Mycobacteria - Part 1

Mycobacteria Overview

  • Mycobacteria include Mycobacterium tuberculosis (MTB) and other non-tuberculosis mycobacterium (NTM).

  • Around 100 recognized and proposed species under the genus Mycobacterium.

  • Strictly aerobic and intracellularly living organisms.

  • Non-spore forming except for Mycobacterium marinum which is spore forming.

  • Non motile, thin, slightly curved or straight rod-shaped organisms.

  • Extremely slow-growing: weeks necessary for noticeable growth (2-6 weeks for disease-related species).

Unique Characteristics of Mycobacteria

  • Acid-fast Cell Wall

    • Contains N-glycolyermic acid with a very high lipid content.

    • Difficult to stain with traditional methods like Gram staining.

    • Requires increased dye uptake time or the use of heat; resists decolorization with acid ethanol.

    • This trait leads to the abbreviation AFB (Acid Fast Bacilli).

Key Species of Mycobacterium

Mycobacterium tuberculosis (MTB)

  • Causative agent of tuberculosis (TB).

  • Enhanced growth in 5-10% CO2 environments; complex media required (e.g., Lohenstein Jensen agar).

  • Historical context: first described by Robert Koch in 1882; a leading cause of morbidity and mortality.

  • Estimated 1/3 of the world's population infected; 1.5 million TB-related deaths in 2014.

Mycobacterium leprae

  • Causative agent of Hansen disease (leprosy).

  • Unique inability to grow in vitro; can only be cultivated in armadillos and the footpads of mice.

Nontuberculous Mycobacterium (NTM)

  • Found in nature (soil and water); infections acquired via trauma, inhalation, or ingestion.

  • Opportunistic pathogens affecting patients with lung disease, immunosuppression, or percutaneous trauma.

  • Not transmissible person-to-person.

Runyon Classification Scheme for NTM

  • Group 1: Photochromogens

    • Very slow-growing; colonies become pigmented upon light exposure.

    • Example species: Mycobacterium cansassi, Mycobacterium marinum.

  • Group 2: Scotochromagens

    • Slow-growing; pigmented when grown both in light and dark.

    • Example species: Mycobacterium gordonae; rarely recovered.

  • Group 3: Nonphotochromogens

    • Slow-growing; no pigment production regardless of growth conditions.

    • Mostly pathogenic; includes Mycobacterium avium complex, Mycobacterium xenopi.

  • Group 4: Rapid Growers

    • Grow within 7 days on routine media; cause infections primarily from post-traumatic wounds.

    • Example species: Mycobacterium fortuitum, Mycobacterium chelonae.

Pathology of Mycobacterium tuberculosis

  • Mode of transmission: inhalation of droplets from person-to-person.

  • Infection typically occurs in the alveoli of the lungs.

  • Once in the body, phagocytized by immune cells and multiplies within them.

  • Immunological response occurs 4-6 weeks post-infection, led by T cells; may form granulomas that can remain dormant.

Risk Factors for Reactivation of TB

  • Individuals with HIV are more susceptible to TB.

  • Reactivation risk factors include advanced age, immunosuppression (AIDS, drugs), malnutrition, alcoholism, and incarceration.

Symptoms of Tuberculosis

  • In children: nonproductive cough, potentially with shortness of breath.

  • In adults: can develop into progressive pulmonary TB.

  • Positive tuberculin skin test indicates prior exposure; uses purified protein derivatives of MTB.

  • Skin test outcomes:

    • 5-9 mm: category 1 positive

    • 10-14 mm: category 2 positive

    • >15 mm: category 3 positive.

Stages of Tuberculosis

  1. Primary Active Tuberculosis

    • Can lead to disseminated TB via lymphatic spread.

    • Common in patients with ineffective cellular immunity.

  2. Latent Tuberculosis

    • No apparent signs or symptoms; not infectious.

    • Can reactivate under weakened immunity conditions.

  3. Reactivation of Tuberculosis

    • Occurs in situations where cellular immunity is compromised.

    • Symptoms include fever, night sweats, chills, fatigue, and weight loss.

Complications of Tuberculosis

  • Potential complications due to delayed diagnosis/treatment:

    • Emphysema

    • Pleural fibrosis

    • Massive hemoptysis

    • Adrenal insufficiency

    • Drug-resistant TB.

Characteristics of Mycobacterium tuberculosis Colonies

  • Slow-growing with a raised, dry, and rough appearance.

  • Lack pigmentation; may be buff-colored.

  • Presence of cord factor, leading to cell arrangements resembling long slender formations, crucial for virulence and survival in hosts.

Biochemical Tests for Mycobacterium tuberculosis Identification

  • Niacin test: positive

  • Ability to reduce nitrates to nitrites is observed.

Treatment of Tuberculosis

  • First-line agents: isoniazid and rifampin.

  • Possible addition of streptomycin or ethambutol for a 2-8 week course.

  • Pyrazinamide used if cellular immunity is compromised.

  • Other options include kanamycin or ciprofloxacin.

Treatment Considerations

  • Treatment failure potential due to:

    • Inappropriate antimicrobial use

    • Patient noncompliance

    • Drug-resistant mycobacteria acquisition.

  • Resistance often arises from using single drugs; emphasizes the need for combination therapy.

Mycobacterium avium Complex

  • A slow-growing species commonly found in the environment (soil, water, particularly coastal marshes).

  • Most common non-tuberculosis mycobacterium in the U.S.; primarily seen in immunocompromised patients.

  • Can also affect swine, cattle, and poultry.

Symptoms and Characteristics

  • Particularly affects middle-aged men with smoking history and pre-existing lung disease.

  • Increased isolation of Mycobacterium avium due to HIV/AIDS demographics.

  • Colonies: very slow-growing, thin with a non-pigmented transparent or opaque appearance.

  • Microscopic appearance: short, coccobacillary, uniformly stained without banding.

Treatment of Mycobacterium avium Complex

  • Surgical excision combined with chemotherapy for localized non-pulmonary disease.

  • Note: Mycobacterium avium complex shows partial resistance to TB drugs; necessitates higher drug concentrations and combination therapies.

Mycobacterium cansassi

  • Most are photochromogens; carotene pigment produced with light exposure.

  • Second most common cause of non-tuberculous lung disease in the U.S.

  • Causes chronic pulmonary lung disease, primarily affecting the upper lobes without scarring.

  • Colonies on Lohenstein Jensen agar: smooth to rough texture, wavy edges, and dark centers.

  • Microscopic observation: long rods with distinct cross banding.