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...
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| Format: | Article |
| Language: | English |
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EDP Sciences
2021-01-01
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| Series: | Parasite |
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| Online Access: | https://www.parasite-journal.org/articles/parasite/full_html/2021/01/parasite210084/parasite210084.html |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T14:03:49Z |
| format | Article |
| id | doaj.art-f8204af917ba44058fc5e31a93cc018d |
| institution | Directory Open Access Journal |
| issn | 1776-1042 |
| language | English |
| last_indexed | 2024-03-11T14:03:49Z |
| publishDate | 2021-01-01 |
| publisher | EDP Sciences |
| record_format | Article |
| series | Parasite |
| spelling | doaj.art-f8204af917ba44058fc5e31a93cc018d2023-11-02T03:49:36ZengEDP SciencesParasite1776-10422021-01-01287710.1051/parasite/2021074parasite210084Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatmentHuang Jian-Ming0Ko Pin-Ju1Huang Chao-Li2Wen Po-Wei3Chen Chun-Hsien4Shih Min-Hsiu5Lin Wei-Chenhttps://orcid.org/0000-0001-7223-5931Huang Fu-Chin6Department of Parasitology, College of Medicine, National Cheng Kung UniversityDepartment of Microbiology and Immunology, College of Medicine, National Cheng Kung UniversityInstitute of Tropical Plant Sciences and Microbiology, National Cheng Kung UniversitySchool of Medicine, College of Medicine, National Cheng Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityDepartment of Ophthalmology, National Cheng Kung University HospitalDepartment of Ophthalmology, National Cheng Kung University HospitalAcanthamoeba 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.https://www.parasite-journal.org/articles/parasite/full_html/2021/01/parasite210084/parasite210084.htmlacanthamoebapolyhexamethylene biguanidep450 monooxygenaseamoebic keratitis |
| spellingShingle | 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 Parasite acanthamoeba polyhexamethylene biguanide p450 monooxygenase amoebic keratitis |
| title | 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_short | 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 |
| topic | acanthamoeba polyhexamethylene biguanide p450 monooxygenase amoebic keratitis |
| url | https://www.parasite-journal.org/articles/parasite/full_html/2021/01/parasite210084/parasite210084.html |
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