Single-nucleotide polymorphisms related to fluoroquinolone and aminoglycoside resistance in mycobacterium avium isolates

Abstract

The relationships between fluoroquinolone and aminoglycoside resistance and single-nucleotide polymorphisms (SNPs) in gyrA, gyrB, and rpsL genes were investigated in 95 clinical isolates of Mycobacterium avium from China. Methods: Fluoroquinolone and aminoglycoside resistance were determined by the broth microdilution method. GyrA, gyrB, and rpsL were sequenced, SNPs were identified, and the corresponding amino acid mutations were recorded. Results: The M. avium isolates displayed high levels of ofloxacin (93.68%), ciprofloxacin (92.63%), and streptomycin (65.26%) resistance. Moxifloxacin (18.95%) and amikacin (2.11%) were highly active against the strains. Fluoroquinolone resistance involving gyrA and gyrB gene mutations was identified. For gyrA, the most frequent SNPs were T→C (71/95, 74.74%), followed by A→G (64/95, 67.37%) and T→C (62/95, 65.26%). The amino acid mutations occurred mainly at Gly2444Asp (GGT→GAT) (20/95, 21.05%), Ala2445Ser (GCC→TCC) (20/95, 21.05%), Ala2447Val (GCC→GTC) (20/95, 21.05%), Val2449Ile (GTC→ATC) (20/95, 21.05%), and Glu2450Gln (GAA→CAA) (20/95, 21.05%). Prominent SNPs in gyrB included A→C (69/95, 72.63%), C→T (51/95, 53.68%), and T→G (29/95, 30.53%), and their amino acid substitutions were Ile2160Val (ATT→GTT) (21/95, 22.11%), Ile2160Met (ATT→ATG) (20/95, 21.05%), and Ile2273Leu (ATC→CTC) (11/95, 11.58%). Among the strains with aminoglycoside resistance, SNPs in rpsL were identified mostly at position G→A (73/95, 76.84%). G→C (21/95, 22.11%) was commonly seen. The amino acid mutations primarily involved Ala1539985Thr (GCC→ACC) (19/95, 20.00%), His1539992Asp (CAC→GAC) (19/95, 20.00%), and Gln- 1539983Glu (CAG→GAG) (18/95, 18.95%). Conclusion: Our study provides valuable information that could be used for the future diagnosis and treatment of M. avium disease.