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1.
Lysin Motif (LysM) Proteins: Interlinking Manipulation of Plant Immunity and Fungi.
Hu, SP, Li, JJ, Dhar, N, Li, JP, Chen, JY, Jian, W, Dai, XF, Yang, XY
International journal of molecular sciences. 2021;(6)
Abstract
The proteins with lysin motif (LysM) are carbohydrate-binding protein modules that play a critical role in the host-pathogen interactions. The plant LysM proteins mostly function as pattern recognition receptors (PRRs) that sense chitin to induce the plant's immunity. In contrast, fungal LysM blocks chitin sensing or signaling to inhibit chitin-induced host immunity. In this review, we provide historical perspectives on plant and fungal LysMs to demonstrate how these proteins are involved in the regulation of plant's immune response by microbes. Plants employ LysM proteins to recognize fungal chitins that are then degraded by plant chitinases to induce immunity. In contrast, fungal pathogens recruit LysM proteins to protect their cell wall from hydrolysis by plant chitinase to prevent activation of chitin-induced immunity. Uncovering this coevolutionary arms race in which LysM plays a pivotal role in manipulating facilitates a greater understanding of the mechanisms governing plant-fungus interactions.
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2.
Exploiting Structural Modelling Tools to Explore Host-Translocated Effector Proteins.
Amoozadeh, S, Johnston, J, Meisrimler, CN
International journal of molecular sciences. 2021;(23)
Abstract
Oomycete and fungal interactions with plants can be neutral, symbiotic or pathogenic with different impact on plant health and fitness. Both fungi and oomycetes can generate so-called effector proteins in order to successfully colonize the host plant. These proteins modify stress pathways, developmental processes and the innate immune system to the microbes' benefit, with a very different outcome for the plant. Investigating the biological and functional roles of effectors during plant-microbe interactions are accessible through bioinformatics and experimental approaches. The next generation protein modeling software RoseTTafold and AlphaFold2 have made significant progress in defining the 3D-structure of proteins by utilizing novel machine-learning algorithms using amino acid sequences as their only input. As these two methods rely on super computers, Google Colabfold alternatives have received significant attention, making the approaches more accessible to users. Here, we focus on current structural biology, sequence motif and domain knowledge of effector proteins from filamentous microbes and discuss the broader use of novel modelling strategies, namely AlphaFold2 and RoseTTafold, in the field of effector biology. Finally, we compare the original programs and their Colab versions to assess current strengths, ease of access, limitations and future applications.
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3.
Recognition and defence of plant-infecting fungal pathogens.
Saur, IML, Hückelhoven, R
Journal of plant physiology. 2021;:153324
Abstract
Attempted infections of plants with fungi result in diverse outcomes ranging from symptom-less resistance to severe disease and even death of infected plants. The deleterious effect on crop yield have led to intense focus on the cellular and molecular mechanisms that explain the difference between resistance and susceptibility. This research has uncovered plant resistance or susceptibility genes that explain either dominant or recessive inheritance of plant resistance with many of them coding for receptors that recognize pathogen invasion. Approaches based on cell biology and phytochemistry have contributed to identifying factors that halt an invading fungal pathogen from further invasion into or between plant cells. Plant chemical defence compounds, antifungal proteins and structural reinforcement of cell walls appear to slow down fungal growth or even prevent fungal penetration in resistant plants. Additionally, the hypersensitive response, in which a few cells undergo a strong local immune reaction, including programmed cell death at the site of infection, stops in particular biotrophic fungi from spreading into surrounding tissue. In this review, we give a general overview of plant recognition and defence of fungal parasites tracing back to the early 20th century with a special focus on Triticeae and on the progress that was made in the last 30 years.
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4.
Versatile effectors of phytopathogenic fungi target host immunity.
Tariqjaveed, M, Mateen, A, Wang, S, Qiu, S, Zheng, X, Zhang, J, Bhadauria, V, Sun, W
Journal of integrative plant biology. 2021;(11):1856-1873
Abstract
Phytopathogenic fungi secrete a large arsenal of effector molecules, including proteinaceous effectors, small RNAs, phytohormones and derivatives thereof. The pathogenicity of fungal pathogens is primarily determined by these effectors that are secreted into host cells to undermine innate immunity, as well as to facilitate the acquisition of nutrients for their in planta growth and proliferation. After conventional and non-conventional secretion, fungal effectors are translocated into different subcellular compartments of the host cells to interfere with various biological processes. In extracellular spaces, apoplastic effectors cope with physical and chemical barriers to break the first line of plant defenses. Intracellular effectors target essential immune components on the plasma membrane, in the cytosol, including cytosolic organelles, and in the nucleus to suppress host immunity and reprogram host physiology, favoring pathogen colonization. In this review, we comprehensively summarize the recent advances in fungal effector biology, with a focus on the versatile virulence functions of fungal effectors in promoting pathogen infection and colonization. A perspective of future research on fungal effector biology is also discussed.
