Enzymes Involved in Pyrophosphate and Calcium Metabolism as Targets for Anti‐scuticociliate Chemotherapy

Mallo, Natalia; Lamas, Jesús; Defelipe, Ana-Paula; Sueiro, Rosa Ana; Fontenla, Francisco; Leiro, José-Manuel

doi:10.1111/jeu.12294

Cited by 6 publications

(4 citation statements)

References 78 publications

(76 reference statements)

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“…Even here, however, intervention can expedite the experimental program; methods for cloning sporocysts and re-inoculating parasite material into naive snails allow long-term propagation of especially valuable genetic lines [30]. Already, in vitro methods for the species are well-established, a freezing storage protocol is available [31], the metabolism is being unravelled [32] and drug screens are routine [33].…”

Section: In Vitro Culturesmentioning

confidence: 99%

Aquatic Parasite Cultures and Their Applications

Hutson

Cable

Grutter

et al. 2018

Trends in Parasitology

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In this era of unprecedented growth in aquaculture and trade, aquatic parasite cultures are essential to better understand emerging diseases and their implications for human and animal health. Yet culturing parasites presents multiple challenges, arising from their complex, often multi-host life cycles, multiple developmental stages, variable generation times and reproductive modes. Furthermore, the essential environmental requirements of most parasites remain enigmatic. Despite these inherent difficulties, in vivo and in vitro cultures are being developed for a small but growing number of aquatic pathogens. Expanding this resource will facilitate diagnostic capabilities and treatment trials, thus supporting the growth of sustainable aquatic commodities and communities. Aquatic parasite cultures permit advances in human, animal and environmental health Parasite cultures (see Glossary) facilitate the completion of life cycles over successive generations, either in vivo (i.e. on or in a host) or in vitro (i.e. in the absence of the host). Alternatively, if the full life cycle cannot be completed, some parasite development or extension of life span might be achieved. Ideally, cultures should have defined origins and depending on the application, it may be desirable for them to be genetically restricted and maintain the same restricted subset of genotypes across generations. The ultimate goal of a parasite culture is to provide readily manipulated material of defined life-stages for replicable experimental research. Aquatic cultures include the use of molluscan, crustacean, fish, amphibian, avian and mammalian hosts for a wide diversity of parasites (Table 1). Recent rapid growth in the mass production of aquatic animals for food, alongside growth in international trade, rapid domestication and application of new technologies, drive

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Section: In Vitro Culturesmentioning

confidence: 99%

Aquatic Parasite Cultures and Their Applications

Hutson

Cable

Grutter

et al. 2018

Trends in Parasitology

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“…Regulation of the intracellular pH of these compartments may represent a new target for development of chemotherapeutic treatments against scuticociliatosis (Mallo et al, 2016b). This has already been done in other parasites e.g.…”

Section: Discussionmentioning

confidence: 98%

Role of H+-pyrophosphatase activity in the regulation of intracellular pH in a scuticociliate parasite of turbot: Physiological effects

Mallo

Lamas

Felipe

et al. 2016

Experimental Parasitology

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The scuticociliatosis is a very serious disease that affects the cultured turbot, and whose causal agent is the anphizoic and marine euryhaline ciliate Philasterides dicentrarchi. Several protozoans possess acidic organelles that contain high concentrations of pyrophosphate (PPi), Ca(2+) and other elements with essential roles in vesicular trafficking, pH homeostasis and osmoregulation. P. dicentrarchi possesses a pyrophosphatase (H(+)-PPase) that pumps H(+) through the membranes of vacuolar and alveolar sacs. These compartments share common features with the acidocalcisomes described in other parasitic protozoa (e.g. acid content and Ca(2+) storage). We evaluated the effects of Ca(2+) and ATP on H (+)-PPase activity in this ciliate and analyzed their role in maintaining intracellular pH homeostasis and osmoregulation, by the addition of PPi and inorganic molecules that affect osmolarity. Addition of PPi led to acidification of the intracellular compartments, while the addition of ATP, CaCl2 and bisphosphonates analogous of PPi and Ca(2+) metabolism regulators led to alkalinization and a decrease in H(+)-PPase expression in trophozoites. Addition of NaCl led to proton release, intracellular Ca(2+) accumulation and downregulation of H(+)-PPase expression. We conclude that the regulation of the acidification of intracellular compartments may be essential for maintaining the intracellular pH homeostasis necessary for survival of ciliates and their adaptation to salt stress, which they will presumably face during the endoparasitic phase, in which the salinity levels are lower than in their natural environment.

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“…is one of the main pathogens affecting turbot culture and usually is associated with high mortality rates and important economic losses. Neither chemotherapeutic treatments nor vaccines have provided successful results against this ciliate to date[53]. To solve this issue, important efforts have been undertaken in recent years to gain a better understanding of host-pathogen interactions and to search for effector molecules and attempt to enhance their action[30,[54][55][56].…”

mentioning

confidence: 99%

Turbot (Scophthalmus maximus) Nk-Lysin induces protection against the pathogenic parasite Philasterides dicentrarchi via membrane disruption

Lama

Pereiro

Costa

et al. 2019

Fish & Shellfish Immunology

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P. dicentrarchi is one of the most threatening pathogens for turbot aquaculture. This protozoan ciliate is a causative agent of scuticociliatosis, which is a disease with important economic consequences for the sector. Neither vaccines nor therapeutic treatments are commercially available to combat this infection. Numerous antimicrobial peptides (AMPs) have demonstrated broad-spectrum activity against bacteria, viruses, fungi, parasites and even tumor cells; an example is Nk-lysin (Nkl), which is an AMP belonging to the saposin-like protein (SAPLIP) family with an ability to interact with biological membranes. Following the recent characterization of turbot Nkl, an expression plasmid encoding Nkl was constructed and an anti-Nkl polyclonal antibody was successfully tested. Using these tools, we demonstrated that although infection did not clearly affect nkl mRNA expression, it induced changes at the protein level. Turbot Nkl had the ability to inhibit proliferation of the P. dicentrarchi parasite both in vivo and in vitro. Moreover, a shortened peptide containing the active core of turbot Nkl (Nkl71-100) was synthesized and showed high antiparasitic activity with a direct effect on parasite viability that probably occurred via membrane disruption. Therefore, the nkl gene may be a good candidate for genetic breeding selection of fish, and either the encoded peptide or its shortened analog is a promising antiparasitic treatment in aquaculture.

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Enzymes Involved in Pyrophosphate and Calcium Metabolism as Targets for Anti‐scuticociliate Chemotherapy

Cited by 6 publications

References 78 publications

Aquatic Parasite Cultures and Their Applications

Aquatic Parasite Cultures and Their Applications

Role of H+-pyrophosphatase activity in the regulation of intracellular pH in a scuticociliate parasite of turbot: Physiological effects

Turbot (Scophthalmus maximus) Nk-Lysin induces protection against the pathogenic parasite Philasterides dicentrarchi via membrane disruption

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