Non-Tuberculous (Atypical) Mycobacteria: The Diseases, the Runyon Groups, and When to Suspect Them

A patient's sputum grows acid-fast bacilli, and the first thought is tuberculosis. But the GeneXpert is negative for M. tuberculosis, the patient is an older adult with long-standing lung disease rather than a classic TB contact, and the organism turns out to be Mycobacterium avium. This is a non-tuberculous mycobacterial infection, caused by an environmental cousin of the TB bacillus that lives in soil and water and behaves very differently.

The non-tuberculous mycobacteria (also called atypical mycobacteria) are found everywhere in the environment and usually cause disease only when the lung is already damaged or the immune system is weak. This page is about the diseases they cause, how to tell them apart from tuberculosis, and how the laboratory classifies and identifies them.

Introduction

The non-tuberculous mycobacteria (NTM) are all the mycobacteria except the M. tuberculosis complex and M. leprae. They are also called atypical mycobacteria, environmental mycobacteria, or MOTT (mycobacteria other than tubercle bacilli). They belong to the genus Mycobacterium and share its acid-fast, waxy-walled biology, covered on the Mycobacterium overview.

Three ideas explain almost everything about NTM and separate them from TB:

• They are environmental, not human-adapted. NTM live in soil, water (including tap water and shower heads), and dust. Humans catch them from the environment, not from other people, and NTM (with rare exceptions) do not spread person to person. TB, by contrast, is a human pathogen spread person to person.
• They are often opportunists. Because they are weakly pathogenic, NTM usually cause disease only when there is a breach in defenses: damaged lungs (COPD, bronchiectasis, old TB), a weakened immune system (HIV with low CD4), or a break in the skin (trauma, surgery, injection). In a healthy host they often just colonize.
• Finding one does not always mean disease. Because NTM are everywhere and can colonize without causing illness, a positive NTM culture must be interpreted with the clinical picture. This is a crucial difference from M. tuberculosis, which is essentially always significant when isolated.

How NTM differ from tuberculosis

Feature	M. tuberculosis	Non-tuberculous mycobacteria
Source	Another infected person	The environment (soil, water)
Person-to-person spread	Yes (airborne)	No (rare exceptions)
Significance when isolated	Almost always a true pathogen	May be colonization; interpret with clinical picture
Host	Anyone	Often those with damaged lungs or weak immunity
Drug susceptibility	Predictable first-line drugs	Often resistant; needs different, prolonged regimens

The practical upshot: when acid-fast bacilli are found but the picture does not fit TB (negative M. tuberculosis molecular test, an environmental exposure, a susceptible host, or a slow indolent course), think NTM, and remember that isolating one does not automatically mean it is causing disease.

The clinical syndromes: what NTM actually cause

Most NTM disease falls into four recognizable patterns. Learning these four is more useful than memorizing every species.

1. Chronic lung disease (the commonest). Resembles pulmonary TB (cough, sputum, cavities) but occurs mostly in older adults with pre-existing lung disease (COPD, bronchiectasis) or in otherwise healthy older women. Main causes: M. avium complex (MAC) and M. kansasii.

2. Cervical lymphadenitis in children. A young child develops a firm, painless, enlarging neck node that may break down and drain. In children this is more often NTM than TB. Main causes: MAC and M. scrofulaceum (the classic cause of scrofula in children).

3. Skin and soft-tissue infection after environmental exposure or trauma. Main causes: M. marinum (fish-tank / swimming-pool granuloma after contact with aquariums or water), M. ulcerans (Buruli ulcer, a destructive skin ulcer), and the rapid growers (M. fortuitum, M. chelonae, M. abscessus) after injections, surgery, tattoos, or implants.

4. Disseminated disease in the severely immunocompromised. Widespread infection, classically disseminated MAC in advanced AIDS (CD4 below 50/μL). Spreads through the blood to many organs.

A memory anchor: lungs (MAC/kansasii), neck nodes in kids (scrofulaceum/MAC), skin from water or trauma (marinum/ulcerans/rapid growers), and disseminated in AIDS (MAC).

