Mycobacterium and E.Coli Notes

Mycobacterium

  • A group of bacteria; some are harmless, some cause disease.

Basic Features

  • Aerobic: Needs oxygen to live

  • Non-motile: Doesn't move on its own

  • Non-spore-forming: Doesn't make survival spores

  • Rod-shaped: Looks like a stick

  • Acid-fast: Has a thick wall that holds stain

Types of Mycobacteria

M. tuberculosis Complex (causes TB)
  • Species:

    • M. tuberculosis: Main cause of TB in people

    • M. bovis: TB in cows, can infect humans; infects cattle + humans

    • M. africanum: Less common, in Africa; infects humans

M. avium Complex (MAC)
  • A group of related bacteria that can cause disease in birds, humans, pigs, and other animals.

  • Often found in the environment (soil, water).

  • Subspecies:

    • M. avium ssp. avium: Affects birds; causes a TB-like disease in birds; lives in soil/water, usually harmless

    • M. avium ssp. hominissuis: Affects humans and swine; infects people (especially with weak immune systems) and pigs

    • M. avium ssp. paratuberculosis: Affects ruminants (e.g., cows, sheep); Causes Johne's disease – a chronic gut disease in ruminants

Environmental
  • Lives in soil/water, usually harmless- Can cause disease if your immunity is weak

Summary Table

  • Pathogenic: Always causes disease

    • M. tuberculosis Complex

      • Species: M. tuberculosis, M. bovis, M. africanum

      • Host(s) Affected: Humans, cattle, other mammals

      • Type of Infection: Tuberculosis (TB)

    • M. avium Complex (MAC)

      • Species: M. avium ssp. avium, hominissuis, paratuberculosis

      • Host(s) Affected: Birds, humans, pigs, ruminants

      • Type of Infection: TB-like or gut diseases

  • Environmental

    • Species: Various Mycobacteria

    • Host(s) Affected: Rarely cause disease, Can infect weak immune systems

Pathogenic Mycobacteria

  • M. tuberculosis

    • Main Hosts: Man, captive primates

    • Species Occasionally Infected: Dogs, cattle, psittacine birds, canaries

    • Disease: Tuberculosis (worldwide)

  • M. bovis

    • Main Hosts: Cattle

    • Species Occasionally Infected: Deer, badgers, possums, man, cats, other mammalian species

    • Disease: Tuberculosis

  • M. africanum

    • Main Hosts: Man

    • Disease: Tuberculosis (regions in Africa)

  • M. avium complexa

    • Main Hosts: Most avian species except psittacines

    • Species Occasionally Infected: Pigs, cattle

    • Disease: Tuberculosis

  • M. microti

    • Main Hosts: Voles

    • Species Occasionally Infected: Other mammalian species

    • Disease: Tuberculosis

  • M. marinum

    • Main Hosts: Fish

    • Species Occasionally Infected: Man, aquatic mammals, amphibians

    • Disease: Tuberculosis

  • M. leprae

    • Main Hosts: Man

    • Species Occasionally Infected: Armadillos, chimpanzees

    • Disease: Leprosy

  • M. lepraemurium

    • Main Hosts: Rats, mice

    • Species Occasionally Infected: Cats

    • Disease: Rat leprosy, feline leprosy

  • M. avium subsp. paratuberculosis

    • Main Hosts: Cattle, sheep, goats, deer

    • Species Occasionally Infected: Other ruminants

    • Disease: Paratuberculosis (Johne's disease)

Morphological characteristics

Acid-fast
  • They don't lose color after acid staining because of their thick, waxy cell wall.

    • Cell wall has a lot of lipids (fats)

    • These lipids make it hard for stains to enter.

    • So, heat is needed during staining to force the dye into the cell.

Shape and Arrangement
  • Where it's found

    • In tissues (inside the body)

      • Appears alone, in pairs, or in small groups

    • On artificial media (like lab plates)

      • Shape varies by species

Appearance/Arrangement
  • Mycobacterium tuberculosis

    • In clinical samples: looks like a bundle of faggots (tied sticks)

    • Often forms serpentine cords (twisted ropes)

  • Mycobacterium avium

    • Rod-shaped (straight or slightly curved)

    • Can appear coccoid (round) or filamentous (long threads)

    • More coccoid (round-shaped)

  • Not all look the same; it depends on the exact type of Mycobacterium

Extra Traits (All Mycobacteria)
  • Non-motile: They don't move on their own

  • No spores: They don't make spores for survival

  • No capsule: They don't have a protective capsule around them

Resistance

Resistance to Physical Conditions
  • Can survive in soil and dried feces for months

    • Even when dried out, they stay infectious.

