Rifabutin Cross-resistance and Associated rpoB Mutations in Rifampicin-resistant Mycobacterium tuberculosis Complex Isolates
- 1Clinic of Medical Microbiology, Manisa City Hospital, Manisa, Türkiye
- 2Department of Medical Microbiology, Manisa Celal Bayar University Faculty of Medicine, Manisa, Türkiye
Abstract
OBJECTIVE: This study aimed to phenotypically evaluate rifabutin susceptibility in rifampicin-resistant Mycobacterium tuberculosis complex isolates and to identify, through DNA sequence analysis of the rifampicin resistance-determining region (RRDR), specific rpoB mutations associated with rifabutin susceptibility.
MATERIAL AND METHODS: A total of 43 rifampicin-resistant and 23 rifampicin-susceptible (control) Mycobacterium tuberculosis complex isolates, collected between 2000 and 2020 at the Mycobacteriology Laboratories of Manisa Celal Bayar University and Ege University Faculty of Medicine, were included. Phenotypic drug susceptibility testing was performed using the MGIT 960 system. Mutations in a 682-bp fragment encompassing the 81-bp RRDR of the rpoB gene were investigated by Sanger sequencing.
RESULTS: Among the 43 rifampicin-resistant isolates, 39 (91%) were resistant to rifabutin, while four (9%) remained susceptible. All rifampicin-susceptible isolates were also susceptible to rifabutin. A total of 44 non-synonymous single nucleotide polymorphisms were detected in rifampicin-resistant isolates, whereas no mutations were observed in the control group. Seven distinct mutation patterns were identified, including one isolate with a double mutation. The most common mutations were S531L (76%), H526Y (12%), and D516Y (4%). The mutations D516Y, L511P, and L533P, as well as the M515I+D516Y double mutation, were associated with rifabutin susceptibility.
CONCLUSION: Early identification of rpoB mutations associated with rifabutin susceptibility may allow substitution of rifampicin with rifabutin in selected rifampicin-resistant cases, potentially improving treatment outcomes and limiting the emergence of resistance to second-line drugs. Further in vitro studies, including minimum inhibitory concentration testing, and additional clinical data on rifabutin-containing regimens are needed.
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BibTeX
@article{surucuoglu2026rifabutin,
title = {{Rifabutin Cross-resistance and Associated rpoB Mutations in Rifampicin-resistant Mycobacterium tuberculosis Complex Isolates}},
author = {Nalan Sürücüoğlu and Süheyla Sürücüoğlu and Nuri Özkütük},
journal = {Thoracic Research and Practice},
year = {2026},
month = nov,
doi = {10.4274/thoracrespract.2026.2026-1-16},
url = {https://doi.org/10.4274/thoracrespract.2026.2026-1-16},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Rifabutin Cross-resistance and Associated rpoB Mutations in Rifampicin-resistant Mycobacterium tuberculosis Complex Isolates
AU - Nalan Sürücüoğlu
AU - Süheyla Sürücüoğlu
AU - Nuri Özkütük
PY - 2026
DA - 2026/11/03
JO - Thoracic Research and Practice
DO - 10.4274/thoracrespract.2026.2026-1-16
UR - https://doi.org/10.4274/thoracrespract.2026.2026-1-16
AB - OBJECTIVE: This study aimed to phenotypically evaluate rifabutin susceptibility in rifampicin-resistant Mycobacterium tuberculosis complex isolates and to identify, through DNA sequence analysis of the rifampicin resistance-determining region (RRDR), specific rpoB mutations associated with rifabutin susceptibility. MATERIAL AND METHODS: A total of 43 rifampicin-resistant and 23 rifampicin-susceptible (control) Mycobacterium tuberculosis complex isolates, collected between 2000 and 2020 at the Mycobacteriology Laboratories of Manisa Celal Bayar University and Ege University Faculty of Medicine, were included. Phenotypic drug susceptibility testing was performed using the MGIT 960 system. Mutations in a 682-bp fragment encompassing the 81-bp RRDR of the rpoB gene were investigated by Sanger sequencing. RESULTS: Among the 43 rifampicin-resistant isolates, 39 (91%) were resistant to rifabutin, while four (9%) remained susceptible. All rifampicin-susceptible isolates were also susceptible to rifabutin. A total of 44 non-synonymous single nucleotide polymorphisms were detected in rifampicin-resistant isolates, whereas no mutations were observed in the control group. Seven distinct mutation patterns were identified, including one isolate with a double mutation. The most common mutations were S531L (76%), H526Y (12%), and D516Y (4%). The mutations D516Y, L511P, and L533P, as well as the M515I+D516Y double mutation, were associated with rifabutin susceptibility. CONCLUSION: Early identification of rpoB mutations associated with rifabutin susceptibility may allow substitution of rifampicin with rifabutin in selected rifampicin-resistant cases, potentially improving treatment outcomes and limiting the emergence of resistance to second-line drugs. Further in vitro studies, including minimum inhibitory concentration testing, and additional clinical data on rifabutin-containing regimens are needed.
SN - 2979-9139
ER -