Week of 10/28-Amoebas: Organism Description and Disease

Amoebas: Organism Description and Disease

Basic Organism Description

  • Single-celled anaerobic eukaryote

  • Free-living and parasitic

  • No definitive shape: Constantly changing form

  • Pseudopodia:

    • Means of locomotion and feeding

    • Considered most primitive form of animal locomotion

Detailed Organism Description

  • Cell Structure:

    • Single nucleus

    • Cytoplasm divided into two parts:

    • Ectoplasm

    • Endoplasm:

      • Contains food vacuoles

      • Granular nucleus

      • Contractile vacuole (absent in many parasitic species)

  • Feeding Mechanism:

    • No mouth or anus; food obtained through phagocytosis

  • Mitochondria:

    • Lacks mitochondria but has mitosome: a mitochondrion-related organelle

  • Energy Production:

    • Does not produce ATP

    • Possibly involved in sulfate activation, producing sulfolipids that aid in cell growth

  • Oxygen Diffusion:

    • Occurs with surrounding water

  • Survival Mechanism:

    • Can survive harsh environmental conditions by encystment:

    • Loses most water contents

    • Becomes circular

    • Creates a cyst membrane

    • Will re-emerge when environmental conditions improve

Life Cycle - General

  • Divided into two main stages:

    1. Trophozoites

    • Feeding and dividing form

    • Feed mainly on bacteria

    • Size: approximately 10 – 20 microns

    • Uninucleated

    • Divide by binary fission to become cysts via encystation

    1. Cysts

    • Transmission stage

    • Can have 1, 4, or 8 nuclei depending on species

Amoebas and Disease

  • Prevalence:

    • About 10% of the world’s population has Entamoeba in their digestive tract

    • Most are asymptomatic due to infection with Entamoeba dispar (a non-parasitic amoeba)

    • Globally, ~50 million people contract infection each year

    • Results in over 100,000 deaths annually, making it the leading parasitic cause of death

  • Transmission:

    • Usually spread through fecal-oral transmission

    • Can also spread through water/mucous membranes

  • Virulence Factors:

    • Virulent strains over-express genes that code for:

    • Lysine-rich factors

    • Glutamic-rich and lysine-rich proteins

    • Function of these genes is not well known

Susceptibility to Amoebic Diseases

  • General Susceptibility:

    • Anyone can be susceptible; however, certain groups/conditions increase risk:

    • Individuals living in poor sanitary conditions

    • Institutionalized individuals

    • Young individuals often present a more severe form of the disease

  • Other Risk Factors:

    • Use of corticosteroids

    • Poor nutrition

    • Pregnancy

    • Toxic megacolon

    • Alcohol use

    • Cancer

Entamoeba histolytica

  • Disease Cause:

    • Causes amoebic dysentery

  • Life Cycle:

    1. Cysts ingested by host

    • Cysts have a cell wall made of chitin, which is highly resistant to environmental conditions

    1. Once ingested, cysts travel to the small intestine, emerge as trophozoites

    2. Trophozoites are swept down to the large intestine where they multiply in lumen by binary fission

    • May either become encysted or invade gut wall/bloodstream

    1. If encysted, will be expelled via feces; one person can pass over 10 million cysts per day

Consequences of Entamoeba histolytica Infection

  • Invasion:

    • Trophozoites can attack and ingest epithelial cells lining the gut wall

    • Spread through underlying layers, creating flask-shaped ulcers from irritation

    • Leads to widespread bleeding in the intestine

  • Complications:

    • Secondary bacterial infections may arise, resulting from healing ulcers that create scar tissue

    • Decreased gut elasticity leads to loss of functional surface

    • Compromised water re-absorption in large intestine results in loose stools containing mucous and blood

    • Possible development of:

    • Proctocolitis

    • Toxic megacolon

    • Peritonitis

    • Brain abscess

    • Pericarditis

Acanthamoeba

  • First Identification:

    • Identified as a possible disease-causing agent during polio vaccine development in 1958

  • Environmental Presence:

    • Commonly found in lakes, swimming pools, tap water, air conditioning units, dialysis units, vegetables, and dental treatment units

    • Among the most prevalent protozoa, distributed worldwide

  • Life Cycle:

    • Similar to Entamoeba histolytica with trophozoite and cyst stages

    • Can act as a bacterial reservoir (bacteria can infect and replicate within the parasite)

