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Pathogens
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Pathogenesis and Treatment of Giardiasis
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Pathogenesis and Treatment of Giardiasis

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 4990

Special Issue Editors

Dr. Renata Rosito Tonelli

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Guest Editor
Departamento de Ciências Famacêticas, Universidade Federal de São Paulo, Diadema, Brazil
Interests: cell biology of Giardia lamblia; pathophysiological mechanisms in giardiasis
Dr. Semíramis Guimarães

E-Mail Website1 Website2
Guest Editor
Departamento de Biodiversidade e Bioestatística, Instituto de Biociências, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo 18168-689, Brazil
Interests: parasitology; intestinal protozoa; epidemiology; genetic diversity

Special Issue Information

Dear Colleagues,

Giardia lamblia (syn., G. intestinalis, G. duodenalis) is a protozoan parasite that causes acute diarrhea in humans. Giardiasis, the disease caused by Giardia species, is a widespread infection transmitted among humans and occasionally from animals to humans. Direct contact with contaminated feces or feces-contaminated water and food is the main source of infection. Although distributed worldwide, infection with Giardia tends to occur in confined outbreaks, especially in low- and middle-income countries, with or without poor water supply and sanitation. The disease is characterized by flatulence, abdominal distention and cramps followed by watery diarrhea that later becomes bulky and greasy. Giardiasis is self-limiting in most of infected individuals, but can evolve to chronic or post-infectious gastrointestinal complications. In poor-resource settings, giardiasis is considered a public health problem because it is associated with malnutrition and growth failure in young children.

Substantial progress is being made in understanding the pathogenesis and potential pathophysiological mechanisms behind Giardia-associated diarrhea, and this may lead to novel therapeutic approaches. This Special Issue aims to gather contributions from basic sciences and clinical research to examine the pathophysiology, clinical features, and therapy in giardiasis. 

Dr. Renata Rosito Tonelli
Dr. Semíramis Guimarães
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • infectious diasease
  • intestinal parasite
  • diarrhea
  • pathophysiological mechanisms
  • therapy

Published Papers (3 papers)

