Exploration of the relationship between Sigma factor gene expression and isoniazid resistance in Mycobacterium tuberculosis.

Objective To investigate whether the expression regulation of regulatory gene Sigma factors (sigA-sigM) is related to isoniazid resistance phenotype in isoniazid-resistant Mycobacterium tuberculosis (MTB) caused by katG mutations, and to provide reference for the study of the molecular mechanism of isoniazid resistance. Methods A total of 90 strains were collected from the patients undergoing first-line treatment at the Tianjin Tuberculosis Control Center during drug resistance testing from 2020 to 2022, of which 30 strains were sensitive strains without katG mutation, and 65 strains were isoniazidresistant strains caused by katG mutation, including 11 strains resistant only to isoniazid, 24 strains resistant to both isoniazid and streptomycin, and 30 strains multidrug-resistant to isoniazid, streptomycin, and rifampicin. After the strains were collected on the isoniazid drug-containing medium, the RNA of the strains was extracted, and the relative expression levels of Sigma factors were detected by reverse transcription-polymerase chain reaction(RT-PCR). The expression differences of Sigma factors in different isoniazid drug-resistant phenotypes were analyzed by the Mann-Whitney U test. Results The gene expression levels of sigA, sigC, sigF, sigG, sigH, sigI, sigJ, sigK, sigL in isoniazid mono-resistant group were significantly higher than those in pan-isoniazid-sensitive group (Z=4.368, 5.701, 6.865, 4.021, 5.126, 2.670, 5.983, 4.701, 5.490, P all<0.001). The gene expression levels of sigA, sigC, sigF, sigG, sigH, sigI, sigJ, sigK, sigL in poly-resistance group were significantly higher than those in pan-sensitivity group (Z=-5.017, -4.670, -4.667, -5.456, -4.083, -5.393, -4.712, -6.971, -8.206, -5.211, P all< 0.001). In multidrug-resistant (MDR) group, the gene expression levels of sigC, sigD, sigE, sigF, sigG, sigH, sigI, sigJ, sigK, sigL were significantly higher than those in pan-isoniazid-sensitive group (Z=-5.537, -4.003, -5.216, -7.328, -7.730, - 5.658, -4.440, -6.036, -4.862, -4.312, P all<0.001). The expression levels of sigB, sigF, sigG showed statistically significant differences in gene expression between the isoniazid mono-resistant, isoniazid poly-resistant, and isoniazid multidrug-resistant groups (Z=10.139, 7.735, 14.532, P all<0.001). The expression rates of sigF, sigG, sigI, sigJ, and sigL in the isoniazid-resistant group were significantly higher than those in isoniazid sensitive group (χ²=17.410. 45.673. 57.661. 42.896. 26.363, P all< 0.001). Conclusions sigF, sigG, sigI, sigJ, and sigL are associated with isoniazid resistance due to katG mutations. [ABSTRACT FROM AUTHOR]