  • Distinguishing Feature:

    • Trophozoite form has “spines” (acanthopodia)

Consequences of Acanthamoeba Infection

  • Main Complications:

    1. Keratitis:

    • Risk factors include improper contact lens cleaning

    • Estimated 1-2 new cases per 1 million contact lens users in the US each year

    1. Encephalitis:

    • High fatality, estimated at 97%

    • Death occurs within weeks to months

    • Risk factors include:

      • Individuals who are immunocompromised

      • Diabetes

      • Malignancies

      • Malnutrition

      • Lupus

      • Steroid treatment

      • Chemotherapy

      • Alcoholism

Acanthamoebic Keratitis

  • Description:

    • Infection occurs in the eye, leading to corneal ulcers and potential blindness

  • Symptoms Include:

    • Eye pain

    • Eye redness

    • Blurred vision

    • Excessive tearing

    • Feeling of something in the eye

    • Light sensitivity

Acanthamoebic Encephalitis

  • Pathophysiology:

    • Parasite enters the bloodstream and crosses the blood-brain barrier

    • Can enter through lungs, nasal passages, or skin lesions

    • Causes proinflammatory responses leading to neuronal damage, severe necrosis, and edema

  • Symptoms Include:

    • Headaches

    • Altered mental status

    • Seizures

    • Stiff neck

    • Fever

    • Coma

    • May be mistaken for bacterial meningitis

Balamuthia mandrillaris

  • Discovery:

    • First discovered in 1986, found in the brain of a mandrill

  • Characteristics:

    • Free-living amoeba, opportunistic parasite

    • Found in multiple mammals (including dogs, primates, and horses)

    • Commonly found in dust, soil, and water

  • Life Cycle:

    • Involves trophozoite and cyst stages

    • Spread by contact with wounds, cuts, or inhalation through lungs

    • Incubation can range from weeks to years

    • Once inside, parasitic lodges in skin and brain, ingesting host tissue using tissue-degrading enzymes

    • Immune response results in necrosis, granuloma, hemorrhage, and lesions

Consequences of Balamuthia mandrillaris Infection

  • Causes: Amebic Encephalitis

  • Symptoms Include:

    • Fever

    • Headache

    • Vomiting

    • Lethargy

    • Nausea

    • Seizures

    • Weakness

    • Confusion

    • Partial paralysis

  • Rarity:

    • Only about 200 cases have been reported since 1990

    • Often results in fatal outcomes

    • Associated with significant brain pathology, leading to edema, hemorrhage, and meningoencephalitis

Naegleria fowleri

  • Type: Free-living amoeba, opportunistic parasite

  • Life Cycle:

    1. Trophozoite (reproductive stage)

    2. Cyst

    3. Flagellate: Occurs in low food source environments when trophozoite becomes flagellate

    • Will revert back to trophozoite form

  • Pathophysiology:

    • Attaches to nasal mucosa and travels through olfactory nerves to olfactory bulbs

    • Elicits an intense immune response

    • Trophozoite food cups ingest tissue and release cytolytic molecules that contribute to host cell and nerve degeneration

Consequences of Naegleria fowleri Infection

  • Causes: Primary amebic meningoencephalitis

  • Estimated Cases: 1-8 cases per year in the US

  • Symptoms Include:

    • Stage 1:

    • Severe frontal headache

    • Fever

    • Nausea

    • Vomiting

    • Stage 2:

    • Stiff neck

    • Seizures

    • Altered mental status

    • Coma

  • Fatality: Almost always fatal

  • Potential Environments:

    • Found in warm fresh water, geothermal water (hot springs), warm water discharge from industrial plants, poorly maintained swimming facilities, tap water, soil, and sediment in water bodies.

Basic Organism Description
  • Single-celled anaerobic eukaryote: Typically classified under Amoebozoa, characterized by pseudopodial movement and often anaerobic or microaerophilic metabolism.

  • Free-living and parasitic: Can exist independently in various environments or as pathogens within hosts.

  • No definitive shape: Constantly changing form as it moves and feeds.

  • Pseudopodia: Plasma membrane projections vital for:

    • Locomotion: Extending forward and pulling the cell body along.

    • Feeding: Engulfing food particles through phagocytosis.

    • Considered the most primitive form of animal locomotion.

