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Abstrak :
[Penicillium marneffei merupakan fungi patogen yang ditemukan di Asia Tenggara, khususnya Thailand. Penisiliosis dapat menyebabkan mikosis sistemik sehingga membahayakan nyawa penderita immunocompromised, khususnya penderita HIV/AIDS. Antifungi seperti Fluconazole dan Ketoconazole, digunakan untuk mengatasi infeksi P. marneffei. Akan tetapi, penggunaan antifungi secara jangka panjang dapat memicu kemungkinan munculnya mutan resisten P. marneffei. Resistensi pada fungi dapat dipengaruhi beberapa faktor, salah satunya, overekspresi transporter pengeluaran obat (drug efflux transporter). Mekanisme pompa pengeluaran obat diatur oleh berbagai transporter. Transporter yang paling umum diketahui ialah transporter ABC (ATP-binding-cassette) dan MFS (Major Facilitator Superfamily). Transporter ABC multidrug (MDR) pada P. marneffei telah dipelajari dengan baik, sedangkan transporter MFS MDR pada fungi tersebut, belum mendapatkan perhatian yang sama. Penelitian ini fokus pada satu transporter MFS MDR P. marneffei, yakni PMAA 067100, yang diekspresikan pada Saccharomyces cerevisiae ADΔ; sistem ekspresi yang sangat rentan terhadap berbagai macam antifungi. Pengamatan melalui mikroskop konfokal dan uji Disk Diffusion menunjukkan bahwa transporter PMAA 067100 terlokalisasi pada membran sel S. cerevisiae ADΔ dan resisten terhadap Fluconazole dan Terbinafine.;Penicillium marneffei has been known as a pathogenic fungi which is found in Southeast Asia, especially Thailand. The infection by this fungi recognized as Penicilliosis, that caused systemic mycosis, might be lethal in immunocompromised patient, specifically HIV/AIDS patient. Antifungal such as Fluconazole and Ketoconazole, had been used against P. marneffei infection. However, the long-term-use of antifungal might cause an emerging resistant strain of P. marneffei. The resistance phenomenon in fungi is caused by several factors, one of it is the overexpression of drug efflux transporter. Mechanism of this efflux pump is regulated by some of transporters such as ABC (ATP-binding-cassette) and MFS (Major Facilitator Superfamily) transporter. The ABC multidrug (MDR) transporter of P. marneffei has been studied well, yet the underrated MFS MDR transporter of the same fungi has not received the same attention. This study focus on one of P. marneffei MFS MDR transporter, known as PMAA 067100, which was expressed in Saccharomyces cerevisiae ADΔ; an expression system which is very susceptible to many kind of antifungal. Observation through confocal microscope and Disk Diffusion test showed that PMAA 067100 transporter was localized in S. cerevisiae ADΔ cell membrane and resistant against Fluconazole and Terbinafine., Penicillium marneffei has been known as a pathogenic fungi which is found in Southeast Asia, especially Thailand. The infection by this fungi recognized as Penicilliosis, that caused systemic mycosis, might be lethal in immunocompromised patient, specifically HIV/AIDS patient. Antifungal such as Fluconazole and Ketoconazole, had been used against P. marneffei infection. However, the long-term-use of antifungal might cause an emerging resistant strain of P. marneffei. The resistance phenomenon in fungi is caused by several factors, one of it is the overexpression of drug efflux transporter. Mechanism of this efflux pump is regulated by some of transporters such as ABC (ATP-binding-cassette) and MFS (Major Facilitator Superfamily) transporter. The ABC multidrug (MDR) transporter of P. marneffei has been studied well, yet the underrated MFS MDR transporter of the same fungi has not received the same attention. This study focus on one of P. marneffei MFS MDR transporter, known as PMAA 067100, which was expressed in Saccharomyces cerevisiae ADΔ; an expression system which is very susceptible to many kind of antifungal. Observation through confocal microscope and Disk Diffusion test showed that PMAA 067100 transporter was localized in S. cerevisiae ADΔ cell membrane and resistant against Fluconazole and Terbinafine.]