    • This makes them dangerous in environments where hygiene is poor.

  • Not resistant to heat

    • 60°C60°C kills them in 15-20 minutes.

    • So, boiling or high heat can be used to sterilize.

Survival in Sputum (Mucus from Lungs)
  • Wet sputum: Survives for 20-30 hours so they can infect others if coughed out

  • Dried sputum: Survives up to 4 years, extremely long survival if left on surfaces. That's why TB can spread through shared surfaces, especially if not cleaned properly. Quick wiping doesn't work. You need to let it sit to be effective.

  • Dry soil or feces: Survives for months

  • Heat (60°C60°C): Killed in 15-20 min

  • Sunlight (direct, 2 hours): Killed

  • Wet sputum: Survives 20-30 hours

  • Dried sputum: Survives up to 4 years

Resistance to Chemical Disinfectants
  • Some strong chemicals do not kill Mycobacteria easily. Chemical Are They Killed?

    • 5% Phenol: No (resistant)

    • 15% Sulfuric acid (H<em>2SO</em>4H<em>2SO</em>4): No (resistant)

    • 3% Nitric acid: No (resistant)

    • 5% Oxalic acid: No (resistant)

    • 4% Sodium hydroxide (NaOH): No (resistant)

  • These acids and bases would kill many bacteria, but Mycobacteria can survive them.

  • Direct sunlight kills lab cultures in 2 hours

    • Sunlight (UV rays) damages their DNA, killing them.

What Actually Kills Them?
  • Some disinfectants are effective, but timing matters. Disinfectant Time Needed to Kill

    • Tincture of iodine 5 minutes- Works well on skin and surfaces

    • 80% Ethanol (alcohol) 2 to 10 minutes- Alcohol must be left for enough time. But this applies to exposed bacteria, not those protected in mucus or dirt.

  • Disinfectants (phenol, acids): Resistant

  • Iodine (tincture): Killed in 5 minutes

  • Ethanol (80%): Killed in 2-10 minutes

Virulence Factors

  • Virulence appears to reside in the lipids of the cell wall.

  • Cell wall of the Mycobacterium is composed of peptidoglycan, arabinogalactan and mycolic acid.

  • Outer layer of the cell wall - lipids, mycosides. (Peptidoglycolipids or phenolic glycolipids).

  • Mycosides - responsible for the control of cellular permeability, resistance to action of water-soluble enzymes, antibiotics and disinfectants.

  • Sulfatides - sulfur containing glycolipids -inhibits phagolysosome formation and avoid exposure to hydrolytic enzymes present in the lysozomes.

  • Mycosides, phospholipids and sulpholipids are protecting the tubercle bacilli against Phagocytosis.

Pathogenesis

How TB Enters the Body (Transmission)
  • Tuberculosis is caused by Mycobacterium tuberculosis, and it enters the body in two main ways:

  • Inhalation (main route):

    • When a person with active TB coughs, sneezes, or speaks, they release droplets containing the bacteria.

    • A healthy person breathes in those droplets. The bacteria travel deep into their lungs.

  • Ingestion (less common):

    • Happens by drinking unpasteurized milk from infected cows (with M. bovis).

    • This was more common before milk pasteurization was introduced.

Attachment and Entry into the Lungs
  • Once inhaled, the bacteria:

    • Attach to dust or droplet particles.

    • Travel to the alveolar spaces - the smallest air sacs in the lungs, where oxygen is exchanged.

  • Here, the bacteria are picked up by macrophages, a type of white blood cell that usually destroys microbes.

Spread Within the Body
  • After multiplying in the lungs:

  • Infected macrophages carry the bacteria to nearby lymph nodes.

  • From there, bacteria enter the thoracic duct, which drains into the bloodstream.

  • This leads to systemic spread - the bacteria can now reach many organs (like the liver, spleen, brain, kidneys, and bones).

  • This stage is known as primary tuberculosis.

Delayed Immune Response (After 10-14 Days)
  • The immune system doesn't react immediately.

  • It takes 10-14 days for a cell-mediated immune (CMI) response to begin.

