Determination of principal genotypic groups among susceptible, MDR and XDR clinical isolates of Mycobacterium tuberculosis in Belarus and Iran

Leonid P. TITOV, Manijeh KAHBAZI, Mohammad ARJOMANDZADEGAN, Larisa K. SURKOVA, Parisa FARNIA, Fatemeh SHEIKHOLESLAMI, Arezoo ESHGHINEJAD, Ali Asghar FARAZI, M. ESHRATI, Mana SHOJAPUR, Parviz OWLIA, Azam AHMADI

Abstract

Introduction: All members of the Mycobacterium tuberculosis complex were assigned to one of the three principle geneticgroups based on KatG463/GyrA95 polymorphism.Materials and Methods: A total of 202 isolates of M. tuberculosis consisting of 50 susceptible, 121 MDR (multidrug resis-tant) and 31 XDR (extensively drug resistant) isolated from culture-confirmed tuberculosis patients in different regions ofBelarus and Iran (Tehran and Markazi province). Isolates were screened by sequencing and polymerase chain reaction rest-riction fragment length polymorphism (RFLP) assay, and were further divided into three principal genetic groups (PGG),based on Sreevatsan s pattern as polymorphisms in KatG463/GyrA95 codons.Results: Among the 104 isolates, characterized as MDR from Belarus, 57 (54.8 ± 4.8%), 30 (28.8 ± 4.43%), 17 (16.3 ± 3.6),belonged to PGG 1, 2, and 3, respectively (p< 0.05). Thirty one XDR isolates from Belarus had a similar pattern as 15(48.4%), 12 (38.7%), 4 (12.9%) PGG 1, 2, and 3, respectively. From Iranian samples, Markazi isolates (susceptible todrugs) had a pattern as 12 (36.5%), 15 (45.5%), 3 (6%), and Tehran samples were (selected MDR): 9 (53%), 6 (35.2%), 2(11.8%) (PGG 1, 2, and 3, respectively). In a study of tuberculosis patients, who were in prison, no relation was foundbetween PGG and resistance to isoniazid, but most of the identified isolates belonged to PGG 1 (45.5 ± 10.9%) (p< 0.05).Overall, the group 1 isolates showed more frequency in MDR and XDR rather than susceptible strains, and there aren tany relations to geographic region.Conclusion: In susceptible strains, dominant forms were belonged to groups 2 and 3. It seems that PGG typing is closelyrelated to resistance status of isolates rather than geographic origin.

Özet

Giriş: Mycobacterium tuberculosis complexin tüm üyeleri KatG463/GyrA95 polimorfizmi temelinde üç temel genetik gruptanbirinde yer alır.Materyal ve Metod: Beyaz Rusya ve İran (Tahran ve Markazi)ın değişik bölgelerinden kültürle doğrulanmış tüberkülozluhastalardan 50si duyarlı, 121i MDR (çoklu ilaç direnci) ve 31i XDR (yaygın ilaç direnci) toplam 202 M. tuberculosis izo-latı izole edildi. İzolatlar, sequencing ve PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism)ile incelendi ve KatG463 GyrA95 kodonlarda polimorfizm ile Sreevatsans patterni temelinde üç ana genetik gruba (PGG)ayrıldı.Bulgular: Beyaz Rusyadan MDR olarak tanımlanan 104 izolattan 57 (%54.8 ± 4.8)si, 30 (%28.8 ± 4.43)u ve 17 (%16.3 ±3.6)si sırasıyla PGG1, 2 ve 3te yer alıyordu (p< 0.05). Beyaz Rusyadan 31 XDR, 15 (%48.4)i, 12 (%38.7)si, 4 (%12.9)üsırasıyla PGG 1, 2 ve 3te olmak üzere benzer bir patterne sahipti. İran örneklerinden, Markazi izolatları (ilaca duyarlı) 12(%36.5), 15 (%45.5), 3 (%6), ve Tahran örnekleri (seçilmiş MDR): 9 (%53), 6 (%35.2), 2 (%11.8) (PGG 1, 2 ve 3, sırasıyla) pa-ternine sahipti. Cezaevinde yatan tüberkülozlu hastalarda yapılan bir çalışmada, izoniazide direnç ile PGG arasında ilişkibulunmadı, ancak saptanan izolatların çoğu PGG 1de yer alıyordu (%45.5 ± 10.9) (p< 0.05). Genel olarak, grup 1 izolatla-rı, MDR ve XDRde duyarlı türlere göre daha sıktı ve coğrafik bölge ile ilişki yoktu. Sonuç: Duyarlı türlerde dominant form grup 2 ve 3te bulunuyordu. PGG grupları, coğrafik orijinden çok izolatların dirençdurumu ile ilişkili gibi görünmektedir.