Infection is generally associated with underlying conditions such as immunodeficiency, diabetes, malignancies, malnutrition, systemic lupus erythematosus, and alcoholism. The parasite enters the body through cuts in the skin or by being inhaled into the upper respiratory tract. The parasite then spreads through the blood into the CNS. 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. Pure granulomatous lesions are rare in patients with AIDS and other related immunodeficiency states, as the patients do not have adequate numbers of CD+ve T-cells to mount a granulomatous response to Acanthamoeba infection in CNS and other organs and tissues. A perivascular cuffing with amoebae in necrotic tissue is usual finding in the AIDS and related T-cell immunodeficiency conditions. Brain biopsy normally 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, and 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, no good diagnoses or treatments for Acanthamoeba infection are now known. Acanthamoeba keratitis cases in the past have resolved from a therapy consisting of atropine and some other drugs with no antimicrobial effects.
Pioneered in the laboratory of 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. 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 amoebae, but also in many other eukaryotic cells, especially those of the human nervous and immune systems, the developing embryo, and cancer cells. Acanthamoeba also has served as a model to study the evolution of certain G-proteins. This unicellular eukaryote expresses few GPCRs over its cell membrane that serve vital role for the microorganism, structural homology bioinformatics tools have been used to show the presence of a homolog of human M1-muscarinic receptor in A. castellanii. Blocking these muscarinic receptors in past studies has proven to be amoebicidal in Acanthamoeba spp. More recently, voltage-gated calcium channels in Acanthamoeba spp. (CavAc) have been reported to have similarities with human voltage-gated calcium channels such as TPC-1 and L-type calcium channels and respond to Ca-channel blockers such as loperamide. This model microbe has been studied to understand complex neurodegenerative states including Alzheimers disease. Scientists have isolated a neurotransmitter acetylcholine in Acanthamoeba and the enzymatic machinery needed for its synthesis. Endosymbionts
Acanthamoeba spp. contain diverse bacterial endosymbionts that are similar to human pathogens, so they are considered to be potential emerging human pathogens.