scholarly journals Comprehensive analysis of human hookworm secreted proteins using a proteogenomic approach

2018 ◽  
Author(s):  
J Logan ◽  
SS Manda ◽  
YJ Choi ◽  
M Field ◽  
RM Eichenberger ◽  
...  

SummaryThe human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a number of animal hookworm species, but until now, the difficulty in obtaining sufficient live N. americanus has been an obstacle in characterizing the secretome of this important human pathogen. Herein we describe the ES proteome of N. americanus and utilize this information to conduct the first proteogenomic analysis of a parasitic helminth, significantly improving the available genome and thereby generating a robust description of the parasite secretome. The genome annotation resulted in a a revised prediction of 3,425 fewer genes than initially reported, accompanied by a significant increase in the number of exons and introns, total gene length and the percentage of the genome covered by genes. Almost 200 ES proteins were identified by LC-MS/MS with SCP/TAPS proteins, ‘hypothetical’ proteins and proteases among the most abundant families. These proteins were compared to commonly used model species of human parasitic infections, including Ancylostoma caninum, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. Our findings provide valuable information on important families of proteins with both known and unknown functions that could be instrumental in host-parasite interactions, including protein families that might be key for parasite survival in the onslaught of robust immune responses, as well as vaccine and drug targets.

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4510
Author(s):  
Dhanasekaran Sakthivel ◽  
Jaclyn Swan ◽  
Sarah Preston ◽  
MD Shakif-Azam ◽  
Pierre Faou ◽  
...  

Haemonchus contortusis the most pathogenic nematode of small ruminants. Infection in sheep and goats results in anaemia that decreases animal productivity and can ultimately cause death. The involvement of ruminant-specific galectin-11 (LGALS-11) and galectin-14 (LGALS-14) has been postulated to play important roles in protective immune responses against parasitic infection; however, their ligands are unknown. In the current study, LGALS-11 and LGALS-14 ligands inH. contortuswere identified from larval (L4) and adult parasitic stages extracts using immobilised LGALS-11 and LGALS-14 affinity column chromatography and mass spectrometry. Both LGALS-11 and LGALS-14 bound more putative protein targets in the adult stage ofH. contortus(43 proteins) when compared to the larval stage (two proteins). Of the 43 proteins identified in the adult stage, 34 and 35 proteins were bound by LGALS-11 and LGALS-14, respectively, with 26 proteins binding to both galectins. Interestingly, hematophagous stage-specific sperm-coating protein and zinc metalloprotease (M13), which are known vaccine candidates, were identified as putative ligands of both LGALS-11 and LGALS-14. The identification of glycoproteins ofH. contortusby LGALS-11 and LGALS-14 provide new insights into host-parasite interactions and the potential for developing new interventions.


2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Justyna Bień ◽  
Rusłan Sałamatin ◽  
Anna Sulima ◽  
Kirsi Savijoki ◽  
David Bruce Conn ◽  
...  

Abstractis an important model species in studies of therapeutics, biochemical processes, immune responses and other aspects of cestodiasis. The parasite produces numerous excretory-secretory (E-S) proteins and a glycocalyx covering its body. Our study focused on the mass spectrometry analysis of the E-S material with an objective to determine if E-S contains any new proteins, in particular those that can be identified as: antigens, vaccine candidates and drug targets. These proteins might engage directly in host-parasite interactions. Adult parasites collected from experimentally infected rats were cultured


Parasitology ◽  
2019 ◽  
Vol 146 (10) ◽  
pp. 1217-1232
Author(s):  
Carolina De Marco Veríssimo ◽  
Carlos Graeff-Teixeira ◽  
Malcolm K. Jones ◽  
Alessandra L. Morassutti

AbstractThe investigation of the glycan repertoire of several organisms has revealed a wide variation in terms of structures and abundance of glycan moieties. Among the parasites, it is possible to observe different sets of glycoconjugates across taxa and developmental stages within a species. The presence of distinct glycoconjugates throughout the life cycle of a parasite could relate to the ability of that organism to adapt and survive in different hosts and environments. Carbohydrates on the surface, and in excretory-secretory products of parasites, play essential roles in host–parasite interactions. Carbohydrate portions of complex molecules of parasites stimulate and modulate host immune responses, mainly through interactions with specific receptors on the surface of dendritic cells, leading to the generation of a pattern of response that may benefit parasite survival. Available data reviewed here also show the frequent aspect of parasite immunomodulation of mammalian responses through specific glycan interactions, which ultimately makes these molecules promising in the fields of diagnostics and vaccinology.


