Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları
Yıl: 2023 Cilt: 57 Sayı: 1 Sayfa Aralığı: 45 - 59 Metin Dili: Türkçe DOI: 10.5578/mb.202399004 İndeks Tarihi: 05-05-2023
Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları
Öz: Etambutol (EMB), Mycobacterium tuberculosis kompleksi (MTC)’nin neden olduğu tüberküloz (TB) hastalığının standart kombinasyon tedavisinde kullanılan birinci seçenek ilaçlardan biridir ve tedavide anahtar rol oynayan ilaçlara karşı direnç dünya genelinde artmaktadır. EMB direncinden, embCAB opero- nundaki dirençle ilişkisi doğrulanmış mutasyonlar sorumlu tutulmaktadır. Bu çalışmada, fenotipik olarak EMB’ye dirençli ve duyarlı olduğu saptanan klinik MTC izolatlarında embA, embB ve embC gen bölge- lerinde meydana gelen mutasyonların sıklığının ve paternlerinin belirlenmesi amaçlanmıştır. Çalışmaya geleneksel fenotipik ilaç duyarlılık testi ile EMB dirençli 44 ve EMB, izoniyazid, rifampisin ve streptomisine duyarlı 20 olmak üzere toplamda 64 adet MTC izolatı dahil edilmiştir. DNA izolasyonu sonrası, EMB direnci ile ilişkili embA, embB ve embC gen bölgeleri özgül primer dizileri ile amplifiye edilmiştir. Elde edilen PCR amplifikasyon ürünleri, ‘Bigdye Terminator v3.1 Cycle Sequencing kit’ (Applied Biosystems, ABD) kullanılarak döngü dizileme yapılmıştır. Reaksiyon ürünlerinin elektroforez işlemi ABI PRISM 3130XL Genetic Analyzer (Applied Biosystems, ABD) otomatize DNA dizi analizi cihazında gerçekleştirilmiştir. Dizi analizi verileri çoklu dizi analiz programlarında hizalanarak mutasyona uğramış gen bölgeleri belirlenmiş- tir. Çalışmada EMB dirençli izolatların %68.2 (30/44)’sinde embCAB operonunda genomik mutasyonlarsaptanmıştır. Dirençli izolatların %66 (29/44)’sında embB gen bölgesinde mutasyon saptanmış olup, bu mutasyonların %76 (22/29)’sının 306. kodon pozisyonunda olduğu ve bu kodonda en yaygın saptanan mutasyon paternlerinin ATG→GTG (M306V; %58.6; 17/29), ATG→ATA, ATC veya ATT (M306I; %17.2; 5/29)’ye dönüşüm şeklinde olduğu belirlenmiştir. embB gen gölgesinde saptan diğer mutasyonlar; Y334H (%3.4; 1/29), D354A (%6.9; 2/29), E378A (%3.4; 1/29), G406C (%3.4; 1/29), M423I (%3.4; 1/29) ve E521A (%3.4; 1/29) olarak belirlenmiştir. EMB dirençli 44 izolatın birinde (%2.3) embA gen bölgesinde (L330L) ve ikisinde (%4.5) embC gen bölgesinde (bir izolatta T270I ve diğer izolatta T270I ve E305E) mu- tasyon saptanmıştır. Fenotipik olarak EMB duyarlı izolatların ise sadece birinde (%5) embA gen bölgesinde (E180G) mutasyon saptanmıştır. Yaptığımız çalışmada EMB dirençli MTC izolatlarında mutasyonların sık- lıkla embB geni 306. kodonda oluştuğu tespit edilmiştir ve EMB direncinin gelişmesinde bu mutasyonun potansiyel rolü bulunmaktadır. Ancak mutasyonların olmamasının fenotipik EMB direncini dışlamayacağı sonucuna varılmıştır. Sonuçlar, ülkemizde EMB direncine neden olan embCAB operonu mutasyonlarının moleküler epidemiyolojisinin aydınlatılmasına ışık tutacaktır.
