KatG mutations in isoniazid-resistant strains of Mycobacterium tuberculosis isolates from Belarusian patients

Bu çalışmada Belaruslu hastalardan izole edilen Mycobacterium tuberculosis’te katG mutasyonlarının sıklığı, tipi ve lokalizasyonunu belirlemeyi hedefledik. Belaruslu hastalarda katalaz peroksidaz (katG) genindeki iki farklı kodona ait mutasyonların izoniazide karşı direnç gelişimine yol açtığı gösterildi. Belarus’un farklı bölgelerinden tolam 42 Rif-r ve Inhr (MDR) zinciri elde edildi. Yapılan kültür duyarlılık testlerinde bütün bu 42 zincirin de streptomisine (%90) dirençli olduğu, 16 zincirin ise etambutole (%43) dirençli olduğu bulundu. DNA ekstraksiyonu, standart PCR ve katG geni amplifikasyonu yöntemleri kullanıldı. En fazla etkilenen katG kodonları 315 (%95), 316 (%16.2) ve 309 (%14.5) idi. 315 numaralı kodonda dört tip mutasyon görüldü: AGCACC (n= 36) %32.4, AGCAGG (n= 1) %0.9, AGCAAC (n= 2) %1.8, AGCGGC (n= 1) %0.9. 316 numaralı kodonda bir tane mutasyon görülürken; GGCAGC (n= 18) %16.2, 309 no’lu kodonda toplam 4 mutasyon vardı: GGTGGT (n= 7) %6.3, GGTGCT (n= 4) %3.6, GGTGTC (n= 3) %2.7, GGTGGG (n= 1) %0.9. Gösterilen mutasyonların %34’ü 309 no’lu kodona, %37’si 316 no’lu kodona, %29’u ise diğer kodonlara aitti. 463 ve 35 numaralı kodonlarda 2 farklı zincir mutasyonu bulunurken, 454 ve 357 numaralı kodonlarda ise hiçbir mutasyona rastlanmamıştır. Sonuç olarak bütün INH-r MBT’lerdeki direnç 315 no’lu kodondaki nükleotid değişiklikleri ile ilişkilidir.

Belaruslu hastalardan izole edilen izoniazide dirençli Mycobacterium tuberculosis’lerdeki katG mutasyonları

The aim of this study was to investigate the frequency, location and type of katG mutations in Mycobacterium tuberculosis strains isolated from patients in Belarus. Mutations in different codons causing resistance to isoniazide in the gene of catalase peroxides (katG) in Belarusian strains was determined. 42 strains of Rif-r and Inhr(MDR) were isolated in different regions of Belarus. Culture susceptibility testing of all 42 strains revealed resistance to streptomycin (90%), 16 strains (43%) were resistant to etambutol. DNA Extraction, Standard PCR identification and katG gene amplification were performed. The most affected codons of katG gene were 315(95%), 316(16.2%), and 309(14.5%). Four types of mutations were identified in codon 315: AGC→ACC (n=36)32.4%, AGC→AGG (n=1) 0.9%, AGC→AAC (n=2) 1.8%, AGC→GGC (n=1) 0.9%. One type of mutation was found in codon 316: GGC→AGC (n=18)16.2%, four types of mutations were detected in codon 309: GGT→GGT (n=7)6.3%, GGT→GCT (n=4)3.6%, GGT→GTC (n=3)2.7%, GGT→GGG (n=1)0.9%. Mutations in codon 309 make up 34%, in codon 316 (37%) and other types of mutations 29% of all detected mutations. In 2 isolated strains mutation were identified in codons 463, 35 and, in codons 454, 357 respectively and 2 isolates, there wasn’t fount any mutations. Concluding, all INH–r MBT had resistance-associated nucleotide changes mostly in codons 315.

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