Antioxidant defence systems in the protozoan pathogen Giardia intestinalis

Mastronicola, Daniela; Falabella, Micol; Forte, Elena; Testa, Fabrizio; Sarti, Paolo; Giuffrè, Alessandro

doi:10.1016/j.molbiopara.2015.12.002

Cited by 25 publications

(23 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The production of reactive oxygen species (ROS) represents one of the main epithelial cell defenses to fight off trophozoites early during infection (Ma'ayeh et al, 2015). Nevertheless, the ability of microaerophilic trophozoites to counteract host oxidative defenses has been investigated previously in vitro, highlighting the roles of the thioredoxin system, NADH oxidases, peroxiredoxins oxidoreductases, nitroreductases and nicotinamide co-factors in neutralizing host ROS (Ma'ayeh et al, 2015;Mastronicola et al, 2016;Pham et al, 2017). In fact, the genes encoding the above enzymes were differentially expressed at 1.5 h and thereafter ( Supplementary Tables S2-S4), corroborating the above findings.…”

Section: Discussionmentioning

confidence: 99%

High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions

Peirasmaki

Ma’ayeh

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Giardia intestinalis colonizes the upper small intestine of humans and animals, causing the diarrheal disease giardiasis. This unicellular eukaryotic parasite is not invasive but it attaches to the surface of small intestinal epithelial cells (IECs), disrupting the epithelial barrier. Here, we used an in vitro model of the parasite's interaction with host IECs (differentiated Caco-2 cells) and RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) in Giardia, which might relate to the establishment of infection and disease induction. Giardia trophozoites interacted with differentiated Caco-2 cells for 1.5, 3, and 4.5 h and at each time point, 61, 89, and 148 parasite genes were up-regulated more than twofold, whereas 209, 265, and 313 parasite genes were down-regulated more than twofold. The most abundant DEGs encode hypothetical proteins and members of the High Cysteine Membrane Protein (HCMP) family. Among the up-regulated genes we also observed proteins associated with proteolysis, cellular redox balance, as well as lipid and nucleic acid metabolic pathways. In contrast, genes encoding kinases, regulators of the cell cycle and arginine metabolism and cytoskeletal proteins were down-regulated. Immunofluorescence imaging of selected, up-regulated HCMPs, using C-terminal HA-tagging, showed localization to the plasma membrane and peripheral vesicles (PVs). The expression of the HCMPs was affected by histone acetylation and free iron-levels. In fact, the latter was shown to regulate the expression of many putative giardial virulence factors in subsequent RNAseq experiments. We suggest that the plasma membrane localized and differentially expressed HCMPs play important roles during Giardia-host cell interactions.

show abstract

Section: Discussionmentioning

confidence: 99%

High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions

Peirasmaki

Ma’ayeh

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…Curiously, some parasitic protozoans lack SODs altogether. Such is the case for the intestinal pathogen and anaerobe Giardia intestinalis , which instead contains a cytosolic superoxide reductase (SOR) 168 . SORs catalyze the conversion of O 2 ·− into H 2 O 2 in the presence of a reductant.…”

Section: Protist Pathogensmentioning

confidence: 99%

Chemical Warfare at the Microorganismal Level: A Closer Look at the Superoxide Dismutase Enzymes of Pathogens

Schatzman

Culotta

2018

ACS Infect. Dis.

View full text Add to dashboard Cite

Superoxide anion radical is generated as a natural byproduct of aerobic metabolism, but is also produced as part of the oxidative burst of the innate immune response design to kill pathogens. In living systems, superoxide is largely managed through superoxide dismutases (SODs), families of metalloenzymes that use Fe, Mn, Ni or Cu cofactors to catalyze the disproportionation of superoxide to oxygen and hydrogen peroxide. Given the bursts of superoxide faced by microbial pathogens, it comes as no surprise that SOD enzymes play important roles in microbial survival and virulence. Interestingly, microbial SOD enzymes not only detoxify host superoxide, but may also participate in signaling pathways that involve reactive oxygen species derived from the microbe itself, particularly in the case of eukaryotic pathogens. In this review, we will discuss the chemistry of superoxide radicals and the role of diverse SOD metalloenzymes in bacterial, fungal, and protozoan pathogens. We will highlight the unique features of microbial SOD enzymes that have evolved to accommodate the harsh lifestyle at the host-pathogen interface. Lastly, we will discuss key non-SOD superoxide scavengers that specific pathogens employ for defense against host superoxide.

show abstract

“…(A, B: ****P < 0.0001; C: ****P < 0.0001, ***P = 0.0004, **P = 0.0024; D: ****P < 0.0001, **P = 0.0062, *P = 0.0310, *P = 0.0143; E: ****P < 0.0001) against H 2 O 2 and ONOO − radicals, participating as important virulence factors. 71,72 In conclusion, we demonstrated the importance of the MPO enzyme and its relation with the production of pro-oxidant metabolites produced by neutrophils. However, N. fowleri possesses important antioxidant machinery to evade the robust arsenal evolved by neutrophils (Supporting Information Fig.…”

Section: F I G U R E 8 Analysis Of Relative Expression Of Antioxidantmentioning

confidence: 55%

The MPO system participates actively in the formation of an oxidative environment produced by neutrophils and activates the antioxidant mechanism of Naegleria fowleri

Flores-Huerta

Pacheco‐Yépez

Sánchez-Monroy

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Naegleria fowleri produces a fatal disease called primary amebic meningoencephalitis (PAM), which is characterized by an extensive inflammatory reaction in the CNS. It is known that the immune response is orchestrated mainly by neutrophils, which activate several defense mechanisms in the host, including phagocytosis, the release of different enzymes such as myeloperoxidase (MPO), and the production of neutrophil extracellular traps. However, the mechanisms by which amoebas evade the neutrophil response are still unknown. In this study, we analyzed the ability of N. fowleri to respond to the stress exerted by MPO. Interestingly, after the interaction of trophozoites with neutrophils, the amoeba viability was not altered; however, ultrastructural changes were observed. To analyze the influence of MPO against N. fowleri and its participation in free radical production, we evaluated its enzymatic activity, expression, and localization with and without the specific 4‐aminobenzoic acid hydrazide inhibitor. The production of oxidizing molecules is the principal mechanism used by neutrophils to eliminate pathogens. In this context, we demonstrated an increase in the production of NO, superoxide anion, and reactive oxygen species; in addition, the overexpression of several antioxidant enzymes present in the trophozoites was quantified. The findings strongly suggest that N. fowleri possesses antioxidant machinery that is activated in response to an oxidative environment, allowing it to evade the neutrophil‐mediated immune response, which may contribute to the establishment of PAM.

show abstract

Antioxidant defence systems in the protozoan pathogen Giardia intestinalis

Cited by 25 publications

References 125 publications

High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions

High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions

Chemical Warfare at the Microorganismal Level: A Closer Look at the Superoxide Dismutase Enzymes of Pathogens

The MPO system participates actively in the formation of an oxidative environment produced by neutrophils and activates the antioxidant mechanism of Naegleria fowleri

Contact Info

Product

Resources

About