Anahtar Kelime: The Mutations on embA, embB and embC Gene Region in Ethambutol-Resistant and Susceptible Clinical Mycobacterium tuberculosis Complex Isolates
Öz: Ethambutol (EMB) is one of the first-line drugs used in the standard combination therapy for tuberculo- sis (TB) caused by Mycobacterium tuberculosis complex (MTC), and resistance to drugs that play a key role in treatment is increasing worldwide. Mutations in the embCAB operon that have been confirmed to be associated with resistance are responsible for EMB resistance. In this study, it was aimed to determine the frequency and patterns of mutations in embA, embB and embC gene regions in clinical MTC isolates found to be phenotypically resistant and susceptible to EMB. A total of 64 MTC isolates, 44 of resistant to EMB and 20 of susceptible to EMB, isoniazid, rifampicin, and streptomycin by conventional phenotypic drug susceptibility test, were included in the study. Following the DNA isolation, embA, embB and embC gene regions associated with EMB resistance were amplified with specific primer sequences. The PCR products were cycle sequenced using the Bigdye Terminator v3.1 Cycle Sequencing kit (Applied Biosystems, USA) and electrophoretically separated on the ABI PRISM 3130XL Genetic Analyzer (Applied Biosystems, USA). Mutated gene regions were identified by aligning sequence analysis data in multiple sequence analysis programs. In the study, genomic mutations in the embCAB operon were detected in 68.2% (30/44) of the EMB resistant isolates. Mutations in the embB gene region were detected in 66% (29/44) of the resistant isolates, 76% (22/29) of these mutations were at codon 306 and the most common mutation patterns in this codon were determined as ATG→GTG (M306V; 58.6%; 17/29), ATG→ATA, ATC or ATT (M306I; 17.2%; 5/29). Other mutations in the embB gene region were determined as Y334H (3.4%; 1/29), D354A (6.9%; 2/29), E378A (3.4%; 1/29), G406C (3.4%; 1/29), M423I (3.4%; 1/29) and E521A (3.4%; 1/29). Of the 44 EMB-resistant isolates, mutations were detected in one (2.3%) of the isolate in the embA gene region (L330L) and in two (4.5%) of the isolates in the embC gene region (T270I in one isolate and T270I and E305E in the other isolate). Of the phenotypically EMB susceptible isolates, mutation was detected in only one (5%) of the isolates in the embA gene region (E180G). In our study, it was determined that muta- tions frequently occur in codon 306 of the embB gene in EMB-resistant MTC isolates and this mutation has a potential role in the development of EMB resistance. However, it was concluded that the absence of mutations does not exclude phenotypic EMB resistance. Our results will shed light on the molecular epidemiology of embCAB operon mutations that cause EMB resistance in our country.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Bibliyografik
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| APA | Kurnaz N, Tezcan Ülger S, ULGER M, arslanturk a, ASLAN G, KÖKSAL f (2023). Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. , 45 - 59. 10.5578/mb.202399004 |
| Chicago | Kurnaz Nurbanu,Tezcan Ülger Seda,ULGER Mahmut,arslanturk ahmet,ASLAN GÖNÜL,KÖKSAL fatih Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. (2023): 45 - 59. 10.5578/mb.202399004 |
| MLA | Kurnaz Nurbanu,Tezcan Ülger Seda,ULGER Mahmut,arslanturk ahmet,ASLAN GÖNÜL,KÖKSAL fatih Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. , 2023, ss.45 - 59. 10.5578/mb.202399004 |
| AMA | Kurnaz N,Tezcan Ülger S,ULGER M,arslanturk a,ASLAN G,KÖKSAL f Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. . 2023; 45 - 59. 10.5578/mb.202399004 |
| Vancouver | Kurnaz N,Tezcan Ülger S,ULGER M,arslanturk a,ASLAN G,KÖKSAL f Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. . 2023; 45 - 59. 10.5578/mb.202399004 |
| IEEE | Kurnaz N,Tezcan Ülger S,ULGER M,arslanturk a,ASLAN G,KÖKSAL f "Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları." , ss.45 - 59, 2023. 10.5578/mb.202399004 |
| ISNAD | Kurnaz, Nurbanu vd. "Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları". (2023), 45-59. https://doi.org/10.5578/mb.202399004 |
| APA | Kurnaz N, Tezcan Ülger S, ULGER M, arslanturk a, ASLAN G, KÖKSAL f (2023). Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. Mikrobiyoloji Bülteni, 57(1), 45 - 59. 10.5578/mb.202399004 |
| Chicago | Kurnaz Nurbanu,Tezcan Ülger Seda,ULGER Mahmut,arslanturk ahmet,ASLAN GÖNÜL,KÖKSAL fatih Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. Mikrobiyoloji Bülteni 57, no.1 (2023): 45 - 59. 10.5578/mb.202399004 |
| MLA | Kurnaz Nurbanu,Tezcan Ülger Seda,ULGER Mahmut,arslanturk ahmet,ASLAN GÖNÜL,KÖKSAL fatih Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. Mikrobiyoloji Bülteni, vol.57, no.1, 2023, ss.45 - 59. 10.5578/mb.202399004 |
| AMA | Kurnaz N,Tezcan Ülger S,ULGER M,arslanturk a,ASLAN G,KÖKSAL f Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. Mikrobiyoloji Bülteni. 2023; 57(1): 45 - 59. 10.5578/mb.202399004 |
| Vancouver | Kurnaz N,Tezcan Ülger S,ULGER M,arslanturk a,ASLAN G,KÖKSAL f Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları. Mikrobiyoloji Bülteni. 2023; 57(1): 45 - 59. 10.5578/mb.202399004 |
| IEEE | Kurnaz N,Tezcan Ülger S,ULGER M,arslanturk a,ASLAN G,KÖKSAL f "Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları." Mikrobiyoloji Bülteni, 57, ss.45 - 59, 2023. 10.5578/mb.202399004 |
| ISNAD | Kurnaz, Nurbanu vd. "Etambutole Dirençli ve Duyarlı Mycobacterium tuberculosis Kompleksi Klinik İzolatlarında embA, embB ve embC Gen Bölgesi Mutasyonları". Mikrobiyoloji Bülteni 57/1 (2023), 45-59. https://doi.org/10.5578/mb.202399004 |
