scholarly journals Effector prediction and characterization in the oomycete pathogen Bremia lactucae reveal host-recognized WY domain proteins that lack the canonical RXLR motif

2019 ◽  
Author(s):  
Kelsey Wood ◽  
Munir Nur ◽  
Juliana Gil ◽  
Kyle Fletcher ◽  
Kim Lakeman ◽  
...  
Keyword(s):  
Immune System ◽  
Downy Mildew ◽  
Plant Pathogens ◽  
Domain Architecture ◽  
Host Cells ◽  
Evolutionary Divergence ◽  
Host Immune System ◽  
Bremia Lactucae ◽  
Structural Element ◽  
Lettuce Downy Mildew

AbstractPathogens infecting plants and animals use a diverse arsenal of effector proteins to suppress the host immune system and promote infection. Identification of effectors in pathogen genomes is foundational to understanding mechanisms of pathogenesis, for monitoring field pathogen populations, and for breeding disease resistance. We identified candidate effectors from the lettuce downy mildew pathogen, Bremia lactucae, using comparative genomics and bioinformatics to search for the WY domain. This conserved structural element is found in Phytophthora effectors and some other oomycete pathogens; it has been implicated in the immune-suppressing function of these effectors as well as their recognition by host resistance proteins. We predicted 54 WY domain containing proteins in isolate SF5 of B. lactucae that have substantial variation in both sequence and domain architecture. These candidate effectors exhibit several characteristics of pathogen effectors, including an N-terminal signal peptide, lineage specificity, and expression during infection. Unexpectedly, only a minority of B. lactucae WY effectors contain the canonical N-terminal RXLR motif, which is a conserved feature in the majority of cytoplasmic effectors reported in Phytophthora spp. Functional analysis effectors containing WY domains revealed eleven out of 21 that triggered necrosis, which is characteristic of the immune response on wild accessions and domesticated lettuce lines containing resistance genes. Only two of the eleven recognized effectors contained a canonical RXLR motif, suggesting that there has been an evolutionary divergence in sequence motifs between genera; this has major consequences for robust effector prediction in oomycete pathogens.Author SummaryThere is a microscopic battle that takes place at the molecular level during infection of plants and animals by pathogens. Some of the weapons that pathogens battle with are known as “effectors,” which are secreted proteins that enter host cells to alter physiology and suppress the immune system. Effectors can also be a liability for plant pathogens because plants have evolved ways to recognize these effectors, triggering a defense response leading to localized cell death, which prevents the spread of the pathogen. Here we used computer models to predict effectors from the genome of Bremia lactucae, the causal agent of lettuce downy mildew. Three effectors were demonstrated to suppress the basal immune system of lettuce. Eleven effectors were recognized by one or more resistant lines of lettuce. In addition to contributing to our understanding of the mechanisms of pathogenesis, this study of effectors is useful for breeding disease resistant lettuce, decreasing agricultural reliance on fungicides.

scholarly journals Effector prediction and characterization in the oomycete pathogen Bremia lactucae reveal host-recognized WY domain proteins that lack the canonical RXLR motif

2020 ◽  
Vol 16 (10) ◽  
pp. e1009012
Author(s):  
Kelsey J. Wood ◽  
Munir Nur ◽  
Juliana Gil ◽  
Kyle Fletcher ◽  
Kim Lakeman ◽  
...  
Keyword(s):  
Immune System ◽  
Domain Architecture ◽  
Effector Proteins ◽  
Evolutionary Divergence ◽  
Host Immune System ◽  
Sequence Motifs ◽  
Bremia Lactucae ◽  
Pathogen Effectors ◽  
Lineage Specificity ◽  
Pathogen Populations

Pathogens that infect plants and animals use a diverse arsenal of effector proteins to suppress the host immune system and promote infection. Identification of effectors in pathogen genomes is foundational to understanding mechanisms of pathogenesis, for monitoring field pathogen populations, and for breeding disease resistance. We identified candidate effectors from the lettuce downy mildew pathogen Bremia lactucae by searching the predicted proteome for the WY domain, a structural fold found in effectors that has been implicated in immune suppression as well as effector recognition by host resistance proteins. We predicted 55 WY domain containing proteins in the genome of B. lactucae and found substantial variation in both sequence and domain architecture. These candidate effectors exhibit several characteristics of pathogen effectors, including an N-terminal signal peptide, lineage specificity, and expression during infection. Unexpectedly, only a minority of B. lactucae WY effectors contain the canonical N-terminal RXLR motif, which is a conserved feature in the majority of cytoplasmic effectors reported in Phytophthora spp. Functional analysis of 21 effectors containing WY domains revealed 11 that elicited cell death on wild accessions and domesticated lettuce lines containing resistance genes, indicative of recognition of these effectors by the host immune system. Only two of the 11 recognized effectors contained the canonical RXLR motif, suggesting that there has been an evolutionary divergence in sequence motifs between genera; this has major consequences for robust effector prediction in oomycete pathogens.

