Free-living Acanthamoeba species are commonly found in lakes, swimming pools, tap water, and heating and air conditioning units. Several Acanthamoeba species are implicated in human disease, including A. astronyxis, A. culbertsoni, A. polyphaga, A. castellanii, A. hatchetti, A. rhysodes, A. divionensis, A. lugdunensis, and A. lenticulata (as discussed by Kong , however, many aspects of species-level Acanthamoeba taxonomy are not yet resolved). These are opportunistic free-living amebae capable of causing granulomatous amebic encephalitis (GAE), an extremely serious disease of the central nervous system, in individuals with compromised immune systems, as well as amebic keratitis, a painful eye disease that can result in blindness. Although Acanthamoeba infections are infrequent, they appear to occur worldwide (Centers for Disease Control Parasites and Health website; Marciano-Cabral and Cabral 2003 and references therein; Schuster and Visvesvara 2004 and references therein)
Acanthamoeba species are among the most prevalent protozoans in the environment. They have been found, among other locations, in soil; fresh, brackish, and sea water; sewage; swimming pools; contact lens equipment; medicinal pools; dental treatment units; dialysis machines; heating, ventilating, and air conditioning systems; mammalian cell cultures; vegetables; human nostrils and throats; and human and animal brain, skin, and lung tissues. In the laboratory, they have been isolated from emergency eye wash stations, where they pose a danger to persons with a damaged cornea (Schuster and Visvesvara 2004). In contrast to Naegleria fowleri, an amoeba that causes rare but extremely dangerous infections, Acanthamoeba life cycles have only two stages, a dormant cyst stage and an actively feeding and dividing trophozoite stage (Acanthamoeba have no flagellated stage). The trophozoites replicate by mitosis (the nuclear membrane does not remain intact). Although the trophozoites are the infective stage, both cysts and trophozoites gain entry into the body through various means. Entry can occur through the eye, the nasal passages to the lower respiratory tract, or ulcerated or broken skin. When Acanthamoeba enter the eye, severe keratitis can result in otherwise healthy individuals, particularly contact lens users (Ibrahim et al. 2007). When they enter the respiratory system or through the skin, they can invade the central nervous system by hematogenous dissemination, causing granulomatous amebic encephalitis (GAE) or disseminated disease, or skin lesions in individuals with compromised immune systems. Acanthamoeba cysts and trophozoites are found in tissue. (Centers for Disease Control Parasites and Health website; Marciano-Cabral and Cabral 2003 and references therein)
Marciano-Cabral and Cabral (2003), Schuster and Visvesvara (2004), Khan (2006), and Visvesvara et al. (2007) reviewed the biology of Acanthamoeba and the role of these organisms as human pathogens. Thomas et al. (2010) reviewed the role of free-living amoebae, particularly Acanthamoeba species, in facilitating infection of humans by various other microrganisms, as well as strategies for controlling free-living amoebae in the environment (e.g., in water supplies). Khan (2008) reviewed medical aspects of Acanthamoeba infection in humans, with a focus on understanding how these parasites manage to invade the central nervous system.
Description of Acanthamoeba
Acanthamoeba is a genus of amoebae, one of the most common protozoa in soil, and frequently found in fresh water and other habitats. The cells are small, usually 15 to 35 μm in length and oval to triangular in shape when moving. Acanthamoeba is able to form metabolically inactive cysts which are resistant to fluctuations in temperature and pH levels. Cysts are also resistant to attack by the host immune system and facilitate the recurrence of infection. Most species are free-living bacterivores, but some are opportunists that can cause infections in humans and other animals.
Diseases caused by Acanthamoeba include amoebic keratitis and encephalitis (more specifically the Granulomatous amoebic encephalitis). The latter is caused by the Acanthamoeba entering the body through wounds and spreading to the central nervous system.
Acanthamoeba granulomatous encephalitis
This is an opportunistic protozoan pathogen that rarely causes disease in humans. Approximately 400 cases have been reported worldwide, with a survival rate of only two to three percent. Infection usually occurs in patients with immunodeficiency, diabetes, malignancies, malnutrition, systemic lupus erythematosus, or alcoholism. The parasite's portal of entry is via lesions in the skin or the upper respiratory tract or via inhalation of airborne cysts. The parasite then spreads hematogenously into the central nervous system. Acanthamoeba crosses the blood–brain barrier by means that are not yet understood. Subsequent invasion of the connective tissue and induction of pro-inflammatory responses leads to neuronal damage that can be fatal within days. A post mortem biopsy reveals severe oedema and hemorrhagic necrosis. A patient who has contracted this illness usually displays subacute symptoms, including altered mental status, headaches, fever, neck stiffness, seizures, focal neurological signs (such as cranial nerve palsies and coma), all leading to death within one week to several months. Due to the rarity of this parasite and a lack of knowledge, there are currently no good diagnoses or treatments for Acanthamoeba infection. Acanthamoeba Keratitis in past managed by anti-cholinergic drugs, without any antibiotics and/or anti-parasitic drugs, have recently being debated for showing clinical effects due to an anti-parasitic action of their own at Muscarinic cholinergic receptors. 