Parasitology ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 411-424 ◽  
Author(s):  
I. BARBER ◽  
J. P. SCHARSACK

SUMMARYPlerocercoids of the pseudophyllidean cestodeSchistocephalus solidusinfect the three-spined sticklebackGasterosteus aculeatus, with important consequences for the biology of host fish. Techniques for culturing the parasitein vitroand generating infective stages that can be used to infect sticklebacks experimentally have been developed, and the system is increasingly used as a laboratory model for investigating aspects of host-parasite interactions. Recent experimental laboratory studies have focused on the immune responses of hosts to infection, the consequences of infection for the growth and reproductive development of host fish and the effects of infection on host behaviour. Here we introduce the host and the parasite, review the major findings of these recent experimental infection studies and identify further aspects of host parasite interactions that might be investigated using the system.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Marta T. Gomes ◽  
Angela H. Lopes ◽  
José Roberto Meyer-Fernandes

The interaction and survival of pathogens in hostile environments and in confrontation with host immune responses are important mechanisms for the establishment of infection. Ectophosphatases are enzymes localized at the plasma membrane of cells, and their active sites face the external medium rather than the cytoplasm. Once activated, these enzymes are able to hydrolyze phosphorylated substrates in the extracellular milieu. Several studies demonstrated the presence of surface-located ecto-phosphatases in a vast number of pathogenic organisms, including bacteria, protozoa, and fungi. Little is known about the role of ecto-phosphatases in host-pathogen interactions. The present paper provides an overview of recent findings related to the virulence induced by these surface molecules in protozoa and fungi.


2017 ◽  
Author(s):  
Dhanasekaran Sakthivel ◽  
Jaclyn Swan ◽  
Sarah Preston ◽  
MD Shakif-Azam ◽  
Pierre Faou ◽  
...  

Haemonchus contortus is the most pathogenic nematode of small ruminants. Infection in sheep and goats results in anaemia that decreases animal productivity and can ultimately cause death. The involvement of ruminant-specific galectin-11 (LGALS-11) and galectin-14 (LGALS-14) has been postulated to play important roles in protective immune responses against parasitic infection; however, their ligands are unknown. In the current study, LGALS-11 and LGALS-14 ligands in H. contortus were identified from larval (L4) and adult parasitic stages extracts using immobilised LGALS-11 and LGALS-14 affinity column chromatography and mass spectrometry. Both LGALS-11 and LGALS-14 bound more putative protein targets in the adult stage of H. contortus (43 proteins) when compared to the larval stage (2 proteins). Of the 43 proteins identified in the adult stage, 34 and 35 proteins were bound by LGALS-11 and LGALS-14, respectively, with 26 proteins binding to both galectins. Interestingly, hematophagous stage-specific sperm-coating protein and zinc metalloprotease (M13), which are known vaccine candidates, were identified as putative ligands of both LGALS-11 and LGALS-14. The identification of glycoproteins of H. contortus by LGALS-11 and LGALS-14 provide new insights into host-parasite interactions and the potential for developing new interventions.


2016 ◽  
Vol 12 (12) ◽  
pp. 20160839 ◽  
Author(s):  
Laura Gangoso ◽  
Rafael Gutiérrez-López ◽  
Josué Martínez-de la Puente ◽  
Jordi Figuerola

Individual genetic diversity is predicted to influence host–parasite interactions. Together with the genes directly associated with immune responses, variation in genes regulating vertebrate melanin-based pigmentation may play an important role in these interactions, mainly through the pleiotropic effects that affect colour-specific physiology, behaviour and immunity. Here, we test the hypothesis that the prevalence of avian malarial parasites differs between phenotypes in a raptor species in which the genetic basis of colour polymorphism and its pleiotropic effects over immune functions are known. We found that dark morphs had a higher prevalence of Plasmodium parasites than pale ones but detected no such association for Haemoproteus . This pattern may be associated with unequal exposure to vectors or, as suggested by our circumstantial evidence, to a differential ability to mount an immune response against blood parasites.


