Activity of chlorpromazine on nfa1 and Mp2CL5 genes of Naegleria fowleri trophozoites

Tiewcharoen, Supathra; Rabablert, Jundee; Chetannachan, Prucksawan; Worawirunwong, Dusit; Junnu, Virach; Pungsub, Noppamas

doi:10.4236/health.2011.33032

Cited by 4 publications

(5 citation statements)

References 20 publications

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“…Actin proteins related to cell mobility and division and Nf314 serine carboxypeptidase have also been proposed to be potential N. fowleri virulence factors since these proteins were over-expressed in highly virulent N. fowleri trophozoites 7,45 . Another protein named Mp2CL5 was identified as potentially involved in the phagocytosis and cell proliferation 46 . This membrane protein has only been isolated in N. fowleri and has been up-regulated in highly pathogenic N. fowleri 47 .…”

Section: Discussionmentioning

confidence: 99%

Investigation of potential pathogenicity of Willaertia magna by investigating the transfer of bacteria pathogenicity genes into its genome

Hasni

Chelkha

Baptiste

et al. 2019

Sci Rep

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Willaertia magna c2c maky is a thermophilic amoeba closely related to the genus Naegleria. This free-living amoeba has the ability to eliminate Legionella pneumophila, which is an amoeba-resisting bacterium living in an aquatic environment. To prevent the proliferation of L. pneumophila in cooling towers, the use of W. magna as natural biocide has been proposed. To provide a better understanding of the W. magna genome, whole-genome sequencing was performed through the study of virulence factors and lateral gene transfers. This amoeba harbors a genome of 36.5 megabases with 18,519 predicted genes. BLASTp analyses reported protein homology between 136 W. magna sequences and amoeba-resistant microorganisms. Horizontal gene transfers were observed based on the basis of the phylogenetic reconstruction hypothesis. We detected 15 homologs of N. fowleri genes related to virulence, although these latter were also found in the genome of N. gruberi, which is a non-pathogenic amoeba. Furthermore, the cytotoxicity test performed on human cells supports the hypothesis that the strain c2c maky is a non-pathogenic amoeba. This work explores the genomic repertory for the first draft genome of genus Willaertia and provides genomic data for further comparative studies on virulence of related pathogenic amoeba, N. fowleri.

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Section: Discussionmentioning

confidence: 99%

Investigation of potential pathogenicity of Willaertia magna by investigating the transfer of bacteria pathogenicity genes into its genome

Hasni

Chelkha

Baptiste

et al. 2019

Sci Rep

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“…Therefore, in the present study, the antimicrobial properties of bLf and cLz, alone and in combination, were evaluated in N. fowleri cultures. Previously, it was reported that bLf (1.25 µM) does not cause significant negative effects at 12 h of interaction [24]. However, a detailed study on bLf at physiological and high concentrations has not yet been performed.…”

Section: Discussionmentioning

confidence: 97%

“…Regarding N. fowleri, it has been reported that apo-bLf (1 mg/mL) does not induce apoptosis after 12 h of incubation. However, the effects of physiological and higher concentrations of this protein have not been explored [24]. The present study focused on the individual and combined effects of Lf and chicken egg Lz (cLz) on N. fowleri trophozoites.…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin and Lysozyme Inhibit the Proteolytic Activity and Cytopathic Effect of Naegleria fowleri Enzymes

Martinez-Castillo,

Ramírez-Rico,

Shibayama

et al. 2024

Pathogens

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Naegleria fowleri is a ubiquitous free-living amoeba that causes primary amoebic meningoencephalitis. As a part of the innate immune response at the mucosal level, the proteins lactoferrin (Lf) and lysozyme (Lz) are secreted and eliminate various microorganisms. We demonstrate that N. fowleri survives the individual and combined effects of bovine milk Lf (bLf) and chicken egg Lz (cLz). Moreover, amoebic proliferation was not altered, even at 24 h of co-incubation with each protein. Trophozoites’ ultrastructure was evaluated using transmission electron microscopy, and these proteins did not significantly alter their organelles and cytoplasmic membranes. Protease analysis using gelatin-zymograms showed that secreted proteases of N. fowleri were differentially modulated by bLf and cLz at 3, 6, 12, and 24 h. The bLf and cLz combination resulted in the inhibition of N. fowleri-secreted proteases. Additionally, the use of protease inhibitors on bLf-zymograms demonstrated that secreted cysteine proteases participate in the degradation of bLf. Nevertheless, the co-incubation of trophozoites with bLf and/or cLz reduced the cytopathic effect on the MDCK cell line. Our study suggests that bLf and cLz, alone or together, inhibited secreted proteases and reduced the cytopathic effect produced by N. fowleri; however, they do not affect the viability and proliferation of the trophozoites.

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“…16,21,22 Some peptides have also been shown to have activity against FLAs (i.e. N. fowleri, A. globifora, and A. castellanii), [23][24][25][26][27][28] but none have demonstrated activity against B. mandrillaris. Specifically, a tyrocidine-derived linear peptide exhibited IC50 against A. castellanii of 112 μg/mL (88 μM)and 82 μg/mL (64 μM) against N. fowleri at 24 h. 24 Nisin, a ribosomally synthesized post translationally modified peptide produced by Lactococcus lactis, appears to affect the growth of Acanthamoeba, resulting in smaller and rounder trophozoites.…”

Section: Introductionmentioning

confidence: 99%

Discovery of cyclic peptide natural product inhibitors ofBalamuthia mandrillaris

Lu,

Nelson,

Coy

et al. 2024

Preprint

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Balamuthia mandrillaris is a pathogenic free-living amoeba that causes infection of central nervous system, called Balamuthia amoebic encephalitis (BAE), as well as cutaneous and systemic diseases. Patients infected with B. mandrillaris have a high mortality rate due to the lack of effective treatments. A combination of non-optimized antimicrobial drug regimen is typically recommended; however, they have poor parasite activity and can cause various severe side effects. Cyclic peptides exhibit a broad spectrum of antimicrobial activities and lower cytotoxicity. In this study, we evaluated the anti-B. mandrillaris effect of cyclic peptides. The predicted natural product-43 (pNP-43), identified from the SNaPP (Synthetic Natural Product Inspired Cyclic Peptides) library, and its derivates displayed a significant inhibition for B. mandrillaris trophozoites. Eight pNPs had IC50s <5 μM. Furthermore, all hit pNPs demonstrated minimal hemolytic and cytotoxic effects on human cells. Our study first indicates the anti-B. mandrillaris effect of cyclic peptides, which provides a new direction for drug development. Further studies of the mechanism of action and in vivo effects will be elucidated to confirm the potency as a treatment for B. mandrillaris infection in the future.

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Activity of chlorpromazine on nfa1 and Mp2CL5 genes of Naegleria fowleri trophozoites

Cited by 4 publications

References 20 publications

Investigation of potential pathogenicity of Willaertia magna by investigating the transfer of bacteria pathogenicity genes into its genome

Investigation of potential pathogenicity of Willaertia magna by investigating the transfer of bacteria pathogenicity genes into its genome

Lactoferrin and Lysozyme Inhibit the Proteolytic Activity and Cytopathic Effect of Naegleria fowleri Enzymes

Discovery of cyclic peptide natural product inhibitors ofBalamuthia mandrillaris

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