Detailed Organism Description
  • Cell Structure:-

    • Single nucleus: Contains the genetic material.

    • Cytoplasm divided into two parts:

      • Ectoplasm: The outer, clear, gel-like layer involved in cell movement.

      • Endoplasm: The inner, more fluid, granular layer containing organelles.

        • Contains food vacuoles (phagosomes) where digestion occurs.

        • Granular nucleus often centrally located.

        • Contractile vacuole: Regulates osmotic pressure (absent in many parasitic species like Entamoeba).

  • Feeding Mechanism: No mouth (cytostome) or anus (cytoproct); food obtained through phagocytosis, where the plasma membrane invaginates to engulf particles, forming a food vacuole.

  • Mitochondria: While many pathogenic amoebas lack classical mitochondria, they possess mitosomes: relict mitochondrion-related organelles that do not perform oxidative phosphorylation. These mitosomes are conserved in some anaerobic eukaryotes.

  • Energy Production: Primarily relies on glycolysis for ATP production, which is characteristic of anaerobic or microaerophilic metabolism.

    • Mitosomes are possibly involved in iron-sulfur cluster biogenesis and sulfate activation, producing sulfolipids that are important for cell growth and survival.

  • Oxygen Diffusion: Occurs passively with surrounding water, indicating its reliance on low oxygen or anaerobic environments.

  • Survival Mechanism: Can survive harsh environmental conditions by encystment (forming a cyst):

    • Loses most water contents: Facilitates metabolic dormancy.

    • Becomes circular: Reduces surface area.

    • Creates a multi-layered cyst wall: Offers significant protection against dessication, chemicals, and temperature extremes.

    • Will re-emerge as a trophozoite when environmental conditions improve (excystation).

Life Cycle - General
  • Divided into two main stages:

    1. Trophozoites

      • The active, feeding, and dividing form responsible for disease manifestations.

      • Feeds mainly on bacteria, host cells, and cellular debris.

      • Size: approximately 10 – 60 microns for many pathogenic species, but can vary.

      • Typically uninucleated in feeding stage.

      • Divides by binary fission to increase numbers and can transform into cysts via encystation under unfavorable conditions.

    2. Cysts

      • The dormant, non-feeding, and environmentally resistant transmission stage.

      • Protected by a thick cell wall.

      • Can have 1, 4, or 8 nuclei depending on the species, which is a key diagnostic feature.

Amoebas and Disease
  • Prevalence: About 10%10\% of the world’s population carries Entamoeba in their digestive tract.

    • Most are asymptomatic due to infection with non-pathogenic species like Entamoeba dispar or Entamoeba moshkovskii.

    • Globally, approximately 5050 million people contract symptomatic amoebic infection each year, primarily from Entamoeba histolytica.

    • Results in over 100,000100,000 deaths annually, making it the leading parasitic cause of death after malaria.

  • Transmission: Usually spread through fecal-oral transmission from contaminated food or water, or direct person-to-person contact.

    • Can also spread through contaminated water or contact with mucous membranes.

  • Virulence Factors: Virulent strains, particularly Entamoeba histolytica, over-express genes coding for key factors that enable tissue invasion and evasion of host defenses:

    • Gal/GalNAc lectin: A surface adhesin crucial for binding to host cells, including colonic mucin and epithelial cells.

    • Amoebapores: Pore-forming peptides that insert into target cell membranes, leading to cell lysis.

    • Cysteine peptidases (proteases): Enzymes that degrade extracellular matrix proteins, complement components, and host tissue, facilitating invasion and immune evasion.

    • Lysine-rich factors and Glutamic-rich and lysine-rich proteins: Their precise function is still under active investigation, but they are associated with more virulent phenotypes.

Entamoeba histolytica
  • Disease Cause: The causative agent of amoebic dysentery (intestinal amoebiasis) and extraintestinal amoebiasis, most commonly amoebic liver abscess (ALA).

  • Life Cycle:1. Cysts ingested by host:
    - Transmission occurs when infectious quadrinucleated cysts are ingested, typically via contaminated food or water.
    - Cysts have a cell wall primarily made of chitin, which confers high resistance to gastric acids and environmental conditions.

    1. Once ingested, cysts travel to the small intestine, where they undergo excystation to release motile trophozoites.

    2. Trophozoites are swept down to the large intestine (colon), where they multiply in the lumen by binary fission and can colonize the mucosal surface.