2005 ◽  
Vol 83 (4) ◽  
pp. 610-619 ◽  
Author(s):  
M E Scott ◽  
O K Dare ◽  
T Tu ◽  
K G Koski

Energy restriction reduces Heligmosomoides polygyrus (Dujardin, 1845) (Nematoda) infection by reducing transmission-related behaviours but prolongs parasite survival by suppressing immune responses in individually housed mice. To determine the relative importance of these two processes in accumulation of worms in mouse populations, 10 female CD1 mice were housed in each of eight indoor arenas with ad libitum access to either an energy-sufficient (ES) diet or an energy-restricted (ER) diet with 20% less metabolizable energy (four arenas per diet). After 3 weeks, H. polygyrus transmission was initiated by introducing larvae onto damp peat trays. Mice adapted to the ER diet through increased food intake and nesting and reduced overall activity; after 6 weeks, nutritional and immunological measures were comparable between diet groups. With continuing exposure to parasite larvae, mice in both ER and ES arenas developed resistance to the incoming larvae; however, mice in the ER arenas accumulated lower worm burdens than mice in the ES arenas despite their increased contact with peat. We suggest that the comparable immunocompetence of mice in the ER and ES arenas enabled the ER mice exposed to higher transmission rates to more rapidly reject the parasites, leading to lower final worm numbers, a pattern frequently observed in other helminth infections.


2011 ◽  
Vol 51 ◽  
pp. 161-175 ◽  
Author(s):  
Christopher M. Ryan ◽  
Natalia de Miguel ◽  
Patricia J. Johnson

Trichomonas vaginalis is a sexually transmitted obligate extracellular parasite that colonizes the human urogenital tract. Despite being of critical importance to the parasite's survival relatively little is known about the mechanisms employed by T. vaginalis to establish an infection and thrive within its host. Several studies have focused on the interaction of the parasite with host cells and extracellular matrix, identifying multiple suspected T. vaginalis adhesins. However, with the exception of its surface lipophosphoglycan, the evidence supporting a role in adhesion is indirect or controversial for many candidate molecules. The availability of the T. vaginalis genome sequence paved the way for genomic analyses to search for proteins possibly involved in host–parasite interactions. Several proteomic analyses have also provided insight into surface, soluble and secreted proteins that may be involved in Trichomonas pathogenesis. Although the accumulation of molecular data allows for a more rational approach towards identifying drug targets and vaccine candidates for this medically important parasite, a continued effort is required to advance our understanding of its biology. In the present chapter, we review the current status of research aimed at understanding T. vaginalis pathogenesis. Applied experimental approaches, an overview of significant conclusions drawn from this research and future challenges are discussed.


Author(s):  
Joshua Seun Olajide ◽  
Bolatito Olopade ◽  
Jianping Cai

RNAs are a class of molecules and the majority in eukaryotes are arbitrarily termed non- coding transcripts which are broadly classified as short and long non-coding RNAs. Recently, knowledge of the identification and functions of long non-coding RNAs have continued to accumulate and they are being recognized as important molecules that regulate parasite-host interface, parasite differentiation, host responses, and disease progression. Herein, we present and integrate the functions of host and parasite long non-coding RNAs during infections within the context of epigenetic re-programming and molecular crosstalk in the course of host-parasite interactions. Also, the modular range of parasite and host long non-coding RNAs in coordinated parasite developmental changes and host immune dynamic landscapes are discussed. We equally canvass the prospects of long non-coding RNAs in disease diagnosis and prognosis. Hindsight and suggestions are offered with the aim that it will bolster our understanding for future works on host and parasite long non-coding RNAs.


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