  • This involves:

    • T-cells recognizing the infected cells

    • Macrophages becoming activated and starting to kill some of the bacteria

  • Not all bacteria are killed.

  • The body tries to contain the infection rather than fully eliminate it.

Tubercle Formation (Granuloma)
  • As the immune system tries to control the infection:

    • Macrophages cluster around the infected area in the lung tissue.

    • The body creates a fibrous capsule around this cluster to wall it off.

  • This structure is called a tubercle or granuloma.

  • Inside the tubercle:

    • Some macrophages become specialized giant cells.

    • The center begins to break down due to cell death and forms a cheese-like material.

Caseous Necrosis (Tissue Breakdown)
  • This stage is marked by:

    • Destruction of infected tissue inside the tubercle.

    • The center becomes soft, yellowish, and crumbly - called caseous necrosis (meaning "cheese-like death").

  • Later:

    • This material may calcify (harden and form scar tissue).

    • Or liquefy and lead to cavity formation in the lung.

    • These cavities are full of bacteria and can spread infection when the person coughs.

Summary Table: Tuberculosis Pathogenesis
  • Transmission Inhaled droplets (main route); also through infected milk

  • Entry site Alveolar spaces in the lungs

  • Initial response Macrophages take in bacteria but can't kill them

  • Spread Via lymph nodes à thoracic duct à bloodstream (systemic infection)

  • Immune response Starts after 10-14 days; T-cells and macrophages attempt to control spread

  • Granuloma (tubercle) Cluster of immune cells forms around infection; surrounded by fibrous wall

  • Caseous necrosis Center of tubercle dies and forms soft, cheese-like tissue

  • Possible outcomes Fibrosis (healing), calcification, or liquefaction leads to active TB

Diagnosis of tuberculosis

  • Microscopical examination.

  • X-ray

  • Intra dermal caudal fold tuberculin test.

  • Cultures morphology, growth characteristics in media, biochemical characteristics.

  • Histopathology.

  • ELISA.

  • Polymerase chain amplification (PCR).

  • Whole-blood gamma interferon (IFN-) assay.

  • Animal pathogenicity in guinea pigs, rabbits and chicken.

Treatment and control

TB Treatment in Humans
  • Streptomycin was the first effective antibiotic used for TB. It was introduced in the 1940s and helped reduce TB deaths for the first time.

Modern Treatment
  • TB is now treated with two or more antibiotics at the same time to:

    • Kill the bacteria more effectively

    • Prevent resistance

Common TB Drugs Used Together:
  • Antibiotic Name Function

    • Rifampin Stops the bacteria from making proteins

    • Isoniazid Blocks the production of cell walls

    • Ethambutol Weakens the cell wall

    • TB treatment usually lasts 6 months or longer.

Control of Bovine TB (in Cattle)
  • TB in cattle is caused by M. bovis and can spread to humans. So controlling it is important.

Testing and Slaughter (Main Method)
  • Tuberculin test is used to detect infected cattle. If a cow tests positive, it is slaughtered to prevent the spread. Despite this, bovine TB is not yet fully eradicated.

Depopulation of Herds
  • If an entire herd is infected or at high risk, all animals are removed (depopulated).This prevents the infection from spreading to other farms.

Disinfection of Premises
  • After removing animals, the environment must be cleaned. Effective disinfectants include:

    • Cresylic compounds

    • Sodium orthophenylphenate

    • Strong chemical cleanersUsed to clean animal areas

BCG Vaccine in Cattle
  • BCG = Bacillus Calmette-Guérin vaccine. It is used in humans in some countries. NOT used in cattle control programs because:

    • It makes tuberculin testing unreliable (can give false positives).

    • It is illegal in the EU.

    • No international program currently accepts BCG use for cows.

Summary Table
  • First human TB treatment:

    • Streptomycin, 1940s

  • Common antibiotics:

    • Rifampin, Isoniazid, Ethambutol (used together)

  • Bovine TB testing:

    • Tuberculin test + slaughter

  • Herd control:

    • Depopulate heavily infected herds

  • Disinfection:

    • Use cresylic compounds or sodium orthophenylphenate

  • Cattle vaccine:

    • BCG not used, illegal in the EU, not part of any global program

Paratuberculosis

Paratuberculosis (Johne's Disease)

Cause of the Disease
  • Caused by: Mycobacterium avium subspecies paratuberculosis (MAP)

  • It's a chronic and irreversible disease - meaning it develops slowly and cannot be cured once it sets in.

