Drugs used for the treatment of cerebral and disseminated infections caused by free‐living amoebae

Taravaud, Alexandre; Fechtali-Moute, Zineb; Loiseau, Philippe M.; Pomel, Sébastien

doi:10.1111/cts.12955

Cited by 30 publications

(27 citation statements)

References 87 publications

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“…All of these survivors were treated with amphotericin B, and most also received an azole, rifampin, azithromycin, and miltefosine ( 7 ). Taravaud et al compiled case reports in an extensive literature review to show trends in treatment selections and reported that amphotericin B and rifampicin are used most frequently, with fluconazole, azithromycin, and miltefosine trailing close behind ( 8 ). The frequent use of these drugs combined with the lack of successful outcomes leads us to speculate that there are other factors at play among amoeba populations that could contribute to treatment failure.…”

Section: Introductionmentioning

confidence: 99%

Differential Growth Rates and In Vitro Drug Susceptibility to Currently Used Drugs for Multiple Isolates of Naegleria fowleri

Russell

Kyle

2022

Microbiol Spectr

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Section: Introductionmentioning

confidence: 99%

Differential Growth Rates and In Vitro Drug Susceptibility to Currently Used Drugs for Multiple Isolates of Naegleria fowleri

Russell

Kyle

2022

Microbiol Spectr

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“…Importantly, this FLA can also give rise to granulomatous amoebic encephalitis for which no effective monotherapy is presently available. Despite the use of current therapies empirically associating a large cocktail of drugs, a high mortality is observed, above 90% of the cases ( Visvesvara et al, 2007 ; Taravaud et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Acanthamoeba castellanii excystment by enzyme treatment and consequences on trophozoite growth

Fechtali-Moute

Loiseau

Pomel

2022

Front. Cell Dev. Biol.

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Acanthamoeba castellanii is a widespread Free-Living Amoeba (FLA) that can cause severe ocular or cerebral infections in immunocompetent and immunocompromised patients, respectively, besides its capacity to transport diverse pathogens. During their life cycle, FLA can alternate between a vegetative form, called a trophozoite, and a latent and resistant form, called a cyst. This resistant form is characterized by the presence of a cell wall containing two layers, namely the ectocyst and the endocyst, mainly composed of cellulose and proteins. In the present work, we aimed to stimulate Acanthamoeba castellanii excystment by treating their cysts with a cellulolytic enzyme, i.e., cellulase, or two proteolytic enzymes, i.e., collagenase and pepsin. While 11 days were necessary to obtain total excystment in the control at 27°C, only 48 h were sufficient at the same temperature to obtain 100% trophozoites in the presence of 25 U/mL cellulase, 50 U/mL collagenase or 100 U/mL pepsin. Additionally, more than 96% amoebae have excysted after only 24 h with 7.5 U/mL cellulase at 30°C. Nevertheless, no effect of the three enzymes was observed on the excystment of Balamuthia mandrillaris and Vermamoeba vermiformis. Surprisingly, A. castellanii trophozoites excysted in the presence of cellulase displayed a markedly shorter doubling time at 7 h, in comparison to the control at 23 h. Likewise, trophozoites doubled their population in 9 h when both cellulose and cellulase were added to the medium, indicating that Acanthamoeba cyst wall degradation products promote their trophozoite proliferation. The analysis of cysts in epifluorescent microscopy using FITC-lectins and in electron microscopy revealed a disorganized endocyst and a reduction of the intercystic space area after cellulase treatment, implying that these cellular events are preliminary to trophozoite release during excystment. Further studies would be necessary to determine the signaling pathways involved during this amoebal differentiation process to identify new therapeutic targets for the development of anti-acanthamoebal drugs.

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“…The standard drug to treat this disease is the antibiotic amphotericin B. However, the case fatality rate remains higher than 95%, even after opportune drug therapy [ 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections

Madero-Ayala

Mares-Alejandre

Ramos

2022

IJMS

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Naegleria fowleri, also known as the “brain-eating” amoeba, is a free-living protozoan that resides in freshwater bodies. This pathogenic amoeba infects humans as a casual event when swimming in contaminated water. Upon inhalation, N. fowleri invades the central nervous system and causes primary amoebic meningoencephalitis (PAM), a rapidly progressive and often fatal disease. Although PAM is considered rare, reducing its case fatality rate compels the search for pathogen-specific proteins with a structure–function relationship that favors their application as targets for discovering new or improved drugs against N. fowleri infections. Herein, we report a computational approach to study the structural features of Nf314 (a serine carboxypeptidase that is a virulence-related protein in N. fowleri infections) and assess its potential as a drug target, using bioinformatics tools and in silico molecular docking experiments. Our findings suggest that Nf314 has a ligand binding site suitable for the structure-based design of specific inhibitors. This study represents a further step toward postulating a reliable therapeutic target to treat PAM with drugs specifically aimed at blocking the pathogen proliferation by inhibiting protein function.

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Drugs used for the treatment of cerebral and disseminated infections caused by free‐living amoebae

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 30 publications

References 87 publications

Differential Growth Rates and In Vitro Drug Susceptibility to Currently Used Drugs for Multiple Isolates of Naegleria fowleri

Differential Growth Rates and In Vitro Drug Susceptibility to Currently Used Drugs for Multiple Isolates of Naegleria fowleri

Stimulation of Acanthamoeba castellanii excystment by enzyme treatment and consequences on trophozoite growth

In Silico Structural Analysis of Serine Carboxypeptidase Nf314, a Potential Drug Target in Naegleria fowleri Infections

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