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Research

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10 pages, 1485 KiB  
Article
Catalytic Differences between Flavohemoglobins of Giardia intestinalis and E. coli
by Sarah Hill, Isabelle Decorso, Novin Nezamololama, Zahra Babaei and Steven Patrick Rafferty
Pathogens 2024, 13(6), 480; https://doi.org/10.3390/pathogens13060480 - 6 Jun 2024
Viewed by 664
Abstract
The sole known heme enzyme of the parasitic protist Giardia intestinalis is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free radical nitric oxide. To learn more about the properties of this enzyme, we [...] Read more.
The sole known heme enzyme of the parasitic protist Giardia intestinalis is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free radical nitric oxide. To learn more about the properties of this enzyme, we measured its nitric oxide dioxygenase, NADH oxidase, and cytochrome c reductase activities and compared these to the activities of the E. coli flavohemoglobin (Hmp). The turnover number for the NOD activity of gFlHb (23 s−1) is about two-thirds of that of Hmp (34 s−1) at pH 6.5 and 37 °C. The two enzymes differ in their sensitivity towards molecules that act as heme ligands. For both gFlHb and Hmp, inhibition with miconazole, a large imidazole ligand, is adequately described by simple competitive inhibition, with KI = 10 μM and 0.27 μM for gFlHb and Hmp, respectively. Inhibition plots with the small ligand imidazole were biphasic, which is consistent with previous experiments with carbon monoxide as a probe that show that the active site of flavohemoglobins exists in two conformations. Interestingly, the largest difference is observed with nitrite, which, like imidazole, also shows a biphasic inhibition plot; however, nitrite inhibits gFlHb at sub-millimolar concentrations while Hmp is not significantly affected. NADH oxidase activity measured under aerobic conditions in the absence of nitric oxide for Hmp was more than twice the activity of gFlHb. The addition of 1 mM hydrogen peroxide in these assays stimulated the NADH oxidase activity of gFlHb but not Hmp. Both enzymes had nearly identical cytochrome c reductase activities but the extent of the contribution of indirect reduction by flavohemoglobin-generated superoxide was much lower with gFlHb (4% SOD-inhibited) than with Hmp (17% SOD-inhibited). Although the active sites of the two enzymes share the same highly conserved residues that are important for catalysis, differences in the distal ligand binding site may account for these differences in activity and sensitivity towards NOD inhibitors. The differences observed in the NADH oxidase and cytochrome c reductase assays suggest that gFlHb may have evolved to protect the protist, which lacks both superoxide dismutase and catalase, from the damaging effects of superoxide by minimizing its production and from peroxide by actively reducing it. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Giardiasis)
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15 pages, 5716 KiB  
Article
Assessment of Drug Activities against Giardia Using Hyperspectral Raman Microscopy
by Felicia S. Manciu, Jose Guerrero, Breanna C. Pence, Lizbeth V. Martinez Lopez and Siddhartha Das
Pathogens 2024, 13(5), 358; https://doi.org/10.3390/pathogens13050358 - 27 Apr 2024
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Abstract
This study demonstrates the capability of Raman microscopy for detecting structural differences in Giardia cells exposed to different drugs and incubation times. While metronidazole (MTZ) visibly affects the cells by inducing extracellular vesicle releases of toxic iron intermediates and modified triple-bond moieties, oseltamivir [...] Read more.
This study demonstrates the capability of Raman microscopy for detecting structural differences in Giardia cells exposed to different drugs and incubation times. While metronidazole (MTZ) visibly affects the cells by inducing extracellular vesicle releases of toxic iron intermediates and modified triple-bond moieties, oseltamivir (OSM) alters the phenylalanine and lipid structures. Modifications in the heme protein environment and the transformation of iron from ferric to ferrous observed for both drug treatments are more notable for MTZ. Different contents and amounts of vesicle excretion are detected for 24 h or 48 h with MTZ incubation. At a shorter drug exposure, releases of altered proteins, glycogen, and phospholipids dominate. Agglomerates of transformed iron complexes from heme proteins and multiple-bond moieties prevail at 48 h of treatment. No such vesicle releases are present in the case of OSM usage. Drug incorporations into the cells and their impact on the plasma membrane and the dynamics of lipid raft confirmed by confocal fluorescence microscopy reveal a more destructive extent by OSM, corroborating the Raman results. Raman microscopy provides a broader understanding of the multifaceted factors and mechanisms responsible for giardiasis treatment or drug resistance by enabling a label-free, simultaneous monitoring of structural changes at the cellular and molecular levels. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Giardiasis)
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Review

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25 pages, 15407 KiB  
Review
Ultrastructural Alterations of the Human Pathogen Giardia intestinalis after Drug Treatment
by Marlene Benchimol, Ana Paula Gadelha and Wanderley de Souza
Pathogens 2023, 12(6), 810; https://doi.org/10.3390/pathogens12060810 - 7 Jun 2023
Cited by 1 | Viewed by 2706
Abstract
This review presents the main cell characteristics altered after in vitro incubation of the parasite with commercial drugs used to treat the disease caused by Giardia intestinalis. This important intestinal parasite primarily causes diarrhea in children. Metronidazole and albendazole are the primary [...] Read more.
This review presents the main cell characteristics altered after in vitro incubation of the parasite with commercial drugs used to treat the disease caused by Giardia intestinalis. This important intestinal parasite primarily causes diarrhea in children. Metronidazole and albendazole are the primary compounds used in therapy against Giardia intestinalis. However, they provoke significant side effects, and some strains have developed resistance to metronidazole. Benzimidazole carbamates, such as albendazole and mebendazole, have shown the best activity against Giardia. Despite their in vitro efficacy, clinical treatment with benzimidazoles has yielded conflicting results, demonstrating lower cure rates. Recently, nitazoxanide has been suggested as an alternative to these drugs. Therefore, to enhance the quality of chemotherapy against this parasite, it is important to invest in developing other compounds that can interfere with key steps of metabolic pathways or cell structures and organelles. For example, Giardia exhibits a unique cell structure called the ventral disc, which is crucial for host adhesion and pathogenicity. Thus, drugs that can disrupt the adhesion process hold promise for future therapy against Giardia. Additionally, this review discusses new drugs and strategies that can be employed, as well as suggestions for developing novel drugs to control the infection caused by this parasite. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Giardiasis)
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