scholarly journals Serpin functions in host-pathogen interactions

2018 ◽  
Author(s):  
Jialing Bao ◽  
Guoqing Pan ◽  
Mortimer Poncz ◽  
Junhong Wei ◽  
Maoshuang Ran ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Cysteine Proteases ◽  
Future Research ◽  
Host Pathogen Interactions ◽  
Defense Proteins ◽  
Pathogenic Factors ◽  
Therapeutic Value ◽  
Host Pathogen ◽  
Infection And Inflammation ◽  
Novel Target

Serpins are a broadly distributed superfamily of protease inhibitors that are present in all kingdoms of life. The acronym, serpin, is derived from their function as potent ser ine p roteases in hibitors. Early studies of serpins focused on their functions in haemostasis since modulating serine proteases activities are essential for coagulation. Additional research has revealed that serpins function in infection and inflammation, by modulating serine and cysteine proteases activities. The aim of this review is to summarize the accumulating findings and current understanding of the functions of serpins in host-pathogen interactions, serving as host defense proteins as well as pathogenic factors. We also discuss the potential crosstalk between host and pathogen serpins. We anticipate that future research will elucidate the therapeutic value of this novel target.

scholarly journals Serpin functions in host-pathogen interactions

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4557 ◽  
Author(s):  
Jialing Bao ◽  
Guoqing Pan ◽  
Mortimer Poncz ◽  
Junhong Wei ◽  
Maoshuang Ran ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Cysteine Proteases ◽  
Future Research ◽  
Host Pathogen Interactions ◽  
Defense Proteins ◽  
Pathogenic Factors ◽  
Therapeutic Value ◽  
Host Pathogen ◽  
Infection And Inflammation ◽  
Novel Target

Serpins are a broadly distributed superfamily of protease inhibitors that are present in all kingdoms of life. The acronym, serpin, is derived from their function as potentserineproteasesinhibitors. Early studies of serpins focused on their functions in haemostasis since modulating serine proteases activities are essential for coagulation. Additional research has revealed that serpins function in infection and inflammation, by modulating serine and cysteine proteases activities. The aim of this review is to summarize the accumulating findings and current understanding of the functions of serpins in host-pathogen interactions, serving as host defense proteins as well as pathogenic factors. We also discuss the potential crosstalk between host and pathogen serpins. We anticipate that future research will elucidate the therapeutic value of this novel target.

scholarly journals Serpin functions in host-pathogen interactions

2018 ◽  
Author(s):  
Jialing Bao ◽  
Guoqing Pan ◽  
Mortimer Poncz ◽  
Junhong Wei ◽  
Maoshuang Ran ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Cysteine Proteases ◽  
Future Research ◽  
Host Pathogen Interactions ◽  
Defense Proteins ◽  
Pathogenic Factors ◽  
Therapeutic Value ◽  
Host Pathogen ◽  
Infection And Inflammation ◽  
Novel Target

Serpins are a broadly distributed superfamily of protease inhibitors that are present in all kingdoms of life. The acronym, serpin, is derived from their function as potent ser ine p roteases in hibitors. Early studies of serpins focused on their functions in haemostasis since modulating serine proteases activities are essential for coagulation. Additional research has revealed that serpins function in infection and inflammation, by modulating serine and cysteine proteases activities. The aim of this review is to summarize the accumulating findings and current understanding of the functions of serpins in host-pathogen interactions, serving as host defense proteins as well as pathogenic factors. We also discuss the potential crosstalk between host and pathogen serpins. We anticipate that future research will elucidate the therapeutic value of this novel target.

scholarly journals The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

2019 ◽  
Author(s):  
Feifei Xu ◽  
Alejandro Jiménez-González ◽  
Elin Einarsson ◽  
Ásgeir Ástvaldsson ◽  
Dimitra Peirasmaki ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Virulence Factors ◽  
Lateral Gene Transfer ◽  
Cysteine Proteases ◽  
Surface Antigens ◽  
Giardia Intestinalis ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
Giardia Muris

AbstractDiplomonad parasites of the genus Giardia have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic Giardia species, Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for other Giardia species. Comparative data would be particularly valuable for Giardia muris, which colonizes mice and is commonly used as a prototypic in vivo model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of G. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. G. muris and G. intestinalis share many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different to G. intestinalis, G. muris maintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from the G. muris genome suggest significant metabolic differences to G. intestinalis. Additionally, G. muris encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the Giardia genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the Giardia genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host-pathogen interaction in the G. muris – mouse pathosystem.Author summaryThe Giardia genus comprises eukaryotic single-celled parasites that infect many animals. The Giardia intestinalis species complex, which can colonize and cause diarrheal disease in humans and different animal hosts has been extensively explored at the genomic and cell biologic levels. Other Giardia species, such as the mouse parasite Giardia muris, have remained uncharacterized at the genomic level, hampering our understanding of in vivo host-pathogen interactions and the impact of host dependence on the evolution of the Giardia genus. We discovered that the G. muris genome encodes many of the same virulence factors as G. intestinalis. The G. muris genome has undergone genome contraction, potentially in response to a more defined infective niche in the murine host. We describe differences in metabolic and microbiome modulatory gene repertoire, mediated mainly by lateral gene transfer, that could be important for understanding infective success across the Giardia genus. Our findings provide new insights for the use of G. muris as a powerful model for exploring host-pathogen interactions in giardiasis.