      • Trophozoites may either become encysted (forming new cysts) and be expelled via feces, or invade the gut wall and potentially the bloodstream to cause extraintestinal disease.

    3. If encysted, they are expelled via feces; an infected person can pass over 1010 million cysts per day, contributing to widespread transmission.

Consequences of Entamoeba histolytica Infection
  • Invasion: Trophozoites utilize their virulence factors (e.g., Gal/GalNAc lectin, amoebapores, cysteine peptidases) to attack and ingest epithelial cells lining the gut wall.

    • They spread through the underlying submucosa, creating characteristic flask-shaped ulcers due to localized necrosis and inflammation.

    • This invasive process leads to widespread tissue destruction, inflammation, and bleeding in the intestine, manifesting as bloody diarrhea.

  • Complications:-

    • Secondary bacterial infections may arise in damaged tissues, complicating healing and potentially leading to abscess formation.

    • Healing ulcers can result in scar tissue, leading to decreased gut elasticity and loss of functional surface area.

    • Compromised water re-absorption in the large intestine results in frequent, loose stools containing mucous and blood (dysentery).

    • Possible development of severe complications:

      • Proctocolitis: Inflammation of the rectum and colon.

      • Toxic megacolon: Rapid dilation of the colon with systemic toxicity.

      • Peritonitis: Inflammation of the peritoneum if the gut wall perforates.

      • Amoebic Liver Abscess (ALA): The most common extraintestinal manifestation, occurring when trophozoites reach the liver via the portal vein.

      • Less commonly, brain abscess or pericarditis can occur, often with severe outcomes.

Acanthamoeba
  • First Identification: Identified as a possible disease-causing agent during polio vaccine development in 1958, when it was isolated from contaminated cell cultures.

  • Environmental Presence: Ubiquitous in nature, commonly found in lakes, swimming pools, hot tubs, tap water, distilled water systems, air conditioning units, dialysis units, vegetables, and dental treatment units.

    • Among the most prevalent protozoa, distributed worldwide in soil and water.

  • Life Cycle: Similar to Entamoeba histolytica with environmentally resistant cyst and active trophozoite stages.

    • Uniquely, Acanthamoeba can act as a bacterial reservoir; various bacteria (e.g., Legionella pneumophila, Mycobacterium avium) can infect and replicate within the amoeba, using it as a protective host.

  • Distinguishing Feature: The trophozoite form is characterized by numerous, spine-like pseudopodia called acanthopodia, which aid in locomotion and feeding.

Consequences of Acanthamoeba Infection
  • Main Complications:1. Acanthamoeba Keratitis (AK): - A painful, progressive infection of the cornea, leading to corneal ulcers, stromal infiltrates, and severe pain. - Risk factors prominently include improper contact lens care, such as using tap water or homemade solutions for cleaning/storing lenses, or swimming with lenses. - Estimated 11 - 22 new cases per 11 million contact lens users in the US each year, affecting soft contact lens wearers disproportionately.

    1. Granulomatous Amoebic Encephalitis (GAE):

      • A rare but highly fatal infection of the central nervous system, typically affecting immunocompromised individuals.

      • High fatality, estimated at 97%97\%, with death often occurring within weeks to months of symptom onset.

      • Risk factors include: Individuals who are immunocompromised (e.g., HIV/AIDS), diabetes, malignancies, malnutrition, lupus, prolonged steroid treatment, chemotherapy, and alcoholism.

Acanthamoebic Keratitis
  • Description: An ocular infection where Acanthamoeba trophozoites and cysts invade the corneal stroma, causing inflammation and tissue damage. If untreated, it can lead to severe vision loss or blindness, often requiring corneal transplant.

  • Symptoms Include: Progressive and often disproportionately severe eye pain, marked eye redness, blurred vision, excessive tearing, feeling of a foreign body in the eye, and pronounced light sensitivity (photophobia). A characteristic "ring infiltrate" may be observed in the cornea.

Acanthamoebic Encephalitis (GAE)
  • Pathophysiology: The parasite enters the bloodstream, typically through the respiratory tract, disrupted skin, or potentially the eyes, and subsequently crosses the blood-brain barrier to infect the brain.

    • Can enter through lungs, nasal passages, or skin lesions.

    • Its presence causes widespread proinflammatory responses, granuloma formation, and severe neuronal damage, necrosis, and edema in brain tissue.