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5.
Fungal beta-glucans as adjuvants for treating cancer patients - A systematic review of clinical trials.
Steimbach, L, Borgmann, AV, Gomar, GG, Hoffmann, LV, Rutckeviski, R, de Andrade, DP, Smiderle, FR
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3104-3113
Abstract
BACKGROUND & AIMS Fungal β-glucans have been considered as biological response modifiers (BRMs) promoting stimulation of immune system according to numerous scientific publications performed in vitro and in vivo. Some clinical trials involving such compounds started to be published since 1980's. This systematic review aimed to compile and compare clinical studies using these β-glucans as adjuvants on patients undergoing cancer treatment. Healthy subjects and β-glucans from other sources were excluded. METHODS It was developed according to PRISMA-P guidelines (PROSPERO registered n. CRD42020151539), using PICO criteria and the following databases: PubMed, Scielo and LILACS. RESULTS We found 1018 articles and after removing duplicated records, select by title/abstract and full-text, only 9 studies remained and 7 more were manually added, totalizing 16 trials involving 1650 patients, with arm sizes varying from 9 until 200 patients. The selected studies (published since 1992-2018) included subjects with diagnosis of 9 types of cancer. The studies used different sources of β-glucans, such as yeast (Saccharomyces cerevisiae), mushrooms (Lentinula edodes and Schizophyllum commune) and non-described fungal sources. CONCLUSIONS It was observed that the administration of β-glucan is safe and well-tolerated. Most of the trials pointed that concomitant administration of β-glucan with chemo or radiotherapy reduced the immune depression caused by such treatments and/or accelerated the recovery of white blood cells counts. However, some articles also commented that no statistical difference was encountered between β-glucan treated vs. control groups, which gives a controversial conclusion about the β-glucan effects. The great diversity among the methodology studies and insufficient information was an impeditive for achieving profound statistical analysis, therefore a narrative report of the included studies was performed indicating that further evidences are required to determine the efficacy of this adjuvant in the cancer treatment.
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6.
Effects of fungal beta-glucans on health - a systematic review of randomized controlled trials.
Vlassopoulou, M, Yannakoulia, M, Pletsa, V, Zervakis, GI, Kyriacou, A
Food & function. 2021;(8):3366-3380
Abstract
INTRODUCTION Beta-glucans are polysaccharides that exhibit a wide range of biological properties as a result of their varying chemical composition. Like all dietary fibers, they avoid catabolism in the upper gastrointestinal tract, and they reach the large intestine undigested. There, they undergo fermentation by the gut microbiota, a process that has potential beneficial effects for the host. The aim of this systematic review is to assess the effects of consumption of beta-(1 → 3,1 → 6)-d-glucans, naturally found in the cell walls of fungi, on health outcomes. METHODS A comprehensive literature search was performed on PubMed, Cochrane Library and Web of Science to retrieve studies that applied randomized controlled trials (RCTs) to investigate the impact of exclusive oral administration of fungal beta-glucans in any form and at any dosage to healthy subjects or patients. RESULTS Thirty-four RCTs, of the 917 records retrieved in total, met the eligibility criteria and are included in the present review. The sources of fungal beta-glucans were Saccharomyces cerevisiae, Aureobasidium pullulans, Pleurotus ostreatus, Lentinula edodes and Ganoderma lucidum, and the dosage of supplementation ranged from 2.5 to 1000 mg daily for up to 6.5 months. The primary physiological outcome of the majority of the interventions was immunomodulation, which resulted in (a) strengthened immune defense that reduces the incidence and symptoms of cold, flu and other respiratory infections and (b) improvement of allergic symptoms. However, the findings on the induction of immune response alterations were inconsistent at the cellular and molecular levels. Another aspect is psychological wellbeing, as the cohorts that received the polysaccharides of interest reported improvement in their mood states as well as amelioration of overall wellbeing. At the same time, it might also be useful as a complementary agent to patients undergoing cancer therapies. Furthermore, supplements containing beta-(1 → 3,1 → 6)-d-glucan administered to overweight/obese adults might have the potential to decrease comorbid conditions associated with obesity. Notably, no adverse event causally related to glucans was recorded. CONCLUSIONS Supplementation with beta-(1 → 3,1 → 6)-d-glucans is well-tolerated, and health-promoting properties are manifested primarily through the potentiation of the immune system. More studies are required to confirm their additional beneficial effects, to establish the optimal dose, and to reveal the underlying molecular mechanisms.
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7.
Biosynthesis of pneumocandin lipopeptides and perspectives for its production and related echinocandins.
