Dae Hun Kim

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection primarily caused by Mycobacterium avium complex (MAC) and Mycobacterium abscessus. These species differ markedly in antibiotic susceptibility and treatment response, yet the contribution of the respiratory microbiome to this clinical variability remains unclear. To date, however, comparative analyses of microbiome differences between MAC-PD and M. abscessus-PD and their associations with disease severity are limited. Methods: We conducted microbiome analysis of sputum from 37 patients with NTM-PD. Patients were antibiotic-naïve and classified into MAC-PD (n = 29) and M. abscessus-PD (n = 8) groups. Disease severity was determined using radiologic extent on chest computed tomography. Bacterial communities were profiled by 16S rRNA gene sequencing, and differential taxa and predicted functional pathways were analyzed using LEfSe and KEGG orthology databases. Results: Distinct microbiome profiles were observed between MAC-PD and M. abscessus-PD. Three anaerobic species—Porphyromonas pasteri, Fusobacterium periodonticum, and Prevotella nanceiensis—were significantly enriched in M. abscessus-PD (LDA effect size > 3, p < 0.05). Functional biomarker analysis revealed significant enrichment of the cobalamin (vitamin B12) biosynthesis pathway in patients with severe disease, while the C19/C18 steroid hormone biosynthesis pathway was enriched in those with mild disease (p < 0.05). Conclusions: In conclusion, our study demonstrates distinct differences in the respiratory microbiome between MAC-PD and M. abscessus-PD and identifies specific functional pathways associated with disease severity in NTM-PD. These findings highlight the potential value of microbial metabolic signatures as biomarkers for disease assessment.

Dae Hun Kim, Ph.D.*, Sungmin Zo, M.D.*, Su-Young Kim, Ph.D., and Byung Woo Jhun, M.D., Ph.D.. Ann Lab Med 2024;44:92-6. https://doi.org/10.3343/alm.2024.44.1.92

Background: The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome of disease-invaded lesions and non-invaded lung tissue from NTM-PD patients. Methods: We analyzed lung tissues from 23 NTM-PD patients who underwent surgical lung resection. Lung tissues were collected in pairs from each patient, with one sample from a disease-involved site and the other from a non-involved site. Lung tissue microbiome libraries were constructed using 16S rRNA gene sequences (V3–V4 regions). Results: Sixteen (70%) patients had Mycobacterium avium complex (MAC)-PD, and the remaining seven (30%) had Mycobacterium abscessus-PD. Compared to non-involved sites, involved sites showed greater species richness (ACE, Chao1, and Jackknife analyses, all p = 0.001); greater diversity on the Shannon index (p = 0.007); and genus-level differences (Jensen-Shannon, PERMANOVA p = 0.001). Analysis of taxonomic biomarkers using linear discriminant analysis (LDA) effect sizes (LEfSe) demonstrated that several genera, including Limnohabitans, Rahnella, Lachnospira, Flavobacterium, Megamonas, Gaiella, Subdoligranulum, Rheinheimera, Dorea, Collinsella, and Phascolarctobacterium, had significantly greater abundance in involved sites (LDA >3.00, p Acinetobacter had significantly greater abundance at non-involved sites (LDA = 4.27, pM. abscessus-PD (n = 7), and between nodular bronchiectatic form (n = 12) and fibrocavitary form (n = 11) patients. However, there was no genus with a significant q-value. Conclusions: We identified differential microbial distributions between disease-invaded and normal lung tissues from NTM-PD patients, and microbial diversity was significantly higher in disease-invaded tissues. Trial registration: Clinical Trial registration number: NCT00970801.

Limited data are available regarding the in vitro activity of clofazimine against nontuberculous mycobacteria (NTM) or on outcomes of clofazimine-containing regimens in NTM-pulmonary disease (PD). Therefore, we evaluated the in vitro activity of clofazimine and the clinical outcomes of clofazimine-containing regimens. We evaluated clofazimine in vitro activity for 303 NTM isolates from NTM-PD patients. Fifty-seven clarithromycin-resistant and 35 amikacin-resistant isolates were also analyzed. Culture conversion after a 12-month treatment regimen containing clofazimine was evaluated in 58 NTM-PD patients, including 20 patients with drug-resistant isolates. Most of the 303 isolates (238/303) had minimum inhibitory concentrations (MICs) ≤ 0.25 µg/mL for clofazimine (57/63 Mycobacterium avium, 53/57 M. intracellulare, 49/52 M. kansasii, 22/64 M. abscessus, and 57/67 M. massiliense). For the 57 clarithromycin-resistant and 35 amikacin-resistant isolates, most had MICs ≤ 0.25 µg/mL (47/57 and 32/35, respectively). Among the 38 NTM-PD patients without resistance to clarithromycin or amikacin, 47% achieved culture conversion (8/27 M. abscessus, 9/9 M. massiliense, 0/1 M. avium, and 1/1 M. intracellulare). The conversion rate was higher in the MIC ≤ 0.25 µg/mL group than in the MIC = 0.5 µg/mL group (13/18 vs. 5/20, p = 0.004), and an MIC ≤ 0.25 µg/mL remained a significant factor in multivariable analysis. Culture conversion was achieved in 20% of 20 patients with clarithromycin- or amikacin-resistant isolates. However, a clofazimine MIC ≤ 0.25 µg/mL was not significant for culture conversion in the 58 NTM-PD patients, regardless of the drug resistance pattern. Clofazimine was effective in vitro against NTM species. Some patients on clofazimine-containing regimens achieved culture conversion.

The absorption spectra and input photon-to-converted current efficiency curves showed that Au nanoparticles increased the plasmonic broadband light absorption, thereby enhancing the short-circuit current density of the inverted organic photovoltaic (OPV) cells with a Au–ZnO nanocomposite electron transport layer (ETL). The power conversion efficiency of the inverted OPV cell fabricated with a Au–ZnO nanocomposite ETL was higher by 40% than that of the inverted OPV cell fabricated with a ZnO nanoparticle ETL, which could be attributed to the enhanced photon absorption in the active layer due to the localized surface plasmonic resonance of the Au nanoparticles.