Acanthamoeba, an environmental phagocyte enhancing survival and transmission of human pathogens

Rayamajhee, Binod; Willcox, Mark; Henriquez, Fiona L.; Petsoglou, Constantinos; Subedi, Dinesh; Carnt, Nicole

doi:10.1016/j.pt.2022.08.007

Cited by 47 publications

(54 citation statements)

References 117 publications

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“…Furthermore, due to the cellular and functional similarities between A. castellanii and mammalian phagocytic cells, the former are considered as training grounds for these pathogens to later infect humans. 19,20,22 All of these factors make A. castellanii an important and interesting model organism, however, but because of the shortage of molecular biology techniques (among others), it has not been as widely used as other amoebae [19][20][21][22] . Here, we demonstrate that the readily available and inexpensive cationic polymer PEI can be used to transfect A. castellanii with plasmids.…”

Section: Discussionmentioning

confidence: 99%

“…A. castellanii is a free-living protist, ubiquitously and abundantly present in fresh water and soil habitats. It is one of the most often isolated amoebal species worldwide 19,20 . Its status as an emerging human pathogen is due not only to the infections it causes as an opportunistic human pathogen, but also because of its role as a reservoir for bacteria, viruses, and fungi 19,20,21 .…”

Section: Discussionmentioning

confidence: 99%

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High-efficiency transfection ofAcanthamoeba castellaniiusing a cationic polymer

Moreno

Eriksson

et al. 2022

Preprint

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The free-living amoebaAcanthamoeba castellaniiis an ecologically, clinically, and evolutionarily important microorganisms.A. castellaniiamoebae are directly pathogenic to humans, and serve as reservoirs for bacterial pathogens (e.g.,Legionella pneumophila), but also regulate the proliferation of other microorganisms in the soil. Despite their importance, no reliable genetic system has been developed, hampering the use ofA. castellaniiand related species as model organisms. TransfectingA. castellaniiwith plasmids is possible with commercial kits, but is expensive, inefficient, and vulnerable to product discontinuation. In this contribution, we present a method for efficient transfection ofA. castellaniiwith readily available and inexpensive polyethylenimines. We systematically explore the parameters of the method, obtaining up to 100-fold higher efficiency than currently used reagents. The method presented here provides a robust step towards a full genetic toolbox forA. castellanii, hence expanding its use as a model organism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High-efficiency transfection ofAcanthamoeba castellaniiusing a cationic polymer

Moreno

Eriksson

et al. 2022

Preprint

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“…Amoebae have been particularly well studied as a potential source of environmental selective pressure on diverse microbes given their similarities to the macrophages of animal immune systems. Like macrophages, amoebae can phagocytose microorganisms, and undergo many similar processes following phagocytosis including phagosome maturation and acidification 13 . Studies of bacterial species, like Legionella pneumophila, have identified virulence factors that are required for success in both specific amoeba species and mammalian host cells, providing strong evidence that similarities across amoeba and mammalian host cell environments could select for broadly effective virulence strategies [14][15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

Distinct pathways of adaptive evolution inCryptococcus neoformansreveal a point mutation in adenylate cyclase with drastic tradeoffs for pathogenicity

Hilbert¹,

Chung²,

Bednarek³

et al. 2022

Preprint

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Pathogenic fungi populate a wide range of environments and infect a diversity of host species. Despite this substantial biological flexibility, the impact of interactions between fungi and their hosts on the evolution of pathogenicity remains unclear. We studied how repeated interactions between the fungus Cryptococcus neoformans and relevant environmental and mammalian host cells, amoeba and mouse macrophages, shape the evolution of this model fungal pathogen. First, using a collection of clinical and environmental isolates of C. neoformans, we characterized a range of survival phenotypes for these strains when exposed to host cells of different species. We then performed serial passages of an environmentally isolated C. neoformans strain through either amoeba or macrophages for ~75 generations to observe how these interactions select for improved replication within hosts. In an adapted population, we identified a single point mutation in the adenylate cyclase gene, CAC1, that swept to fixation and confers a strong competitive advantage for growth inside of macrophages. Strikingly, this growth advantage in macrophages is inversely correlated with disease severity during mouse infections, suggesting that adaptations to specific host niches can markedly reduce the pathogenicity of these fungi. These results raise intriguing questions about the influence of cAMP signaling on pathogenicity and highlight the role of seemingly small adaptive changes in promoting fundamental shifts in the intracellular behavior and virulence of these important human pathogens.

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“…Acanthamoeba castellanii ( A. castellanii ) is a ubiquitous free-living amoeba isolated from soil, dust, treated and untreated water, air-conditioning units, contact lenses, ophthalmological solutions, dialysis units, surgical material, fecal material, human throats mucosa, and even air [ 1 , 2 , 3 , 4 ]. This amphizoic microorganism is a reported etiological agent of a frequently misdiagnosed sight-threating corneal infection, Acanthamoeba keratitis, resulting from corneal abrasion due to exposure to heavily contaminated liquid [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…This is likely due to the increasing numbers of contact lens users and/or global warming associated with outdoor water-related activities/poor compliance in the use of contact lenses. After gaining entry hematogenously, through the lower respiratory tract, skins ulcers, or through the olfactory epithelium, Acanthamoeba can also bring about a fatal brain infection mainly in immunocompromised patients: granulomatous amoebic encephalitis [ 2 , 4 ]. Notably, Acanthamoeba can also engender skin nodules and abscesses [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Antiamoebic Properties of Ceftriaxone and Zinc-Oxide–Cyclodextrin-Conjugated Ceftriaxone

et al. 2022

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Acanthamoeba castellanii is a ubiquitous free-living amoeba capable of instigating keratitis and granulomatous amoebic encephalitis in humans. Treatment remains limited and inconsistent. Accordingly, there is a pressing need for novel compounds. Nanotechnology has been gaining attention for enhancing drug delivery and reducing toxicity. Previous work has shown that various antibiotic classes displayed antiamoebic activity. Herein, we employed two antibiotics: ampicillin and ceftriaxone, conjugated with the nanocarrier zinc oxide and β-cyclodextrin, and tested them against A. castellanii via amoebicidal, amoebistatic, encystment, excystment, cytopathogenicity, and cytotoxicity assays at a concentration of 100 μg/mL. Notably, zinc oxide β-cyclodextrin ceftriaxone significantly inhibited A. castellanii growth and cytopathogenicity. Additionally, both zinc oxide β-cyclodextrin ceftriaxone and ceftriaxone markedly inhibited A. castellanii encystment. Furthermore, all the tested compounds displayed negligible cytotoxicity. However, minimal anti-excystment or amoebicidal effects were observed for the compounds. Accordingly, this novel nanoconjugation should be employed in further studies in hope of discovering novel anti-Acanthamoeba compounds.

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Acanthamoeba, an environmental phagocyte enhancing survival and transmission of human pathogens

Cited by 47 publications

References 117 publications

High-efficiency transfection ofAcanthamoeba castellaniiusing a cationic polymer

High-efficiency transfection ofAcanthamoeba castellaniiusing a cationic polymer

Distinct pathways of adaptive evolution inCryptococcus neoformansreveal a point mutation in adenylate cyclase with drastic tradeoffs for pathogenicity

Antiamoebic Properties of Ceftriaxone and Zinc-Oxide–Cyclodextrin-Conjugated Ceftriaxone

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