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Antimicrobial Agents and Chemotherapy Nov 2016For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis,... (Review)
Review
For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Amphotericin B; Animals; Antiprotozoal Agents; Azoles; Biguanides; Caspofungin; Cefazolin; Chlorhexidine; Echinocandins; Humans; Infectious Encephalitis; Lipopeptides; Meropenem; Natamycin; Polymyxin B; Thienamycins
PubMed: 27600042
DOI: 10.1128/AAC.00686-16 -
International Journal of Antimicrobial... Oct 2020Acanthamoebae are facultative parasites causing rare but serious infections such as keratitis and encephalitis and are also known as vectors for several bacterial...
Acanthamoebae are facultative parasites causing rare but serious infections such as keratitis and encephalitis and are also known as vectors for several bacterial pathogens, including legionellae and pseudomonads. Acanthamoeba cysts are particularly resilient and enable the amoebae to withstand desiccation and to resist disinfection and therapy. While the search for new therapeutic options has been intensified in the past years, hand and surface disinfectants as well as topical antiseptics for preventing infections have not been studied in detail to date. The aim of this study was to screen well-known and commonly used antimicrobial products in various formulations and different concentrations for their efficacy against Acanthamoeba trophozoites and cysts, including aliphatic alcohols, quaternary ammonium compounds (QACs), peracetic acid (PAA), potassium peroxymonosulfate sulfate (PPMS) and octenidine dihydrochloride (OCT). Of all products tested, OCT and QACs showed the highest efficacy, totally eradicating both trophozoites and cysts within 1 min. The determined 50% effective concentration (EC) for cysts was 0.196 mg/mL for OCT and 0.119 mg/mL for QACs after 1 min of exposure. PAA and PPMS showed reliable cysticidal efficacies only with prolonged incubation times of 30 min and 60 min, respectively. Aliphatic alcohols generally had limited efficacy, and only against trophozoites. In conclusion, OCT and QACs are potent actives against Acanthamoeba trophozoites and cysts at concentrations used in commercially available products, within contact times suitable for surface and hand disinfection as well as topical antisepsis.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Alcohols; Antiparasitic Agents; Disinfectants; Disinfection; Hand Disinfection; Humans; Imines; Peracetic Acid; Pyridines; Quaternary Ammonium Compounds; Sulfuric Acids; Trophozoites
PubMed: 32739477
DOI: 10.1016/j.ijantimicag.2020.106122 -
The Korean Journal of Parasitology Aug 2019Acanthamoeba, one of free-living amoebae (FLA), remains a high risk of direct contact with this protozoan parasite which is ubiquitous in nature and man-made... (Review)
Review
Acanthamoeba, one of free-living amoebae (FLA), remains a high risk of direct contact with this protozoan parasite which is ubiquitous in nature and man-made environment. This pathogenic FLA can cause sight-threatening amoebic keratitis (AK) and fatal granulomatous amoebic encephalitis (GAE) though these cases may not commonly be reported in our clinical settings. Acanthamoeba has been detected from different environmental sources namely; soil, water, hot-spring, swimming pool, air-conditioner, or contact lens storage cases. The identification of Acanthamoeba is based on morphological appearance and molecular techniques using PCR and DNA sequencing for clinico-epidemiological purposes. Recent treatments have long been ineffective against Acanthamoeba cyst, novel anti-Acanthamoeba agents have therefore been extensively investigated. There are efforts to utilize synthetic chemicals, lead compounds from medicinal plant extracts, and animal products to combat Acanthamoeba infection. Applied nanotechnology, an advanced technology, has shown to enhance the anti-Acanthamoeba activity in the encapsulated nanoparticles leading to new therapeutic options. This review attempts to provide an overview of the available data and studies on the occurrence of pathogenic Acanthamoeba among the Association of Southeast Asian Nations (ASEAN) members with the aim of identifying some potential contributing factors such as distribution, demographic profile of the patients, possible source of the parasite, mode of transmission and treatment. Further, this review attempts to provide future direction for prevention and control of the Acanthamoeba infection.
Topics: Acanthamoeba; Amebiasis; Asia, Southeastern; Soil; Water
PubMed: 31533401
DOI: 10.3347/kjp.2019.57.4.341 -
The Yale Journal of Biology and Medicine Jun 2017keratitis (AK) is a rare but sight-threatening disease caused by pathogenic species of . Despite its ubiquitous nature, the incidence of AK is relatively low compared... (Review)
Review
keratitis (AK) is a rare but sight-threatening disease caused by pathogenic species of . Despite its ubiquitous nature, the incidence of AK is relatively low compared to other forms of infectious keratitis. Although contact lens wear is a major risk factor, exposure to contaminated water and ocular trauma are also associated with AK. Once a patient develops AK the prognosis is very poor unless an aggressive treatment regimen is initiated early. Some of the intriguing features of AK are the lack of immunological memory, resistance of the dormant cyst form to treatment, differences between the pathogenic strains and soil isolates of and the unique role of the innate immune system in controlling this disease. Understanding the series of steps involved in the pathogenesis of the disease and the host immune response against antigens is crucial for developing effective therapeutic strategies targeting the disease.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Adaptive Immunity; Animals; Complement System Proteins; Cornea; Disease Models, Animal; Humans; Immunity, Innate; Immunity, Mucosal; Risk Factors; Toll-Like Receptors
PubMed: 28656012
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Feb 2023Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe...
Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1'-methoxyamentadione (5) and 6Z-1'-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ to Δ of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba.
Topics: Animals; Humans; Acanthamoeba castellanii; Amebicides; Trophozoites; Actin Cytoskeleton
PubMed: 36916403
DOI: 10.1016/j.biopha.2022.114185 -
Frontiers in Cellular and Infection... 2018Environmental bacteria of the genus naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow... (Review)
Review
Environmental bacteria of the genus naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the -containing vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of "effector" proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit. The mechanism of LCV formation appears to be evolutionarily conserved, and therefore, amoebae are not only ecologically significant niches for spp., but also useful cellular models for eukaryotic phagocytes. In particular, and emerged over the last years as versatile and powerful models. Using genetic, biochemical and cell biological approaches, molecular interactions between amoebae and have recently been investigated in detail with a focus on the role of phosphoinositide lipids, small and large GTPases, autophagy components and the retromer complex, as well as on bacterial effectors targeting these host factors.
Topics: Acanthamoeba; Acanthamoeba castellanii; Amoeba; Animals; Autophagy; Bacterial Proteins; Dictyostelium; Disease Models, Animal; Drug Evaluation, Preclinical; Evolution, Molecular; GTP Phosphohydrolases; Host-Pathogen Interactions; Legionella; Legionella pneumophila; Legionnaires' Disease; Macrophages; Phosphatidylinositols; Proteomics; Type IV Secretion Systems; Vacuoles
PubMed: 29552544
DOI: 10.3389/fcimb.2018.00061 -
Frontiers in Cellular and Infection... 2018
Topics: Acanthamoeba; Biomedical Research; DNA Mutational Analysis; Host-Pathogen Interactions; Legionella; Legionnaires' Disease; Microbial Viability; Virulence; Virulence Factors; Water Microbiology
PubMed: 30283746
DOI: 10.3389/fcimb.2018.00328 -
Journal of the American Veterinary... Dec 2020A 12-year-old neutered male domestic shorthair cat with chronic anterior uveitis and secondary glaucoma of the right eye was examined for persistent blepharospasm 2...
CASE DESCRIPTION
A 12-year-old neutered male domestic shorthair cat with chronic anterior uveitis and secondary glaucoma of the right eye was examined for persistent blepharospasm 2 weeks after corneal debridement and grid keratotomy for nonhealing superficial ulcerative keratitis.
CLINICAL FINDINGS
Examination of the right eye revealed a central superficial corneal ulcer associated with corneal epithelial and subepithelial infiltrates and mild aqueous flare. Structures consistent with amoeboid cysts and trophozoites were detected in the cornea by in vivo confocal microscopy. Suppurative keratitis was identified cytologically. An spp was isolated through culture and identified by a PCR assay of corneal specimens.
TREATMENT AND OUTCOME
Symptomatic and antiamoebic (polyhexamethylene biguanide 0.02% ophthalmic solution) treatments were instituted. Over the following 6 weeks, the cat lost vision in the affected eye and lesions progressed to nonulcerative stromal keratitis associated with a dense paracentral corneal stroma ring infiltrate and anterior lens luxation. The globe was enucleated, and lymphoplasmacytic sclerokeratitis, anterior uveitis, and retinal detachment were noted. organisms were detected within the corneal stroma and anterior sclera with histologic and immunohistochemical stains. The amoebae were classified to the T4 genotype by DNA sequencing. The cat had no medical problems attributed to infection over 36 months after enucleation, until the cat was lost to follow-up.
CLINICAL RELEVANCE
Naturally acquired sclerokeratitis is described in a cat for the first time. infection should be considered for cats with superficial corneal disease refractory to appropriate treatments and especially occurring after ocular trauma, including keratotomy.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Animals; Cat Diseases; Cats; Cornea; Corneal Stroma; Corneal Ulcer; Male
PubMed: 33269959
DOI: 10.2460/javma.257.12.1280 -
Middle East African Journal of... 2019Natural honey in spite of its usefulness is known to contain certain microorganisms. In the present study, we describe a case of after using topical honey administered...
Natural honey in spite of its usefulness is known to contain certain microorganisms. In the present study, we describe a case of after using topical honey administered by a traditional medicine therapist. A 32-year-old male came with red eye and blurred vision. The pain and other symptoms became more severe after the 1st week, with appearance of radial perineuritis at the cornea. A repeated interview revealed that 1 week before appearance of ocular symptoms, the patient had instilled a drop of natural honey in his left eye. Confocal microscopic cornea imaging demonstrated cyst and trophozoite of in the corneal stroma.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Adult; Honey; Humans; Male; Vision Disorders
PubMed: 32153338
DOI: 10.4103/meajo.MEAJO_56_18 -
Antimicrobial Agents and Chemotherapy Jun 2022Infection with pathogenic free-living amoebae, including Naegleria fowleri, spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because...
Infection with pathogenic free-living amoebae, including Naegleria fowleri, spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (Glck) as a potential target for therapeutic intervention, as glucose metabolism is critical for viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (Glck) and (Glck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP, Glck and Glck have apparent values of 472.5 and 41.0 μM, while Homo sapiens Glck (Glck) has a value of 310 μM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent values of 45.9 μM (Glck) and 124 μM (Glck) compared to ~8 mM for Glck. Additionally, Glck and Glck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Glucokinase; Humans; Naegleria fowleri
PubMed: 35604214
DOI: 10.1128/aac.02373-21