Runyon classification: how the laboratory groups NTM

The syndromes above are clinical. In the laboratory, NTM are traditionally sorted by the older Runyon classification, based on two features: growth rate (slow vs rapid) and pigment production (and whether pigment needs light). It is being replaced by molecular identification, but it remains a useful framework and a common exam topic.

• Group I Photochromogens (pigment only in light): M. kansasii, M. marinum.
• Group II Scotochromogens (pigment in dark or light): M. scrofulaceum.
• Group III Non-chromogens (no pigment): MAC.
• Group IV Rapid growers (<7 days): M. fortuitum, M. chelonae, M. abscessus.

Group I: Photochromogens

Among the NTM classified as photochromogens, M. kansasii, M. marinum are the major potential pathogens.

Mycobacterium kansasii

Causes chronic pulmonary disease as well as infections of the skin and subcutaneous lymph nodes. The disease tends to progress slowly and is susceptible to usual mycobacterial drugs. M. kansasii causes lung disease (resembling tuberculosis). Antigenically similar to M. tuberculosis (tuberculin test positive) Susceptible to standard anti-tuberculosis drugs Environmental habitat: Tap water Geographical habitat: USA (Texas)

Mycobacterium marinum

It grows at much lower temperatures than other mycobacteria (i.e. around 30°C) and is present in both fresh and saltwater.  It causes nodular ulcerative lesions of the skin at the site of trauma. The infection can spread along the lymphatics in a sporotrichoid pattern (a line of nodules following the lymphatic drainage), typically up the arm.
Source: fresh and saltwater
Disease: Infects fish. Causes superficial granulomatous nodular skin disease of man at the site of trauma called fish-tank granuloma, also known as aquarium granuloma or swimming pool granuloma.
Treatment: Treatment uses a prolonged course of appropriate antibiotics; the specific regimen is a clinical decision.

Figure: Swimming pool granuloma caused by Mycobacterium marinum

Group II (Scotochromogens)

M. scrofulaceum is an NTM classified as scotochromogens and is found in raw milk, soil, water, and dairy products. It is the most common cause of granulomatous cervical lymphadenitis in children. The disease is characterized by enlarged lymph nodes, which may ulcerate or form draining sinus tracts.

• Natural habitat: environmental water source; human respiratory tract.
• M. scrofulaceum causes scrofula-granulomatous cervical adenitis in children.
• Enters through oropharynx and infects the draining lymph nodes
• Treatment: surgical excision of affected lymph nodes.

Group III (Non-chromogens)

Includes M. avium and M. intracellulare also referred to as M. avium-intracellulare (MAC/MAI) Complex. They are the important pathogen in immunocompromised individuals. They are found ubiquitous in the environment: water, soil, dust, animals, and poultry. Infection acquired by ingestion or inhalation.

Mycobacterium avium-intracellulare Complex (MAC)

These Non-Tuberculous Mycobacteria (NTM) are classified as Nonphotochromogens in Runyon classification. M. avium complex became a prominent human pathogen during the 1980s and 1990s with the AIDS epidemic, when disseminated MAC became a common opportunistic infection.  They are an important pathogen in immunocompromised and immunocompetent populations.

They are ubiquitous in environmental sources including natural waters; soil etc.  Taxonomically, the M. avium complex mainly comprises M. avium and M. intracellulare (together abbreviated MAC or MAI).

These organisms cause opportunistic infections in immunocompromised patients such as individuals infected with HIV. The lungs are primarily affected, but infection can spread to other organs as well. Disseminated disease is seen in the case of AIDS patients.

Disease: MAC/MAI causes opportunistic infections in immunocompromised patients. Disseminated MAC classically occurs in advanced AIDS when the CD4 count falls below 50/μL. Pulmonary disease caused by MAC is clinically indistinguishable from pulmonary tuberculosis.

Treatment is difficult. NTM are often resistant to standard anti-TB drugs and need prolonged treatment with a combination of drugs guided by the species and susceptibility. MAC lung disease, for example, is treated with a macrolide-based multidrug regimen for many months. The key teaching point is that NTM treatment is longer, uses different drugs, and is harder than TB treatment, not the specific regimen. Specific drugs, doses, and durations are clinical decisions and are not covered here.

