# From anonymity to stardom: history of nontuberculous mycobacterial disease in humans

**Authors:** Surendra Kumar Sharma, Vishwanath Upadhyay, Alladi Mohan

PMC · DOI: 10.3389/fcimb.2025.1717909 · Frontiers in Cellular and Infection Microbiology · 2026-02-23

## TL;DR

This paper reviews the history and evolution of nontuberculous mycobacterial disease in humans, focusing on advances in diagnosis and treatment.

## Contribution

The paper provides a comprehensive historical and contemporary analysis of NTM disease management and classification.

## Key findings

- Over 200 NTM species have been identified due to improved diagnostic methods.
- Molecular tests now enable rapid and accurate NTM diagnosis.
- Treatment decisions depend on clinical relevance and species-specific regimens.

## Abstract

Until recently, nontuberculous mycobacteria (NTM) were not considered as human pathogens. Their nomenclature has evolved over several years, until 1971 when finally named as NTM, which is universally accepted now. Because of continuously evolving diagnostic methods, several new species/subspecies of NTM were identified. Presently, nearly 200 NTM species have been reported. Similar to tuberculosis (TB), NTM are known to involve both pulmonary and extrapulmonary organs. Diagnosis of NTM disease is quite cumbersome and is primarily based on their growth characteristics on solid and liquid cultures. Biochemical testing was the mainstay of NTM diagnosis and species identification in the past, which was often erroneous. Recently, molecular tests like line probe assay, targeted, and whole genome sequencing have become available for rapid and accurate diagnosis. Isolation and identification of NTM species/subspecies alone do not warrant treatment. After ascertaining clinical relevance, virulence of NTM species, and evidence for clinical and radiological progression, the decision to administer treatment is taken. Multiple drugs are often administered for 12 months after sputum culture conversion, except in M. kansasii, and M. szulgai, where this constitutes the total treatment duration, with careful follow‑up for relapse and exogenous new infection. The present review traces the history, evolution of classification of NTM, strides made in the diagnosis and treatment of NTM disease. By integrating these historical lessons on taxonomy, culture phenotypes, genotypes and diagnostic pitfalls with contemporary molecular tools and species/subspecies specific treatment regimens, current practice enables more precise, timely, and patient−centered management of NTM disease.

