Mycobacterium Kansasii İzolatlarında İlaç Direnç Profili ve İlgili Gen Mutasyonları

Abstract

Nontuberculous mycobacteria (NTM) are predominantly environmental bacteria that are categorized into two groups based on their growth rates: slow-growing and rapid-growing NTM. M. kansasii is a slow-growing mycobacterium responsible for tuberculosis-like pulmonary diseases as well as extrapulmonary conditions such as lymphadenitis, skin, and soft tissue infections. This study aimed to determine the minimum inhibitory concentration (MIC) values of 40 M. kansasii isolates that were isolated in Turkey and to investigate mutations in the gyrA, gyrB, rpoB, rbpA, and rrl genes that are associated with drug resistance in resistant isolates. The study was conducted in five stages: conventional drug susceptibility testing, DNA extraction, amplification of gyrA, gyrB, rpoB, rbpA, and rrl genes, Sanger DNA sequencing, and next-generation sequencing. As a result of the study, all isolates were found to be susceptible to amikacin (AMK), clarithromycin (CLA), linezolid (LZD), moxifloxacin (MXF), and rifabutin (RFB); while 90% of the isolates were resistant to ciprofloxacin (CIP) and rifampin (RIF), 47.5% were resistant to doxycycline, and 70% were resistant to trimethoprim/sulfamethoxazole (TMP- SMZ). Susceptibility testing for minocycline could not be performed because minocycline is not included in the Sensititre SLOMYCO panel. Sanger sequencing revealed no mutations in the gyrA, gyrB, or rrl genes. The most frequent mutations in the Rifampin Resistance-Determining Region (RRDR) of the rpoB gene were identified at codons 447 and 457. Notably, for the first time, this study identified mutations outside the RRDR region of the rpoB gene at nucleotides 226, 617, 1191, and 2555. No mutations were detected in the rbpA gene region. This study identified novel mutations in the ropB gene, both inside and beyond the RRDR, in rifampin- resistant isolates.