Who It Affects

Animal Type Notes
* Cattle Most commonly affected
* Sheep and Goats Also very susceptible
* Camels Can be infected
* Wild Ruminants Includes deer, antelope, etc.
* These are all ruminants, meaning animals that chew cud and have a multi-chambered stomach.

What the Disease Does
  • Causes severe weight loss ("wasting") over time.The animal eats but keeps losing weight.

  • Diarrhea may also occur in some species (like cattle).

  • Eventually leads to death or early culling.

Transmission (How it Spreads)
  • Mainly affects young animals - they get infected early in life.

  • How they get it: by eating food or water contaminated with feces from infected animals.

  • MAP bacteria are shed in feces, even before the animal shows symptoms.

Survival in the Environment
  • MAP can stay alive in the environment for up to one year.

  • This happens if conditions are suitable (moisture, shade, organic material).

  • This makes controlling the disease very difficult on farms.

Possible Link to Human Disease
  • There is uncertainty (no clear proof yet) about whether MAP causes Crohn's disease in humans.

  • Crohn's disease is a chronic intestinal inflammation in people.

  • Some researchers believe there may be a connection, but it is still debated.

Key Details
  • Causative Agent:

    • Mycobacterium avium ssp. paratuberculosis (MAP)

  • Disease Name:

    • Johne's disease / Paratuberculosis

  • Affects:

    • Cattle, sheep, goats, camels, wild ruminants

  • Symptoms:

    • Weight loss, chronic infection, no recovery

  • Spread:

    • Young animals ingest MAP from infected feces

  • Environmental survival:

    • Up to 1 year under suitable conditions

  • Link to human disease:

    • Possible connection to Crohn's disease, still under investigation

Pathogenesis and Pathogenicity

Incubation Period
  • The incubation period (time between infection and visible signs) is:

    • Very long

    • Varies from animal to animal

  • Animals can be infected for months or years before showing any symptoms.

Not All Animals Show Symptoms
  • Some animals:

    • Never develop visible disease

    • Are called subclinical carriers

  • These carriers can still shed the bacteria in their feces now and then.

  • This spreads infection silently in the herd.

How Infection Starts in the Body
  • The bacteria (MAP) enter the animal through the mouth.

  • They go to the intestine and are:

    • Engulfed by macrophages (immune cells that usually kill bacteria)

    • But MAP survives inside these cells and starts to multiply.

  • The first place they go is the Peyer's patches, which are lymphoid tissues in the small intestine (especially in young animals).

Progression of Disease
  • Over time, the body responds with inflammation.

  • A granulomatous reaction happens - this is when:

    • Immune cells (especially lymphocytes and macrophages) build up in the gut walls.

  • This thickens the tissue, especially in the lamina propria and submucosa (layers of the intestine).

Effect on the Body (Enteropathy)
  • The damaged gut causes enteropathy, which means intestinal disease.

  • This leads to:

    • Loss of plasma proteins (important body proteins leaking into the gut)

    • Poor absorption of:

      • Nutrients

      • Water

  • The animal eats normally but still loses weight and energy and may get diarrhea

Table - Stage/Concept & Description
  • Incubation Period

    • Long and varies; can be months or years

  • Subclinical Carriers

    • Infected animals that show no signs but shed bacteria in feces

  • Entry Point

    • Bacteria enter through the mouth and are taken in by macrophages

  • First Site of Infection

    • Peyer's patches in the small intestine

  • Immune Response

    • Granulomatous inflammation with buildup of lymphocytes and macrophages

  • Damaged Tissues

    • Lamina propria and submucosa (intestinal wall layers)

  • Results

    • Protein loss, poor nutrient and water absorption

Pathogenesis and pathogenicity (Expanded)

Immune Reactions and Their Effects

Different immune responses cause different symptoms in infected animals:
Immune Response Type What It Does Resulting Symptoms
* Immediate hypersensitivity Quick allergic-like response: Diarrhea
* Delayed hypersensitivity Slower immune reaction over time: Emaciation (severe weight loss) and anemia (low red blood cells)
* Failure of protein synthesis Body can't make enough proteins: Muscle atrophy (muscle wasting)
* Cytotoxic effect Immune cells kill infected cells: More muscle atrophy and kidney (renal) damage

When Do Clinical Signs Appear?
  • Most ruminants don't show symptoms at first.