scholarly journals Leishmania donovani Secretory Mevalonate Kinase Regulates Host Immune Response and Facilitates Phagocytosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Tanvir Bamra ◽  
Taj Shafi ◽  
Sushmita Das ◽  
Manjay Kumar ◽  
Manas Ranjan Dikhit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Leishmania Donovani ◽  
Indian Subcontinent ◽  
Parasite Burden ◽  
Host Immune Response ◽  
Host Cells ◽  
Interleukin 4 ◽  
Host Immune System ◽  
Mevalonate Kinase

Summary StatementLeishmania secretes over 151 proteins during in vitro cultivation. Cellular functions of one such novel protein: mevalonate kinase is discussed here; signifying its importance in Leishmania infection.Visceral Leishmaniasis is a persistent infection, caused by Leishmania donovani in Indian subcontinent. This persistence is partly due to phagocytosis and evasion of host immune response. The underlying mechanism involves secretory proteins of Leishmania parasite; however, related studies are meagre. We have identified a novel secretory Leishmania donovani glycoprotein, Mevalonate kinase (MVK), and shown its importance in parasite internalization and immuno-modulation. In our studies, MVK was found to be secreted maximum after 1 h temperature stress at 37°C. Its secretion was increased by 6.5-fold in phagolysosome-like condition (pH ~5.5, 37°C) than at pH ~7.4 and 25°C. Treatment with MVK modulated host immune system by inducing interleukin-10 and interleukin-4 secretion, suppressing host’s ability to kill the parasite. Peripheral blood mononuclear cell (PBMC)-derived macrophages infected with mevalonate kinase-overexpressing parasites showed an increase in intracellular parasite burden in comparison to infection with vector control parasites. Mechanism behind the increase in phagocytosis and immunosuppression was found to be phosphorylation of mitogen-activated protein (MAP) kinase pathway protein, Extracellular signal-regulated kinases-1/2, and actin scaffold protein, cortactin. Thus, we conclude that Leishmania donovani Mevalonate kinase aids in parasite engulfment and subvert the immune system by interfering with signal transduction pathways in host cells, which causes suppression of the protective response and facilitates their persistence in the host. Our work elucidates the involvement of Leishmania in the process of phagocytosis which is thought to be dependent largely on macrophages and contributes towards better understanding of host pathogen interactions.

scholarly journals Host interactors of effector proteins of the lettuce downy mildew Bremia lactucae obtained by yeast two-hybrid screening

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0226540 ◽  
Author(s):  
Alexandra J. E. Pelgrom ◽  
Claudia-Nicole Meisrimler ◽  
Joyce Elberse ◽  
Thijs Koorman ◽  
Mike Boxem ◽  
...  
Keyword(s):  
Downy Mildew ◽  
Effector Proteins ◽  
Bremia Lactucae ◽  
Yeast Two Hybrid ◽  
Lettuce Downy Mildew ◽  
Two Hybrid ◽  
Hybrid Screening

scholarly journals Insensitivity to the Fungicide Fosetyl-Aluminum in California Isolates of the Lettuce Downy Mildew Pathogen, Bremia lactucae

Plant Disease ◽  
2004 ◽  
Vol 88 (5) ◽  
pp. 502-508 ◽  
Author(s):  
Sarah Brown ◽  
Steven T. Koike ◽  
Oswaldo E. Ochoa ◽  
Frank Laemmlen ◽  
Richard W. Michelmore
Keyword(s):  
Quantitative Analysis ◽  
Downy Mildew ◽  
Mating Type ◽  
Control Measures ◽  
Bremia Lactucae ◽  
Widespread Occurrence ◽  
Lettuce Downy Mildew ◽  
Normal Field ◽  
Growth Room ◽  
Disease Pressure

Lettuce downy mildew, caused by Bremia lactucae, is the most important foliar disease of lettuce in California. In recent years, there were apparent failures of fungicides containing fosetyl-aluminum (Aliette) to control downy mildew in commercial lettuce fields in California. Consequently, we characterized 134 isolates collected over 2 years from throughout the coastal growing areas of California for insensitivity to the fungicides fosetyl-aluminum and maneb, pathotype, and mating type. Tests using seedlings in controlled growth room conditions demonstrated the widespread occurrence of insensitivity to fosetyl-aluminum in California populations of B. lactucae. Fifty percent of the isolates assayed sporulated profusely in the presence of fosetyl-aluminum applied at rates twice the normal field dosage, and an additional 40% showed moderate sporulation at this rate. Fosetyl-aluminum-insensitive isolates were detected from all regions sampled. Insensitivity was also observed in multiple pathotypes. Insensitivity was not complete, however, because quantitative analysis of the number of lesions on older plants revealed that applications of fosetyl-aluminum could reduce the levels of disease by 50%. Therefore, while fosetyl-aluminum may have utility under low disease pressure in the field, other control measures are required to provide control under conditions favorable to the disease.

