A Novel Mutation in the Efflux Pump Rv۱۲۵۸c (Tap) Gene inMycobacterium tuberculosis Clinical Isolates Resistant to First-LineDrugs in Iran

Background and Aim : Tuberculosis (TB) remains a serious health problem worldwide, causingmillions of deaths annually. It is estimated that one-third of the world population is infected withlatent TB. Drug-resistant TB is considered a major and growing global threat. Despite the greatvariety of mutations in the resistance genes of Mycobacterium (M.) tuberculosis, the drugresistance mechanisms are still controversial. Recently, the presence of efflux pump genes in drugresistance was reported, adding to this complexity. Also, the increased expression of some effluxpump genes, such as Rv۱۲۵۸c, has been observed in the presence of antibiotics.Methods : We performed a molecular analysis Rv۱۲۵۸c gene in drug-resistant and sensitive (n =۵۳) clinical isolates by Polymerase chain reaction (PCR)-sequencing. All custom DNA ampliconswere sequenced, using both forward and reverse primers.Results : A novel Rv۱۲۵۸ gene mutation was found at Ala۱۴۸Thr in rifampicin monoresistantisolate ۱/۳۳ (۳%), as compared to the H۳۷Rv reference strain. Also, a cytosine nucleotide insertionwas found between positions ۵۸۰ and ۵۸۱ in ۲/۲۰ (۱۰%) drug-sensitive strains at identical genepositions.Conclusion : These results indicated the possibility of mutation in the efflux pump genes andsuggested the important role of Tap efflux pump genes in drug-resistant M. tuberculosis isolates.However, further research is required to determine the direct association of these mutations withresistant M. tuberculosis.

کلیدواژه ها:

Mycobacterium tuberculosis ، Molecular analysis ، Drug resistance ، efflux pump ، Rv۱۲۵۸c (Tap) gene