## Linked entities

- **Diseases:** tuberculosis (MONDO:0018076)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, SQSTM1 (sequestosome 1) [NCBI Gene 8878] {aka A170, DMRV, EBIAP, FTDALS3, NADGP, OSIL}, HBD (hypophosphatemic bone disease) [NCBI Gene 100187828], CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820] {aka CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26}, IFNGR1 (interferon gamma receptor 1) [NCBI Gene 3459] {aka CD119, IFNGR, IMD27A, IMD27B}, HBA2 (hemoglobin subunit alpha 2) [NCBI Gene 3040] {aka ECYT7, HBA-T2, HBH}, HBA1 (hemoglobin subunit alpha 1) [NCBI Gene 3039] {aka ECYT7, HBA-T3, HBH, METHBA}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TMT1B (thiol methyltransferase 1B) [NCBI Gene 196410] {aka ALDI, METTL7B}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, NBR1 (NBR1 autophagy cargo receptor) [NCBI Gene 4077] {aka 1A1-3B, IAI3B, M17S2, MIG19}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, TFEB (transcription factor EB) [NCBI Gene 7942] {aka ALPHATFEB, BHLHE35, TCFEB}, IKBKG (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma) [NCBI Gene 8517] {aka AMCBX1, EDAID1, FIP-3, FIP3, Fip3p, IKK-gamma}, HBD (hemoglobin subunit delta) [NCBI Gene 3045] {aka HBK}, IL31RA (interleukin 31 receptor A) [NCBI Gene 133396] {aka CRL, CRL3, GLM-R, GLMR, GPL, IL-31RA}, IL12RB1 (interleukin 12 receptor subunit beta 1) [NCBI Gene 3594] {aka CD212, IL-12R-BETA1, IL12RB, IMD30}, IRF8 (interferon regulatory factor 8) [NCBI Gene 3394] {aka H-ICSBP, ICSBP, ICSBP1, IMD32A, IMD32B, IRF-8}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, LAMP1 (lysosome associated membrane protein 1) [NCBI Gene 3916] {aka CD107a, LAMPA, LGP120}, OPTN (optineurin) [NCBI Gene 10133] {aka ALS12, FIP2, GLC1E, HIP7, HYPL, NRP}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, CYBB (cytochrome b-245 beta chain) [NCBI Gene 1536] {aka AMCBX2, CGD, CGDX, GP91-1, GP91-PHOX, GP91PHOX}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IFNGR2 (interferon gamma receptor 2) [NCBI Gene 3460] {aka AF-1, IFGR2, IFNGT1, IMD28}, ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636] {aka G1P2, IFI15, IMD38, IP17, UCRP, hUCRP}, MIR484 (microRNA 484) [NCBI Gene 619553] {aka MIRN484, hsa-mir-484, mir-484}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}
- **Diseases:** inborn errors (MESH:D008661), musculoskeletal and prosthetic infections (MESH:D009140), M. avium Complex (MESH:C566367), bacterial infections (MESH:D001424), acid (MESH:D011015), RGM (MESH:C538458), fibrotic granulomas (MESH:D006099), MOTT (MESH:D014376), HIV (MESH:D015658), Buruli ulcer (MESH:D054312), necrosis (MESH:D009336), chronic (MESH:D002908), Infectious Diseases (MESH:D003141), silicosis (MESH:D012829), chronic infection (MESH:D000088562), Gut-lung axis (MESH:C566610), leprosy (MESH:D007918), death (MESH:D003643), neutrophil-predominant (MESH:C564275), bronchiectasis (MESH:D001987), pulmonary TB (MESH:D014397), infection (MESH:D007239), toxicity (MESH:D064420), latent TB infection (MESH:D055985), AIDS (MESH:D000163), cutaneous granulomatous disease (MESH:D006105), MAC-PD (MESH:D048090), ALIS (MESH:D015208), airway injury (MESH:D000402), inborn (MESH:D030342), HIV/AIDS (MESH:D016263), GATA2 (MESH:D000077428), lymphadenitis (MESH:D008199), trauma (MESH:D014947), skin and soft tissue infection (MESH:D018461), inflammation (MESH:D007249), abscesses (MESH:D000038), fibrosis (MESH:D005355), granulomatous (MESH:D013968), Respiratory Disease (MESH:D012140), MDR (MESH:D018088), X-linked defects (MESH:C538116), NTM- (MESH:D009165), acquired (MESH:D003638), PD (MESH:D008171), Cancer (MESH:D009369), opportunistic infection (MESH:D009894), CF (MESH:D003550), extra-pulmonary NTM disease (MESH:D000092225), mycobacterial disease (MESH:C564468)
- **Chemicals:** amiodarone (MESH:D000638), 2,2,4,6,6-pentamethyl-heptane (MESH:C469781), ATP (MESH:D000255), lipopeptide (MESH:D055666), lipids (MESH:D008055), mycolactone (MESH:C117218), RNS (MESH:D011886), tridecane (MESH:C094074), trehalose (MESH:D014199), ROS (MESH:D017382), D-phenylalanine (-), 6-deoxytalose (MESH:C011754), para-amino salicylic acid (MESH:D010131), amino-alcohol (MESH:D000605), oligosaccharide (MESH:D009844), cystine (MESH:D003553), reactive nitrogen species (MESH:D026361), macrolide (MESH:D018942), amikacin (MESH:D000583), rifabutin (MESH:D017828), metformin (MESH:D008687), rufomycins (MESH:C000633644), iron (MESH:D007501), acetylcholine (MESH:D000109), glycolipids (MESH:D006017), resveratrol (MESH:D000077185), clofazimine (MESH:D002991), ethanol (MESH:D000431), omadacycline (MESH:C000591640), methionine (MESH:D008715), Cefoxitin (MESH:D002440), adenosine (MESH:D000241), PAS (MESH:D011478), alaninol (MESH:C034448), pyrazinamide (MESH:D011718), acid (MESH:D000143), hypoxanthine (MESH:D019271), pyrazinoic acid (MESH:C005296), mycolic acid (MESH:D009171)
- **Species:** Cavia porcellus (domestic guinea pig, species) [taxon 10141], Gallus gallus (bantam, species) [taxon 9031], Mycobacterium gordonae (species) [taxon 1778], Mycobacteroides chelonae (species) [taxon 1774], Mycobacteroides abscessus (species) [taxon 36809], Mycobacterium avium (species) [taxon 1764], Mycobacterium intracellulare (species) [taxon 1767], Mycobacterium kansasii (species) [taxon 1768], Human immunodeficiency virus (species) [taxon 12721], Mycobacterium scrofulaceum (species) [taxon 1783], Mycobacterium marinum (species) [taxon 1781], Mycobacterium haemophilum (species) [taxon 29311], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Mycobacterium tuberculosis (species) [taxon 1773], Segatella copri (species) [taxon 165179], Homo sapiens (human, species) [taxon 9606], Mycolicibacterium fortuitum (species) [taxon 1766], Mycobacterium tuberculosis complex (species group) [taxon 77643], Cheloniidae (sea turtles, family) [taxon 8465], Human immunodeficiency virus 1 (no rank) [taxon 11676], Mycobacterium leprae (species) [taxon 1769], Mycobacteriales (order) [taxon 85007], Mycolicibacterium smegmatis (species) [taxon 1772], Mycobacterium ulcerans (species) [taxon 1809], Mycobacterium malmoense (species) [taxon 1780], Mus musculus (house mouse, species) [taxon 10090], Mycobacterium xenopi (species) [taxon 1789], Oscillospira sp. F (species) [taxon 227390], Mycobacterium avium complex sp. (species) [taxon 37162]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12968181/full.md

## References

156 references — full list in the complete paper: https://tomesphere.com/paper/PMC12968181/full.md

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Source: https://tomesphere.com/paper/PMC12968181