Abstrak :
Kandidiasis invasif yang disebabkan oleh Candida krusei merupakan salah satu penyebab kematian dengan angka kematian yang tinggi. Terjadinya resistansi terhadap flukonazol dilaporkan terkait dengan gen penanda resistansi intrinsik. Data epidemiologi molekular dengan Whole Genome Sequencing (WGS) yang mengidentifikasi gen dan varian yang terkait virulensi dan resistansi obat Candida krusei belum pernah dilaporkan di Jakarta, maupun di Indonesia. Berdasarkan permasalahan di atas, dilakukan penelitian lebih lanjut untuk menentukan profil gen resistansi dengan metode Whole Genome Sequencing. Hasil pemetaan MLST diperoleh ada 6 housekeeping gen yaitu ADE2, HIS3, LEU2, LYS2D, NMT1 dan TRP1. Berdasarkan hasil variant calling ditemukan beberapa gen yang berperan dalam resistansi yaitu ERG11 dan FKS1. Mutasi yang ditemukan meliputi missense, synonymous, stop gain dan indel. Sebagian besar adalah varian mutasi missense dan synonymous. Pola kepekaan Candida krusei dengan metode difusi cakram sebagian besar terdiri dari isolat yang resisten dan sensitif terhadap beberapa antijamur seperti flukonazol, itrakonazol, ketonazol, amfoterisin B, nistatin, vorikonazol dan mikonazol. ......Invasive candidiasis caused by Candida krusei is one of the causes of death with a high mortality rate. The occurrence of resistance to fluconazole is reported to be related to intrinsic resistance marker genes. Molecular epidemiological data related to Whole Genome Sequencing (WGS) that identify genes and variants associated with Candida krusei virulence and drug resistance have never been reported in Jakarta, nor in Indonesia. Based on the problems above, further research was carried out to determine the resistance gene profile using the Whole Genome Sequencing method. The results of the MLST mapping showed that there were 6 housekeeping genes namely ADE2, HIS3, LEU2, LYS2D, NMT1, and TRP1. Based on the results of variant calling, several genes that play a role in resistance were found, namely ERG11 and FKS1. The mutations found include missense, synonymous, stop gain, and indel. Most are missense and synonymous mutation variants. The sensitivity pattern of Candida krusei by disc diffusion method mostly consisted of isolates that were resistant and sensitive to several antifungals such as fluconazole, itraconazole, ketoconazole, amphotericin B, nystatin, voriconazole, and miconazole.

Abstrak :
Candida sp. Berbagai spesies Candida seperti; C.albicans, C.glabrata, C,parapsilosis, C.tropicalis, C.keyfr, C.lusitaniae dan C.krusei. Saat ini, kandidiasis meningkat akibat tingginya individu dengan defisiensi imun, penyakit kronik, transplantasi dan faktor lainnya. Beberapa obat dilaporkan mengalami resistensi. Fluconazole merupakan salah satu lini pertama pada kandidiasis. Beberapa studi melaporkan fluconazole mengalami resistensi terhadap C. krusei. Voriconazole merupakan golongan azole terbaru yang mempunyai sensitifitas lebih tinggi terhadap C.krusei. Tujuan: Penelitian ini bertujuan untuk mengetahui sensitifitas fluconazole dan voriconazole terhadap C.krusei Metode: Penelitian ini menggunakan data sekunder dari rekam medik pasien kandidiasis di RSCM tahun 2013-2018 yang sudah diuji difusi cakram untuk pengujian sensitifitas dengan total sampel adalah 249. Hasil: Uji sensitifitas menunjukkan perbedaan yang bermakna antara fluconazole dengan voriconazole dengan rincian 191 isolat diuji dengan fluconazole 50.26% sensitif, 2.09% Susceptible Dose Dependent (SDD), dan 47.64% resisten sementara dengan voriconazole menunjukkan 100% sensitif dari 58 sampel (p< 0.05). Hasil dari penelitian, voriconazole lebih sensitif dari fluconazole terhadap Candida krusei. Kesimpulan: C.krusei lebih sensitif terhadap voriconazole karena memiliki kemampuan resistensi secara intrinsik terhadap fluconazole.
Candida sp. Various species of Candida such as; C. albicans, C. glabrata, C. parapsilosis, C. tropicalalis, C. keyfr, C. lusitaniae and C. krusei. Currently, candidiasis is increasing due to the high number of individuals with immunodeficiency, chronic disease, transplantation and other factors. Several drugs have been reported to be resistant. Fluconazole is one of the the first line of treatment for candidiasis. Several studies reported that fluconazole was resistant to C. krusei. Voriconazole is the newest azole group that has a higher sensitivity to C. krusei. Objective: This study aims to determine the sensitivity of fluconazole and voriconazole to C.krusei Methods: This study used secondary data from the medical records of candidiasis patients at the RSCM in 2013-2018 which had been tested for disc diffusion for sensitivity testing with a total sample of 249. Results: Test sensitivity showed a significant difference between fluconazole and voriconazole with details of 191 isolates tested with fluconazole 50.26% sensitive, 2.09% Susceptible Dose Dependent (SDD), and 47.64% resistant while with voriconazole showed 100% sensitivity from 58 samples (p < 0.05). The results of the study, voriconazole more sensitive than fluconazole to Candida krusei. Conclusion: C. krusei is more sensitive to voriconazole because it has the ability to intrinsic resistance to fluconazole.