amoebic encephalitis (GAE) and amoebic keratitis (AK). Polyhexamethylene biguanide (PHMB) is a topical application for AK treatment. However, PHMB is not entirely effective against all Acanthamoeba strains or isolates. The mechanisms by which Acanthamoeba protects itself against extreme drug conditions without encystation are still unknown. According to a previous study, cytochrome P450 monooxygenase (CYP450MO) plays an important role in the oxidative biotransformation of numerous drugs related to metabolism. In this study, a CYP450MO fragment was inserted into the pGAPDH-EGFP vector and transfected into Acanthamoeba castellanii. We found that CYP450MO-overexpressing Acanthamoeba had higher survival rates than those of the control cells after PHMB treatment. Moreover, we also found that encystation-related genes such as cellulose synthase I (CSI), encystation-mediating serine proteinase (EMSP), and autophagy-related protein 8 (ATG8) expression levels were not significantly different between Acanthamoeba transfected by pGAPDH-EGFP or pGAPDH-EGFP-CYP450MO. We suggest that Acanthamoeba transfected by pGAPDH-EGFP-CYP450MO may not induce encystation-related genes to resist PHMB treatment. In conclusion, these findings indicate that CYP450MO may be an additional target when PHMB is used for treatment of amoebic keratitis.Huang Jian-MingKo Pin-JuHuang Chao-LiWen Po-WeiChen Chun-HsienShih Min-HsiuLin Wei-ChenHuang Fu-ChinEDP Sciencesarticleacanthamoebapolyhexamethylene biguanidep450 monooxygenaseamoebic keratitisInfectious and parasitic diseasesRC109-216ENParasite, Vol 28, p 77 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acanthamoeba polyhexamethylene biguanide p450 monooxygenase amoebic keratitis Infectious and parasitic diseases RC109-216
spellingShingle	acanthamoeba polyhexamethylene biguanide p450 monooxygenase amoebic keratitis Infectious and parasitic diseases RC109-216 Huang Jian-Ming Ko Pin-Ju Huang Chao-Li Wen Po-Wei Chen Chun-Hsien Shih Min-Hsiu Lin Wei-Chen Huang Fu-Chin Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment
description	Acanthamoeba spp. are free-living parasites that can cause severe infections such as granulomatous amoebic encephalitis (GAE) and amoebic keratitis (AK). Polyhexamethylene biguanide (PHMB) is a topical application for AK treatment. However, PHMB is not entirely effective against all Acanthamoeba strains or isolates. The mechanisms by which Acanthamoeba protects itself against extreme drug conditions without encystation are still unknown. According to a previous study, cytochrome P450 monooxygenase (CYP450MO) plays an important role in the oxidative biotransformation of numerous drugs related to metabolism. In this study, a CYP450MO fragment was inserted into the pGAPDH-EGFP vector and transfected into Acanthamoeba castellanii. We found that CYP450MO-overexpressing Acanthamoeba had higher survival rates than those of the control cells after PHMB treatment. Moreover, we also found that encystation-related genes such as cellulose synthase I (CSI), encystation-mediating serine proteinase (EMSP), and autophagy-related protein 8 (ATG8) expression levels were not significantly different between Acanthamoeba transfected by pGAPDH-EGFP or pGAPDH-EGFP-CYP450MO. We suggest that Acanthamoeba transfected by pGAPDH-EGFP-CYP450MO may not induce encystation-related genes to resist PHMB treatment. In conclusion, these findings indicate that CYP450MO may be an additional target when PHMB is used for treatment of amoebic keratitis.
format	article
author	Huang Jian-Ming Ko Pin-Ju Huang Chao-Li Wen Po-Wei Chen Chun-Hsien Shih Min-Hsiu Lin Wei-Chen Huang Fu-Chin
author_facet	Huang Jian-Ming Ko Pin-Ju Huang Chao-Li Wen Po-Wei Chen Chun-Hsien Shih Min-Hsiu Lin Wei-Chen Huang Fu-Chin
author_sort	Huang Jian-Ming
title	Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment
title_short	Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment
title_full	Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment
title_fullStr	Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment
title_full_unstemmed	Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment
title_sort	cytochrome p450 monooxygenase of acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment
publisher	EDP Sciences
publishDate	2021
url	https://doaj.org/article/f8204af917ba44058fc5e31a93cc018d
work_keys_str_mv	AT huangjianming cytochromep450monooxygenaseofacanthamoebacastellaniiparticipatesinresistancetopolyhexamethylenebiguanidetreatment AT kopinju cytochromep450monooxygenaseofacanthamoebacastellaniiparticipatesinresistancetopolyhexamethylenebiguanidetreatment AT huangchaoli cytochromep450monooxygenaseofacanthamoebacastellaniiparticipatesinresistancetopolyhexamethylenebiguanidetreatment AT wenpowei cytochromep450monooxygenaseofacanthamoebacastellaniiparticipatesinresistancetopolyhexamethylenebiguanidetreatment AT chenchunhsien cytochromep450monooxygenaseofacanthamoebacastellaniiparticipatesinresistancetopolyhexamethylenebiguanidetreatment AT shihminhsiu cytochromep450monooxygenaseofacanthamoebacastellaniiparticipatesinresistancetopolyhexamethylenebiguanidetreatment AT linweichen cytochromep450monooxygenaseofacanthamoebacastellaniiparticipatesinresistancetopolyhexamethylenebiguanidetreatment AT huangfuchin cytochromep450monooxygenaseofacanthamoebacastellaniiparticipatesinresistancetopolyhexamethylenebiguanidetreatment
_version_	1718430593418526720

Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment

Ejemplares similares