Pathogenesis of MAC

MAC is weakly virulent. It exploits gaps in host defense rather than overwhelming a healthy person. Three features explain its behavior.

Intracellular survival in macrophages. After it is inhaled or ingested, MAC is taken up by macrophages but blocks phagosome-lysosome fusion, so it survives and multiplies inside the cell meant to kill it. This produces a slow, chronic infection and a reservoir the immune system cannot easily clear.

Lipid-rich, waxy cell wall. The mycolic-acid-rich wall protects the organism inside the macrophage and resists many antibiotics. This is a major reason MAC is intrinsically resistant to standard anti-TB drugs and needs prolonged, different treatment.

Dependence on intact cell-mediated immunity. Control of MAC depends on CD4 T cells activating macrophages. This explains the split in presentation: chronic lung disease when airways are damaged but immunity is preserved, and disseminated disease when cell-mediated immunity collapses, as in advanced AIDS with CD4 below 50/μL.

Putting it together: MAC reaches the host from water or dust → survives inside macrophages by blocking phagosome-lysosome fusion → is normally held in check by CD4 T cells. Damaged lungs allow chronic pulmonary disease. Collapsed immunity in advanced AIDS allows spread through the blood to many organs.

Mycobacterium ulcerans

Mycobacterium ulcerans causes Buruli ulcer: a necrotizing disease (causing tissue death) of the skin and underlying tissue. M. ulcerans produces a toxin called mycolactone, which destroys tissue and suppresses the local immune response and pain, so the ulcers are characteristically painless despite being large and destructive.

Buruli ulcer is the third most common mycobacterial disease worldwide after TB and leprosy. Buruli ulcer presents in two different forms

• Non-ulcerative forms are nodules, plaques and edema.
• The ulcerative form may be small or large with the typical undermined edges

Group IV: Rapid growers

Colonies appear on solid media in 7 days or less.

Mycobacterium fortuitum complex (Rapid growers)

It is a group of free-living; rapid-growing NTM. The colonies of these organisms appear on solid media in 7 days or less. They constitute the second major group of NTM. They have been found in soils, marshes, rivers etc. People acquire the infection when organisms gain entry into the host by inoculation into skin and subcutaneous trauma, injections, or surgery or through animal contact.

Injection site abscesses among drug users are the most common form of this disease but pulmonary infection occurs occasionally. Infection can also be associated with implanted devices.  Little is known about the pathogenesis of these organisms.

Of the potentially pathogenic, rapidly growing NTM, M. fortuitum, M. chelonae, and M. abscessus constitute approximately 97% of disease.

• Group of free living, rapid growing mycobacteria.
• Rarely cause human disease
• Common disease: injection-site abscesses among people who inject drugs
• Infections has also been associated with implanted devices such as heart valves, surgery and breast abscesses.

Laboratory diagnosis

NTM are acid-fast, so they look like M. tuberculosis on Ziehl-Neelsen staining, microscopy cannot tell them apart from TB. They grow on the same media (Lowenstein-Jensen, Middlebrook), and the rapid growers appear in under a week.

The real task is distinguishing NTM from M. tuberculosis and identifying the species, done by:

• Molecular methods (DNA probes, 16S rRNA sequencing, line-probe assays), now the main approach, and the reason a positive AFB result is followed by a molecular test to confirm whether it is M. tuberculosis or an NTM.
• Biochemical tests (niacin, nitrate, catalase, Tween 80 hydrolysis) and growth characteristics (rate, pigment, temperature), the traditional route, including the Runyon features above. M. tuberculosis is niacin-positive; most NTM are niacin-negative, a classic separator.

Because NTM can colonize without causing disease, the laboratory result is always interpreted alongside the clinical picture and, for lung disease, usually needs repeated positive cultures plus compatible symptoms and imaging to count as true infection.

How to remember

Environmental, opportunistic, and not contagious. The three-word summary of NTM: they come from the environment (soil, water), they strike when defenses are down (damaged lungs, weak immunity, broken skin), and they do not spread person to person. That trio separates them from TB.