  • Symptoms Include: Progressive headaches, altered mental status (confusion, disorientation), seizures, stiff neck (meningismus), persistent fever, coma, and focal neurological deficits.

    • May be mistaken for bacterial meningitis or viral encephalitis due to overlapping symptoms, leading to diagnostic delays.

Balamuthia mandrillaris
  • Discovery: First discovered in 1986 in a mandrill baboon brain during post-mortem examination, recognized as a new species in 1993.

  • Characteristics: A free-living amoeba, an opportunistic pathogen capable of causing severe disease.

    • Found in multiple mammals (including dogs, primates, and horses) and humans.

    • Commonly found in dust, soil, and water environments worldwide.

  • Life Cycle: Involves both trophozoite and cyst stages, similar to Acanthamoeba.

    • Exposure typically occurs via contact with soil-contaminated wounds, skin cuts, or inhalation of cysts/trophozoites through aerosols in the lungs.

    • Incubation period is highly variable, ranging from weeks to years.

    • Once inside the host, the amoeba can lodge in the skin (cutaneous lesions) and primarily the brain, where it ingests host tissue using potent tissue-degrading enzymes.

    • The host immune response results in necrosis, granuloma formation, hemorrhage, and chronic inflammatory lesions, leading to severe neuropathology.

Consequences of Balamuthia mandrillaris Infection
  • Causes: Primarily causes Granulomatous Amoebic Encephalitis (GAE), similar to Acanthamoeba, but can also present with skin lesions (cutaneous amoebiasis) that may precede CNS involvement.

  • Symptoms Include: A prolonged and insidious onset, including fever, persistent headache, vomiting, lethargy, nausea, seizures, weakness, confusion, and partial paralysis. Skin lesions, if present, can be atypical.

  • Rarity: Only about 200200 cases have been reported worldwide since 1990, but it is likely underdiagnosed.

    • It almost always results in fatal outcomes, making it one of the most lethal parasitic infections.

    • Associated with significant brain pathology, leading to severe edema, widespread hemorrhage, and chronic meningoencephalitis.

Naegleria fowleri
  • Type: A thermophilic, free-living amoeba and an opportunistic parasite, famously known as the "brain-eating amoeba."

  • Life Cycle: Uniquely exists in three forms:

    1. Trophozoite: The active, reproductive stage (amoeboid form), responsible for causing disease.

    2. Cyst: A dormant, environmentally resistant stage that allows survival in adverse conditions.

    3. Flagellate: A temporary, pear-shaped, biflagellated form that occurs in low food source environments or dilute water, allowing for rapid movement.

      • The flagellate form can revert back to the trophozoite form when conditions become favorable (e.g., presence of food, higher temperature).

  • Pathophysiology: Infection occurs when contaminated warm freshwater is forced up the nasal passages.

    • The trophozoites attach to the nasal mucosa and rapidly travel along the olfactory nerves through the cribriform plate to the olfactory bulbs of the brain.

    • It elicits an intense inflammatory immune response in the brain, leading to rapid tissue destruction.

    • Trophozoites use specialized food cups (amoebastomes) to ingest host brain tissue and release cytolytic molecules (e.g., phospholipases) that contribute to rapid host cell lysis and nerve degeneration.

Consequences of Naegleria fowleri Infection
  • Causes: Primary Amebic Meningoencephalitis (PAM), an acute, fulminant, and rapidly fatal infection of the central nervous system.

  • Estimated Cases: Rare, with approximately 11 - 88 cases per year in the US, predominantly in southern states during summer months.

  • Symptoms Include:-

    • Stage 1 (typically 11 - 77 days post-infection): Abrupt onset of severe frontal headache, high fever, nausea, and vomiting.

    • Stage 2 (progressing rapidly within days): Encephalitis symptoms intensify, including stiff neck, seizures, altered mental status (confusion, hallucinations), coma, and often leads to death.

  • Fatality: Almost always fatal, with a mortality rate exceeding 97%97\%, usually within 55 - 77 days of symptom onset.

  • Potential Environments: Found predominantly in warm fresh water bodies (lakes, rivers, ponds, canals), geothermal water (hot springs), warm water discharge from industrial plants, poorly maintained swimming facilities without adequate chlorination, tap water (rarely, if untreated), soil, and sediment in water bodies. It does not survive in saltwater.