  • They go through a long subclinical phase - they're infected but look healthy.

  • Symptoms develop later, sometimes years after infection.

Signs in Cattle
  • Usually appear in animals older than 2 years.

  • First signs:

    • Intermittent diarrhea (comes and goes)

  • Later:

    • Diarrhea becomes profuse and constant

    • Weight loss continues even if appetite is normal

Visible Damage to Organs (Found on Post-mortem or Endoscopy)
  • Affected Area | What Happens

    • Terminal small intestine and large intestine | Inner lining (mucosa) becomes thickened and forms transverse folds (corrugations)

    • Mesenteric and ileocaecal lymph nodes | These lymph nodes become swollen (enlarged) and filled with fluid (oedematous)

Summary Table
  • Immediate hypersensitivity Causes diarrhea

  • Delayed hypersensitivity Causes weight loss and anemia

  • Failed protein synthesis Leads to muscle wasting

  • Cytotoxic effects Damage to muscles and kidneys

  • Onset of symptoms After a long subclinical phase

  • In cattle Signs after 2 years: starts with intermittent diarrhea, becomes constant

  • Intestinal changes Mucosa becomes thick, folded

  • Lymph node changes Swollen and fluid-filled (oedematous)

Control

Control of Paratuberculosis

Goal of Control
  • The main goal is to reduce how often the disease appears in a herd.

  • Control methods don't eliminate the bacteria completely but help lower the number of infected animals over time.

Vaccine Use and Restrictions
  • Vaccines are available in some countries, but they have limitations:

    • Vaccinated animals often react to tuberculin tests, just like TB-infected animals would.

    • This causes problems in areas where tuberculosis testing is important.

    • Because of this, the use of vaccines is regulated (restricted or banned) in some countries to avoid false TB test results.

Key Husbandry Practices (Farm Management)

Practice Why It's Important
* Screen new animals before buying Prevents bringing in infected animals
* Separate newborns (neonates) Stops them from getting infected by mothers or adult animals
* Use clean birthing areas Birth (parturition) should happen in non-contaminated spaces, Protects young animals from adult carriers Prevents early-life exposure to MAP
* Don't feed raw colostrum/milk Infected milk or colostrum can transmit the disease to young animals , Avoids oral transmission of bacteria

Cleaning and Disinfection
  • Farm environments must be cleaned regularly, especially areas exposed to manure or birthing materials.

  • Sodium orthophenylphenate is a disinfectant used to clean surfaces, pens, and equipment. It helps kill MAP bacteria that might survive in the environment.

Additional Control Methods

Isolate Sick Animals Immediately

Animals showing clinical signs of Johne's disease (e.g. weight loss, diarrhea) must be isolated from the rest of the herd or flock.
Isolating them helps protect healthy animals from getting infected.

Detecting and Eliminating Subclinical Animals (Silent Carriers)

Subclinical animals are infected but show no symptoms and still shed bacteria, usually in small amounts.

Subclinical Animal Testing

Testing should be done for whole herds or flocks

Regular testing methods
  • Faecal culture (every 6 months): Identifies hidden shedders (slow but reliable)

  • DNA probe tests (e.g. PCR): Fast detection of MAP DNA in feces

  • Serological testing (Absorbed ELISA): Detects antibodies in blood from subclinical animals

  • Regular testing helps find and remove silent shedders before they infect others.

Vaccination in Calves (Live Vaccine)
  • A live vaccine is available in some places.It uses a nonpathogenic strain of Mycobacterium avium ssp. paratuberculosis.

  • Given subcutaneously (under the skin) to calves before they are 4 weeks old, the goal is to protect young animals before exposure to contaminated environments.

E.coli

Gram-negative bacteria properties
  • Gram negative- LPS

  • O-antigen

  • Capsule
    *M-antigen -protection against dessication(drying)
    *K-antigen is a serum resistance, disinfectant resistant, mucosal adherence properties

Adhesins

*Commensals of intertinal tract.
*Resistance
1)Not sunlight, posterization, drying, disinfectant resistant
2)Need moist shaded environment

Pathogenesis

*Transmission
*Inhalation
*Ingestion

Virulence
  • Responsible for cell permeability

  • Bacteria enters via dust and water into aveolar spaces