Four syndromes. Lungs (MAC, M. kansasii, in damaged/older lungs), neck nodes in children (M. scrofulaceum, MAC = scrofula), skin from water or trauma (M. marinum fish-tank granuloma, M. ulcerans Buruli ulcer, rapid growers), and disseminated in advanced AIDS (MAC). Four patterns cover most NTM disease.

Runyon: Photo, Scoto, Non, Fast. Group I photochromogens make pigment in light; Group II scotochromogens make it even in the dark; Group III non-chromogens make none; Group IV are the fast (rapid) growers. Slow for I-III, fast for IV.

Finding it isn't always disease. Because NTM colonize, one positive culture may mean nothing. This is the opposite of M. tuberculosis, which always matters when isolated. Interpret NTM with the clinical picture.

Marinum likes water, ulcerans makes a painless ulcer. M. marinum = aquariums and pools (fish-tank granuloma). M. ulcerans = Buruli ulcer, painless because its mycolactone toxin numbs and destroys.

Key exam facts in one table

Fact	Detail
Definition	Mycobacteria other than M. tuberculosis complex and M. leprae
Other names	Atypical, environmental, MOTT, NTM
Source	Environment (soil, water); not person-to-person
When they cause disease	Damaged lungs, immunosuppression, skin trauma (opportunists)
Key interpretive rule	Isolation may be colonization; interpret clinically
Lung disease	MAC, M. kansasii (older adults, damaged lungs)
Childhood lymphadenitis	M. scrofulaceum, MAC (scrofula)
Skin (water/trauma)	M. marinum (fish-tank granuloma), M. ulcerans (Buruli ulcer), rapid growers
Disseminated	MAC in advanced AIDS (CD4 <50/μL)
Runyon I	Photochromogens (pigment in light): M. kansasii, M. marinum
Runyon II	Scotochromogens (pigment in dark): M. scrofulaceum
Runyon III	Non-chromogens: MAC
Runyon IV	Rapid growers (<7 days): M. fortuitum, M. chelonae, M. abscessus
Buruli ulcer toxin	Mycolactone (destructive, painless)
Niacin test	M. tuberculosis positive; most NTM negative
Treatment	Often drug-resistant; prolonged multidrug therapy; harder than TB

Where students get confused

A positive NTM culture may not mean disease. Because NTM live everywhere and colonize, isolating one is not automatically significant, unlike M. tuberculosis, which almost always matters. NTM results are interpreted with the clinical picture, often needing repeated positive cultures.

NTM are not contagious. They come from the environment, not from other people. With rare exceptions they do not spread person to person, so contact tracing and isolation (as in TB) do not apply.

They look exactly like TB on a smear. Acid-fast staining cannot separate NTM from M. tuberculosis. A positive AFB smear needs a molecular or culture-based test to say which it is. This is a frequent source of confusion when a smear is positive but TB tests are negative.

Atypical does not mean rare or harmless. "Atypical" just means "not M. tuberculosis or M. leprae." Some cause serious disease (disseminated MAC, Buruli ulcer), especially in the immunocompromised.

NTM are harder to treat than TB. They are often resistant to standard anti-TB drugs and need different, prolonged, multidrug regimens. M. kansasii is a notable exception that responds well to rifampicin-based treatment.

References

1. Bhambri, S., Bhambri, A., & Del Rosso, J. Q. (2009). Atypical mycobacterial cutaneous infections. Dermatologic Clinics, 27(1), 63–73. https://doi.org/10.1016/j.det.2008.07.009
2. Tille, P. M. (2022). Bailey & Scott's Diagnostic Microbiology (15th ed.). Elsevier.
3. Procop, G. W., et al. (2017). Koneman's Color Atlas and Textbook of Diagnostic Microbiology (7th ed.). Wolters Kluwer.
4. Daley, C. L., Iaccarino, J. M., Lange, C., et al. (2020). Treatment of nontuberculous mycobacterial pulmonary disease: An official ATS/ERS/ESCMID/IDSA clinical practice guideline. Clinical Infectious Diseases, 71(4), e1–e36. https://doi.org/10.1093/cid/ciaa241