PMC9487995_01
Treatment history, CT images, phylogenetics and drug resistance profiles, and unfixed mutation subgroups of drug resistance genes. (A) Treatment History. Anti-tuberculosis drugs used in different periods. (B) Three-dimensional visualization of CT scans demonstrates the longitudinal anatomical change in lung lesions. Lesions in different lung lobes are shown in different colors, and the trachea (blue) and pulmonary contours (light gray) are shown as references. There were two independent cavities 1 (red) and 2 (green) in the right upper lobe parenchymal abnormality (dark gray) in March 2017, which appeared partial absorption in September 2019, and subsequently fused extensively and infiltrated outward (magenta) from March to July 2021. Such rapid deterioration resulted in the destruction of the right upper lung lobe. All other lung lobar lesions showed a benign response to treatment or remained relatively stable. Lesions of the right middle lobe (cyan), right lower. lobe (yellow), left upper lobe (pink), and left lower lobe (orange) are also shown in the (B). (C) Whole-genome sequencing. Five strains belong to L2. Mutations that confer drug resistance are shown. FLUOROQUINOLONES (gyrA), RIFAMPICIN (rpoB), STREPTOMYCIN (rpsL), AMIKACIN (rrs), LINEZOLID (rrl), ISONIAZID (fabG1_promoter, katG), PYRAZINAMIDE (pncA), ETHAMBUTOL (embB). (D) Unfixed mutation subgroups of drug resistance genes. Resistance to amikacin developed in 2021. Percentages on the y axis are based on the number of genome-sequencing reads supporting the corresponding drug resistance-conferring mutation.
fpubh-10-966891-g0001.jpg
PMC9487995_01_fpubh-10-966891-g0001.jpg
F1
The fusion lesion infiltrated outward and deteriorated rapidly, resulting in the destruction of the entire right upper lobe (Figures 1A,B, Table 1). Given that drug selection pressure is the primary driver of resistance mutations in strains, and no EMB and PZA related mutations were found in cluster 2, we speculate that cluster 1 was the first infected strain of this patient (Figures 1C,D).