Comparative Characteristics of Antibiotic Resistance Genes in the Fecal Microbial Community of Healthy Controls and Pulmonary Tuberculosis Patients before and after Antituberculosis Treatment

The objective: to investigate the diversity and distribution of antibiotic resistance genes within the fecal microbial community of patients with pulmonary tuberculosis (TB) compared to controls, and to analyze the impact of long-term multicomponent chemotherapy on the fecal resistome structure in TB patients.

Materials and methods. Metagenomic DNA samples obtained from fecal specimens of pulmonary TB patients and healthy individuals were used in this study. The matagenomic data analysis was performed using the microbiome R package and the Comprehensive Antibiotic Resistance Gene Annotation Database (CARD)

Results. The fecal microbial community of TB patients demonstrates high diversity of antibiotic resistance genes compared to healthy controls. TB therapy slightly reduces the diversity of resistance genes. Tetracycline resistance genes are the most abundant in the gut microbiome, followed by genes conferring resistance to lincosamides, macrolides, and aminoglycosides. The fecal microbial community of TB patients additionally harbors genes conferring resistance to fluoroquinolones, aminocoumarins, beta-lactam, and peptide antibiotics. In the healthy microbiome, the main reservoir of resistance genes is comprised of members of Bacteroidota and Bacillota phyla. In contrast, the fecal resistome of TB patients is primarily driven by genes annotated within Pseudomonadota (Escherichia, Klebsiella, Campylobacter, Citrobacter, Enterobacter, Shigella, Vibrio) and Bacillota (Staphylococcus, Streptococcus, Blautia, Lactobacillus, Eubacterium, Enterococcus). A pairwise comparison of metagenomic data of TB patients before and after chemotherapy identified four genes (pmrA, Bado_rpoB_RIF, npmA and AAC(6')-Ib7) whose abundance increased during TB treatment.

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