The Specific Virulence Characteristics of Bremia Lactucae (Lettuce Downy Mildew) in Australia.

1984 ◽  
Vol 13 (4) ◽  
pp. 58
Author(s):  
DS Trimboli ◽  
IR Crute
Keyword(s):  
Downy Mildew ◽  
Bremia Lactucae ◽  
Lettuce Downy Mildew ◽  
Specific Virulence

scholarly journals QTL Mapping of Intestinal Neutrophil Variation in Threespine Stickleback Reveals Possible Gene Targets Connecting Intestinal Inflammation and Systemic Health

2019 ◽  
Vol 10 (2) ◽  
pp. 613-622
Author(s):  
Emily A. Beck ◽  
Mark C. Currey ◽  
Clayton M. Small ◽  
William A. Cresko
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Intestinal Inflammation ◽  
Threespine Stickleback ◽  
Microbial Interactions ◽  
Host Cells ◽  
Host Immune System ◽  
Complex Genetics ◽  
Disease States ◽  
Host Genetic

Selection, via host immunity, is often required to foster beneficial microbial symbionts and suppress deleterious pathogens. In animals, the host immune system is at the center of this relationship. Failed host immune system-microbial interactions can result in a persistent inflammatory response in which the immune system indiscriminately attacks resident microbes, and at times the host cells themselves, leading to diseases such as Ulcerative Colitis, Crohn’s Disease, and Psoriasis. Host genetic variation has been linked to both microbiome diversity and to severity of such inflammatory disease states in humans. However, the microbiome and inflammatory states manifest as quantitative traits, which encompass many genes interacting with one another and the environment. The mechanistic relationships among all of these interacting components are still not clear. Developing natural genetic models of host-microbe interactions is therefore fundamental to understanding the complex genetics of these and other diseases. Threespine stickleback (Gasterosteus aculeatus) fish are a tractable model for attacking this problem because of abundant population-level genetic and phenotypic variation in the gut inflammatory response. Previous work in our laboratory identified genetically divergent stickleback populations exhibiting differences in intestinal neutrophil activity. We took advantage of this diversity to genetically map variation in an emblematic element of gut inflammation - intestinal neutrophil recruitment - using an F2-intercross mapping framework. We identified two regions of the genome associated with increased intestinal inflammation containing several promising candidate genes. Within these regions we found candidates in the Coagulation/Complement System, NFkB and MAPK pathways along with several genes associated with intestinal diseases and neurological diseases commonly accompanying intestinal inflammation as a secondary symptom. These findings highlight the utility of using naturally genetically diverse ‘evolutionary mutant models’ such as threespine stickleback to better understand interactions among host genetic diversity and microbiome variation in health and disease states.

scholarly journals Effector identification in the lettuce downy mildew Bremia lactucae by massively parallel transcriptome sequencing

2012 ◽  
Vol 13 (7) ◽  
pp. 719-731 ◽  
Author(s):  
JOOST H. M. STASSEN ◽  
MICHAEL F. SEIDL ◽  
PIM W. J. VERGEER ◽  
ISAÄC J. NIJMAN ◽  
BEREND SNEL ◽  
...  
Keyword(s):  
Downy Mildew ◽  
Transcriptome Sequencing ◽  
Massively Parallel ◽  
Bremia Lactucae ◽  
Lettuce Downy Mildew

scholarly journals Glycans in Virus-Host Interactions: A Structural Perspective

2021 ◽  
Vol 8 ◽  
Author(s):  
Nathaniel L. Miller ◽  
Thomas Clark ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Immune System ◽  
Host Cells ◽  
Host Immune System ◽  
Host Interactions ◽  
Viral Glycoproteins ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Anti Hiv ◽  
Structural Perspective

Many interactions between microbes and their hosts are driven or influenced by glycans, whose heterogeneous and difficult to characterize structures have led to an underappreciation of their role in these interactions compared to protein-based interactions. Glycans decorate microbe glycoproteins to enhance attachment and fusion to host cells, provide stability, and evade the host immune system. Yet, the host immune system may also target these glycans as glycoepitopes. In this review, we provide a structural perspective on the role of glycans in host-microbe interactions, focusing primarily on viral glycoproteins and their interactions with host adaptive immunity. In particular, we discuss a class of topological glycoepitopes and their interactions with topological mAbs, using the anti-HIV mAb 2G12 as the archetypical example. We further offer our view that structure-based glycan targeting strategies are ready for application to viruses beyond HIV, and present our perspective on future development in this area.

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