Infection usually mimics that of bacterial leptomeningitis, tuberculous meningitis, or viral encephalitis. The misdiagnosis often leads to erroneous, ineffective treatment. In the case that the Acanthamoeba is diagnosed correctly, the current treatments, such as amphotericin B, rifampicin, trimethoprim-sulfamethoxazole, ketoconazole, fluconazole, sulfadiazine, or albendazole, are only tentatively successful. Correct and timely diagnosis, as well as improved treatment methods and an understanding of the parasite are important factors in improving the outcome of infection by Acanthamoeba. A recent paper published in 2013, has shown substantial effects of some FDA approved drugs with a kill rate above 90% These results were in-vitro effects, but as the drugs are already approved, human infections can be targeted after dose calculations in clinical trials with them.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in the hospital setting due to its resistance to many antibiotics. Recent findings from the University of Bath demonstrate that MRSA can infect and replicate inside Acanthamoeba polyphaga cells; this species is widespread throughout the environment. Since A. polyphaga can form cysts, cysts infected with MRSA can act as a mode of airborne dispersal for MRSA. Additionally, it is noted that "evidence with other pathogens suggests that pathogens that emerge from amoeba are more resistant to antibiotics and more virulent." Acanthamoeba has been observed to increase MRSA numbers by up to 1000-fold. The Acanthamoeba gets into the body either through the skin or up the nose. It then travels through the nervous system to the brain; once there, it eats brain cells. After feeding, it divides rapidly, causing sudden and massive inflammation, killing the human host in just a few days.
Campylobacter spp. are Gram-negative bacteria that are recognized worldwide as a common cause of acute bacterial enteritis in humans. Acanthamoeba castellanii is a protozoan suspected to serve as a reservoir for bacterial pathogens such as Campylobacter jejuni. . A serious complication of Campylobacter jejuni infection is the development of Guillain–Barré syndrome (GBS). There is increasing evidence that what is diagnosed as Guillain–Barré syndrom may include conditions originating from a variety of underlying pathogenic mechanisms. . For the record, survival of Campylobacter jejuni in co-culture with Acanthamoeba castellanii has been reported in the literature. .
Importance in soil ecology
A. castellanii can be found at high densities in various soil ecosystems. It preys on bacteria, but also fungi and other protozoa.
This species is able to lyse bacteria and produce a wide range of enzymes, such as cellulases or chitinases, and probably contributes to the breakdown of organic matter in soil, contributing to the microbial loop.
Species of Acanthamoeba are distinguished mainly on the form of cysts, and include the following; those marked with an asterisk are known to cause infections.
- A. astronyxis*
- A. byersi*
- A. castellanii*
- A. comandoni
- A. culbertsoni*
- A. divionensis
- A. griffini
- A. hatchetti*
- A. healyi
- A. jacobsi
- A. keratitis*
- A. lenticulata
- A. lugdunensis*
- A. mauritaniensis
- A. palestinensis*
- A. pearcei
- A. polyphaga*
- A. pustulosa
- A. quina*
- A. rhysodes*
- A. royreba
- A. terricola (renamed A. castellanii Poussard)
- A. triangularis
- A. tubiashi
Endosymbiontes of Acanthamoeba
Acanthamoeba spp. contain diverse bacterial endosymbionts that are similar to human pathogens, so they are considered to be potential emerging human pathogens. The exact nature of these symbionts and the benefit they represent for the amoebal host still have to be clarified.
Role as a model organism
Because Acanthamoeba does not differ greatly at the ultrastructural-level from a mammalian cell, it is an attractive model for cell biology studies. Acanthamoeba is important in cellular microbiology, environmental biology, physiology, cellular interactions, molecular biology, biochemistry, and evolutionary studies, due to the organisms' versatile roles in the ecosystem and ability to capture prey by phagocytosis, act as vectors and reservoirs for microbial pathogens, and to produce serious human infections. In addition, Acanthamoeba has been used extensively to understand the molecular biology of cell motility.
Owing to its ease and economy of cultivation, the Neff strain of A. castellanii discovered in a pond in Golden Gate Park in the 1960s, has been effectively used as a classic model organism in the field of cell biology. From just 30 liters of simple medium inoculated with A. castellanii, approximately one kilogram of cells can be obtained after several days of aerated culture at room temperature. Pioneered in the laboratory of Dr. Edward D. Korn at the National Institutes of Health (NIH), many important biological molecules have been discovered and their pathways elucidated using the Acanthamoeba model. Dr. Thomas Dean Pollard applied this model at the NIH, Harvard Medical School, Johns Hopkins University School of Medicine, and the Salk Institute for Biological Studies to discover and characterize many proteins that are essential for cell motility, not only in amoebas, but also in many other eukaryotic cells, especially those of the human nervous and immune systems, the developing embryo, and cancer cells.
When present in the eye, Acanthamoeba strains can cause acanthamoebic keratitis, which may lead to corneal ulcers or even blindness. This condition occurs most often among contact lens wearers who do not properly disinfect their lenses, exacerbated by a failure to wash hands prior to handling the lenses. Multipurpose contact lens solutions are largely ineffective against Acanthamoeba, whereas hydrogen peroxide-based solutions have good disinfection characteristics.
In May 2007, Advanced Medical Optics, manufacturer of Complete Moisture Plus Contact Lens Solution products, issued a voluntary recall of their Complete Moisture Plus solutions. The fear was that contact lens wearers who used their solution were at higher risk of acanthamoebic keratitis than contact lens wearers who used other solutions. The manufacturer recalled the product after the Centers for Disease Control in the United States found that 21 individuals had possibly received an Acanthamoeba infection after using Complete Moisture Plus in the month prior to diagnosis.
Currently Acanthamoeba is the only species that is a host for such huge viruses (who have more than 1000 protein-coding genes; for instance, Pandoravirus has about 2500 protein-coding genes in its genome).
- Acanthamoeba infection
- Acanthamoeba keratitis
- Balamuthia mandrillaris
- Granulomatous amoebic encephalitis
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