Li, Y, Lan, N, Xu, L, Yue, Q
Applied microbiology and biotechnology. 2018;(23):9881-9891
Abstract
Fungal diseases are a global public health problem. Invasive fungal infections pose a serious threat to patients with compromised immune systems, such as those undergoing organ or bone marrow transplants, cancer, or HIV/AIDS. Pneumocandins are antifungal lipohexapeptides of the echinocandin family that noncompetitively inhibit of 1,3-β-glucan synthase of fungal cell wall and provide the precursor for the semisynthesis of caspofungin, which is widely used as first-line therapy for invasive fungal infections. Recently, the biosynthetic steps leading to formation of pneumocandin B0 and echinocandin B have been elucidated, and thus, provide a framework and attractive model for further design new antifungal therapeutics around natural variations in echinocandin structural diversities via genetic and chemical tools. In this article, we analyze the biosynthetic pathway of pneumocandins and other echinocandins, provide an update on the array of pneumocandin analogues generated by genetic manipulation, and summarize advances in the enhancement of pneumocandin B0 production by random mutagenesis and fermentation optimization. We also give offer advice on the development of improved pneumocandin drug candidates and more efficient production of pneumocandin B0.
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8.
What are the advantages of living in a community? A microbial biofilm perspective!
Santos, ALSD, Galdino, ACM, Mello, TP, Ramos, LS, Branquinha, MH, Bolognese, AM, Columbano Neto, J, Roudbary, M
Memorias do Instituto Oswaldo Cruz. 2018;(9):e180212
Abstract
Biofilm formation is the preferred mode of growth lifestyle for many microorganisms, including bacterial and fungal human pathogens. Biofilm is a strong and dynamic structure that confers a broad range of advantages to its members, such as adhesion/cohesion capabilities, mechanical properties, nutritional sources, metabolite exchange platform, cellular communication, protection and resistance to drugs (e.g., antimicrobials, antiseptics, and disinfectants), environmental stresses (e.g., dehydration and ultraviolet light), host immune attacks (e.g., antibodies, complement system, antimicrobial peptides, and phagocytes), and shear forces. Microbial biofilms cause problems in the hospital environment, generating high healthcare costs and prolonged patient stay, which can result in further secondary microbial infections and various health complications. Consequently, both public and private investments must be made to ensure better patient management, as well as to find novel therapeutic strategies to circumvent the resistance and resilience profiles arising from biofilm-associated microbial infections. In this work, we present a general overview of microbial biofilm formation and its relevance within the biomedical context.
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9.
Cyclophilins: Less Studied Proteins with Critical Roles in Pathogenesis.
Singh, K, Winter, M, Zouhar, M, Ryšánek, P
Phytopathology. 2018;(1):6-14
Abstract
Cyclophilins (EC 5.2.1.8) belong to a subgroup of proteins known as immunophilins, which also include FK506-binding proteins and parvulins. Members of the immunophilins have two main characteristic properties: (i) peptidyl-prolyl cis-trans isomerase activity and (ii) the ability to bind immunosuppressant molecules of fungal origin. Cyclophilins are some of the most conserved proteins present in eukaryotes and prokaryotes, and they have been implicated in diverse cellular processes and responses to multiple biotic and abiotic stresses. Cyclophilins have been exploited in humans and plants extensively, but they have only recently received attention in regard to phytopathogens. In Phellinus sulphurascens and species of the genus Leptosphaeria and Phytophthora, high expression of cyclophilins was found to be related to infection. Moreover, recent studies of cyclophilins in certain phytopathogens, such as Magnaporthe oryzae, Botrytis cinerea, Cryphonectria parasitica, and Puccinia triticina, demonstrated their roles as a pathogenicity factors. In addition to pathogenicity, cyclophilins have high affinity for the immunosuppressive drug cyclosporin A, which is a potent antifungal agent. Although cyclophilins are highly conserved in phytopathogens, because they have been less studied, their role remains largely unknown. In this review, we provide detailed information on the cyclophilins in several phytopathogens, including fungi and oomycetes, as well as their role in suppressing plant immunity.
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10.
Ancestral alliances: Plant mutualistic symbioses with fungi and bacteria.
Martin, FM, Uroz, S, Barker, DG
Science (New York, N.Y.). 2017;(6340)
Abstract
Within the plant microbiota, mutualistic fungal and bacterial symbionts are striking examples of microorganisms playing crucial roles in nutrient acquisition. They have coevolved with their hosts since initial plant adaptation to land. Despite the evolutionary distances that separate mycorrhizal and nitrogen-fixing symbioses, these associations share a number of highly conserved features, including specific plant symbiotic signaling pathways, root colonization strategies that circumvent plant immune responses, functional host-microbe interface formation, and the central role of phytohormones in symbiosis-associated root developmental pathways. We highlight recent and emerging areas of investigation relating to these evolutionarily conserved mechanisms, with an emphasis on the more ancestral mycorrhizal associations, and consider to what extent this knowledge can contribute to an understanding of plant-microbiota associations as a whole.