Ann Clin Microbiol 2025;28(3):18. Challenges and advances in mycobacterial molecular typing
| Mycobacterium tuberculosis | Nontuberculous mycobacteria | |
|---|---|---|
| Infection source | Human-to-human transmission via aerosols | Environmental reservoirs: water, soil, biofilm, medical equipment |
| Transmission dynamics | High person-to-person spread, clustered outbreaks | Rare human-to-human transmission, pseudo-outbreaks often due to laboratory/medical contamination |
| Genotyping purpose | Transmission tracking, antimicrobial resistance, outbreak investigation Examples: A WGS study by Walker et al. [14] revealed that a presumed outbreak cluster in London identified by MIRU-VNTR included unrelated strains, prompting refined definitions for transmission. | Species identification, relapse vs. re-infection, source tracking Examples: A WGS study by Bryant et al. [15] identified direct patient-to-patient transmission of M. abscessus among patients with CF, revising the assumption that NTM are exclusively environmental. |
| Clinical manifestation | Pulmonary and extrapulmonary TB; granulomatous inflammation | Chronic pulmonary infection in bronchiectasis/CF, lymphadenitis, disseminated disease in immunocompromised patients |
| Resistance prediction | Correlates with known resistance mutations (rpoB, katG, inhA, gyrA/B) | More variable and species dependent, fewer validated resistance markers |
| Standardization | Well-developed platforms (SITVIT, ReSeqTB, TB Portals), WHO guidelines | Absence of centralized genomic databases, fragmented implementation of surveillance activities, limited WGS pipelines for routine use |
| Main genotyping tools | Spoligotyping, MIRU-VNTR, WGS, SNP-based clustering | hsp65/rpoB sequencing, MLST, WGS, gene markers |
| SNP threshold for relatedness | ≤ 12 SNPs for recent transmission (standardized) | Undefined, varies by species (ranges <10–500 SNPs), no gold standard cutoff |
| Implication of findings | Guides contact tracing, resistance treatment, public health response | Informs clinical management, environmental control, re-infection risk stratification |
Abbreviations: WGS, whole-genome sequencing; MIRU-VNTR, mycobacterial interspersed repetitive unit–variable number tandem repeat; CF, cystic fibrosis; NTM, nontuberculous mycobacteria; TB, tuberculosis; WHO, World Health Organization; SNP, single nucleotide polymorphism; MLST, multilocus sequence typing.