Spatiotemporal Structure of Host-Pathogen Interactions in a Metapopulation

2009 ◽  
Vol 174 (3) ◽  
pp. 308
Author(s):  
Soubeyrand ◽  
Laine ◽  
Hanski ◽  
Penttinen
Keyword(s):  
Host Pathogen Interactions ◽  
Spatiotemporal Structure ◽  
Host Pathogen

scholarly journals Knowledge Gaps in Understanding the Etiology of Anemia in Indonesian Adolescents

2021 ◽  
Vol 42 (1_suppl) ◽  
pp. S39-S58
Author(s):  
Kesso Gabrielle van Zutphen ◽  
Klaus Kraemer ◽  
Alida Melse-Boonstra
Keyword(s):  
Current Knowledge ◽  
Vitamin A Deficiency ◽  
Public Health Problem ◽  
Population Group ◽  
Future Research ◽  
Folic Acid Deficiency ◽  
Knowledge Gaps ◽  
Local Conditions ◽  
Etiological Factors ◽  
Infection And Inflammation

Background: Anemia is a public health problem among adolescents in Indonesia. Strategies to prevent or treat anemia should be tailored to local conditions, taking into account its specific etiology and prevalence in a given setting and population group. Objective: This review aims to (1) identify and synthesize the current knowledge on the etiology of anemia among adolescents in Indonesia, (2) reveal knowledge gaps in this area, and (3) suggest directions for future research and programmatic work. Methods: We systematically searched PubMed, Web of Science, Scopus, Medline, and WorldCat databases for peer-reviewed journal articles to identify which etiological factors were related to anemia among Indonesian adolescents. Research papers were reviewed and included in the review according to inclusion criteria. Results: Of 13 studies, 8 showed that anemia was associated with iron deficiency; 4 are suggestive of vitamin A deficiency; and 2 of folic acid deficiency. Five studies underscore different etiological determinants for anemia, such as malaria, protein and energy malnutrition, vitamin B2 deficiency, calcium, and vitamin C deficiency. Based on these findings, we developed a framework on knowledge gaps on the etiology of anemia among adolescents in Indonesia, divided in 3 levels of knowledge: (1) significant knowledge gaps, (2) knowledge gaps, and (3) established knowledge. Conclusions: The knowledge gaps around the etiology of anemia among Indonesian adolescents are significant. Our framework emphasizes the need for further research across all etiological factors, namely inadequate nutritional intake and absorption, genetic hemoglobin disorders, infection and inflammation, and menstrual disorders.

scholarly journals Porcine small intestinal organoids as a model to explore ETEC–host interactions in the gut

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Bjarne Vermeire ◽  
Liara M. Gonzalez ◽  
Robert J. J. Jansens ◽  
Eric Cox ◽  
Bert Devriendt
Keyword(s):  
Intestinal Epithelial ◽  
Gut Health ◽  
Functional Responses ◽  
Host Pathogen Interactions ◽  
Epithelial Surface ◽  
Host Interactions ◽  
Intestinal Organoids ◽  
Host Pathogen ◽  
Small Intestinal

AbstractSmall intestinal organoids, or enteroids, represent a valuable model to study host–pathogen interactions at the intestinal epithelial surface. Much research has been done on murine and human enteroids, however only a handful studies evaluated the development of enteroids in other species. Porcine enteroid cultures have been described, but little is known about their functional responses to specific pathogens or their associated virulence factors. Here, we report that porcine enteroids respond in a similar manner as in vivo gut tissues to enterotoxins derived from enterotoxigenic Escherichia coli, an enteric pathogen causing postweaning diarrhoea in piglets. Upon enterotoxin stimulation, these enteroids not only display a dysregulated electrolyte and water balance as shown by their swelling, but also secrete inflammation markers. Porcine enteroids grown as a 2D-monolayer supported the adhesion of an F4+ ETEC strain. Hence, these enteroids closely mimic in vivo intestinal epithelial responses to gut pathogens and are a promising model to study host–pathogen interactions in the pig gut. Insights obtained with this model might accelerate the design of veterinary therapeutics aimed at improving gut health.

scholarly journals Reversed Proteolysis—Proteases as Peptide Ligases

Catalysts ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Peter Goettig
Keyword(s):  
Serine Proteases ◽  
Academic Research ◽  
Building Blocks ◽  
Peptide Bond ◽  
Cysteine Proteases ◽  
Small Peptides ◽  
Natural Peptide ◽  
Peptide Esters ◽  
Natural Amino Acids

Historically, ligase activity by proteases was theoretically derived due to their catalyst nature, and it was experimentally observed as early as around 1900. Initially, the digestive proteases, such as pepsin, chymotrypsin, and trypsin were employed to perform in vitro syntheses of small peptides. Protease-catalyzed ligation is more efficient than peptide bond hydrolysis in organic solvents, representing control of the thermodynamic equilibrium. Peptide esters readily form acyl intermediates with serine and cysteine proteases, followed by peptide bond synthesis at the N-terminus of another residue. This type of reaction is under kinetic control, favoring aminolysis over hydrolysis. Although only a few natural peptide ligases are known, such as ubiquitin ligases, sortases, and legumains, the principle of proteases as general catalysts could be adapted to engineer some proteases accordingly. In particular, the serine proteases subtilisin and trypsin were converted to efficient ligases, which are known as subtiligase and trypsiligase. Together with sortases and legumains, they turned out to be very useful in linking peptides and proteins with a great variety of molecules, including biomarkers, sugars or building blocks with non-natural amino acids. Thus, these engineered enzymes are a promising branch for academic research and for pharmaceutical progress.

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