抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

基礎講座 電気泳動(Electrophoresis)

The recent rate of emergence of pathogenic fungi that are resistant to the limited number of commonly used antifungal agents is unprecedented. The azoles, for example, are used not only for human and animal health care and crop protection but also in antifouling coatings and timber preservation. The ubiquity and multiple uses of azoles have hastened the independent evolution of resistance in many environments. One consequence is an increasing risk in human health care from naturally occurring opportunistic fungal pathogens that have acquired resistance to this broad class of chemicals. To avoid a global collapse in our ability to control fungal infections and to avoid critical failures in medicine and food security, we must improve our stewardship of extant chemicals, promote new antifungal discovery, and leverage emerging technologies for alternative solutions.

/pdf/worldwide-emergence-of-resistance-to-antifungal-drugs-1jv9giyzbt.pdf

Worldwide emergence of resistance to antifungal drugs challenges human health and food security

Plants can be colonized by fungi that have adopted highly diverse lifestyles, ranging from symbiotic to necrotrophic. Colonization is governed in all systems by hundreds of secreted fungal effector molecules. These effectors suppress plant defense responses and modulate plant physiology to accommodate fungal invaders and provide them with nutrients. Fungal effectors either function in the interaction zone between the fungal hyphae and host or are transferred to plant cells. This review describes the effector repertoires of 84 plant-colonizing fungi. We focus on the mechanisms that allow these fungal effectors to promote virulence or compatibility, discuss common plant nodes that are targeted by effectors, and provide recent insights into effector evolution. In addition, we address the issue of effector uptake in plant cells and highlight open questions and future challenges.

Fungal Effectors and Plant Susceptibility

Botrytis cinerea, the causative agent of gray mold disease, is an aggressive fungal pathogen that infects more than 200 plant species. Here, we show that some B. cinerea small RNAs (Bc-sRNAs) can silence Arabidopsis and tomato genes involved in immunity. These Bc-sRNAs hijack the host RNA interference (RNAi) machinery by binding to Arabidopsis Argonaute 1 (AGO1) and selectively silencing host immunity genes. The Arabidopsis ago1 mutant exhibits reduced susceptibility to B. cinerea, and the B. cinerea dcl1 dcl2 double mutant that can no longer produce these Bc-sRNAs displays reduced pathogenicity on Arabidopsis and tomato. Thus, this fungal pathogen transfers “virulent” sRNA effectors into host plant cells to suppress host immunity and achieve infection, which demonstrates a naturally occurring cross-kingdom RNAi as an advanced virulence mechanism.

/pdf/fungal-small-rnas-suppress-plant-immunity-by-hijacking-host-4eq92r0ihp.pdf

Fungal Small RNAs Suppress Plant Immunity by Hijacking Host RNA Interference Pathways

Aggressive fungal pathogens such as Botrytis and Verticillium spp. cause severe crop losses worldwide. We recently discovered that Botrytis cinerea delivers small RNAs (Bc-sRNAs) into plant cells to silence host immunity genes. Such sRNA effectors are mostly produced by Botrytis cinerea Dicer-like protein 1 (Bc-DCL1) and Bc-DCL2. Here we show that expressing sRNAs that target Bc-DCL1 and Bc-DCL2 in Arabidopsis and tomato silences Bc-DCL genes and attenuates fungal pathogenicity and growth, exemplifying bidirectional cross-kingdom RNAi and sRNA trafficking between plants and fungi. This strategy can be adapted to simultaneously control multiple fungal diseases. We also show that Botrytis can take up external sRNAs and double-stranded RNAs (dsRNAs). Applying sRNAs or dsRNAs that target Botrytis DCL1 and DCL2 genes on the surface of fruits, vegetables and flowers significantly inhibits grey mould disease. Such pathogen gene-targeting RNAs represent a new generation of environmentally friendly fungicides.

/pdf/bidirectional-cross-kingdom-rnai-and-fungal-uptake-of-559u6ml7l7.pdf

Bidirectional cross-kingdom RNAi and fungal uptake of external RNAs confer plant protection

A never-ending arms race drives coevolution between pathogens and hosts. In plants, pathogen attacks invoke multiple layers of host immune responses. Many pathogens deliver effector proteins into host cells to suppress host immunity, and many plants have evolved resistance proteins to recognize effectors and trigger robust resistance. Here, we discuss findings on noncoding small RNAs (sRNAs) from plants and pathogens, which regulate host immunity and pathogen virulence. Recent discoveries have unveiled the role of noncoding sRNAs from eukaryotic pathogens and bacteria in pathogenicity in both plant and animal hosts. The discovery of fungal sRNAs that are delivered into host cells to suppress plant immunity added sRNAs to the list of pathogen effectors. Similar to protein effector genes, many of these sRNAs are generated from transposable element (TE) regions, which are likely to contribute to rapidly evolving virulence and host adaptation. We also discuss RNA silencing that occurs between organisms.

Small RNAs: A New Paradigm in Plant-Microbe Interactions

Pathogens secrete effector proteins to suppress host immune responses. Recently, we showed that an aggressive plant fungal pathogen Botrytis cinerea can also deliver small RNA effectors into host cells to suppress host immunity. B. cinerea sRNAs (Bc-sRNAs) translocate into host plants and hijack the plant RNAi machinery to induce cross-kingdom RNAi of host immune responsive genes. Here, we functionally characterized another Bc-sRNA effector Bc-siR37 that is predicted to target at least 15 Arabidopsis genes, including WRKY transcription factors, receptor-like kinases, and cell wall-modifying enzymes. Upon B. cinerea infection, the expression level of Bc-siR37 was induced, and at least eight predicted Arabidopsis target genes were downregulated. These target genes were also suppressed in the transgenic Arabidopsis plants overexpressing Bc-siR37, which exhibited enhanced disease susceptibility to B. cinerea. Furthermore, the knockout mutants of the Bc-siR37 targets, At-WRKY7, At-PMR6, and At-FEI2, also exhibited enhanced disease susceptibility to B. cinerea, giving further support that these genes indeed play a positive role in plant defense against B. cinerea. Our study demonstrates that analysis of pathogen sRNA effectors can be a useful tool to help identify host immunity genes against the corresponding pathogen.

https://www.tandfonline.com/doi/pdf/10.1080/15476286.2017.1291112

Botrytis small RNA Bc-siR37 suppresses plant defense genes by cross-kingdom RNAi.

http://www.gene-quantification.net/weiberg-et-al-small-rna-kingdom-communication-2015.pdf

Arne Weiberg

Papers

Fungal Small RNAs Suppress Plant Immunity by Hijacking Host RNA Interference Pathways

Bidirectional cross-kingdom RNAi and fungal uptake of external RNAs confer plant protection

Small RNAs: A New Paradigm in Plant-Microbe Interactions

Botrytis small RNA Bc-siR37 suppresses plant defense genes by cross-kingdom RNAi.

Conversations between kingdoms: small RNAs.