EhSir2c, a Sir2 homolog from the human pathogen <i>Entamoeba histolytica</i> interacts with a DNA repair protein, EhRAD23: Protein-protein interaction, docking and functional study

Biswas, Pinaki; Das, Moubonny; Pal, Suchetana; Ghosh, Raktim; Dam, Somasri

doi:10.1080/07391102.2021.2004925

Cited by 2 publications

(1 citation statement)

References 75 publications

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“…These findings raise a hypothesis that the parasites use the biofilm as a protective layer, potentially to ROS. Several genes involved in E. histolytica response to OS like thioredoxin reductase (EHI_155440) 37 , EhNO1 (EHI_110520) (EhNO1 is mainly involved in ferric reduction) 38 or the DNA damage recognition like the excision repair protein RAD23 (EHI_001400) 39 have their level of expression downregulated in E. histolytica trophozoites exposed to B. subtilis biofilm (table 2). These data suggest that the biofilm protects the parasite against OS.…”

Section: Resultsmentioning

confidence: 99%

Digestive exophagy of Bacterial Biofilms by an Amoeba Predator is Mediated by Specific Biofilm Recognition

Zanditenas

Trebicz-Geffen

Domínguez-García

et al. 2022

Preprint

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The human protozoan parasite Entamoeba histolytica is responsible for amebiasis, a disease endemic to developing countries. E. histolytica trophozoites are released from the cysts to colonize the large intestine, where they primarily feed on bacterial cells. In these scenarios, bacterial cells form aggregates or structured communities too large for phagocytosis. Our results show that E. histolytica can degrade pre-established biofilms of Bacillus subtilis and Escherichia coli in a dose- and time-dependent manner. Surprisingly, trophozoites incubated with B. subtilis biofilm exhibit a unique transcriptome signature compared to those incubated with planktonic cells or without bacteria. Biofilm-induced genes include cysteine proteases (CPs), and the general inhibition of CPs by E64D or by the use of specific small-RNA (sRNA)-based RNA interference impairs the degradation of biofilms by E. histolytica. The degradation of B. subtilis extracellular matrix (ECM) protein TasA by CPs is associated with partial biofilm digestion and activation of the stress response in the interacting B. subtilis cells. The interaction with B. subtilis biofilms was also associated with lower levels of oxidoreductases. Oxidoreductase downregulation can be a readout of the embedding of E. histolytica trophozoites within the biofilm-produced extracellular matrix, reducing their exposure to oxidative stress (OS). Our results indicate that parasites may digest biofilms by a controlled mechanism of digestive exophagy as secretion of digestive enzymes as a conserved mechanism for biofilm degradation allows phagocytic digestion of biofilm cells. Furthermore, the partially digested biofilms can serve as an unexpected shield protecting parasites from oxidative environments and thereby may regulate the persistence and virulence of the parasite.

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Section: Resultsmentioning

confidence: 99%

Digestive exophagy of Bacterial Biofilms by an Amoeba Predator is Mediated by Specific Biofilm Recognition

Zanditenas

Trebicz-Geffen

Domínguez-García

et al. 2022

Preprint

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Digestive exophagy of biofilms by intestinal amoeba and its impact on stress tolerance and cytotoxicity

Zanditenas,

Trebicz-Geffen,

Kolli

et al. 2023

npj Biofilms Microbiomes

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The human protozoan parasite Entamoeba histolytica is responsible for amebiasis, a disease endemic to developing countries. E. histolytica trophozoites colonize the large intestine, primarily feeding on bacteria. However, in the gastrointestinal tract, bacterial cells form aggregates or structured communities called biofilms too large for phagocytosis. Remarkably, trophozoites are still able to invade and degrade established biofilms, utilizing a mechanism that mimics digestive exophagy. Digestive exophagy refers to the secretion of digestive enzymes that promote the digestion of objects too large for direct phagocytosis by phagocytes. E. histolytica cysteine proteinases (CPs) play a crucial role in the degradation process of Bacillus subtilis biofilm. These proteinases target TasA, a major component of the B. subtilis biofilm matrix, also contributing to the adhesion of the parasite to the biofilm. In addition, they are also involved in the degradation of biofilms formed by Gram-negative and Gram-positive enteric pathogens. Furthermore, biofilms also play an important role in protecting trophozoites against oxidative stress. This specific mechanism suggests that the amoeba has adapted to prey on biofilms, potentially serving as an untapped reservoir for novel therapeutic approaches to treat biofilms. Consistently, products derived from the amoeba have been shown to restore antibiotic sensitivity to biofilm cells. In addition, our findings reveal that probiotic biofilms can act as a protective shield for mammalian cells, hindering the progression of the parasite towards them.

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EhSir2c, a Sir2 homolog from the human pathogen Entamoeba histolytica interacts with a DNA repair protein, EhRAD23: Protein-protein interaction, docking and functional study

Cited by 2 publications

References 75 publications

Digestive exophagy of Bacterial Biofilms by an Amoeba Predator is Mediated by Specific Biofilm Recognition

Digestive exophagy of Bacterial Biofilms by an Amoeba Predator is Mediated by Specific Biofilm Recognition

Digestive exophagy of biofilms by intestinal amoeba and its impact on stress tolerance and cytotoxicity

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