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1.
Apoplastic Proteases: Powerful Weapons against Pathogen Infection in Plants.
Wang, Y, Wang, Y, Wang, Y
Plant communications. 2020;(4):100085
Abstract
Plants associate with diverse microbes that exert beneficial, neutral, or pathogenic effects inside the host. During the initial stages of invasion, the plant apoplast constitutes a hospitable environment for invading microbes, providing both water and nutrients. In response to microbial infection, a number of secreted proteins from host cells accumulate in the apoplastic space, which is related to microbial association or colonization processes. However, the molecular mechanisms underlying plant modulation of the apoplast environment and how plant-secreted proteases are involved in pathogen resistance are still poorly understood. Recently, several studies have reported the roles of apoplastic proteases in plant resistance against bacteria, fungi, and oomycetes. On the other hand, microbe-secreted proteins directly and/or indirectly inhibit host-derived apoplastic proteases to promote infection. These findings illustrate the importance of apoplastic proteases in plant-microbe interactions. Therefore, understanding the protease-mediated apoplastic battle between hosts and pathogens is of fundamental importance for understanding plant-pathogen interactions. Here, we provide an overview of plant-microbe interactions in the apoplastic space. We define the apoplast, summarize the physical and chemical properties of these structures, and discuss the roles of plant apoplastic proteases and pathogen protease inhibitors in host-microbe interactions. Challenges and future perspectives for research into protease-mediated apoplastic interactions are discussed, which may facilitate the engineering of resistant crops.
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2.
PE_PGRS proteins of Mycobacterium tuberculosis: A specialized molecular task force at the forefront of host-pathogen interaction.
De Maio, F, Berisio, R, Manganelli, R, Delogu, G
Virulence. 2020;(1):898-915
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Abstract
To the PE_PGRS protein subfamily belongs a group of surface-exposed mycobacterial antigens that in Mycobacterium tuberculosis (Mtb) H37Rv accounts to more than 65 genes, 51 of which are thought to express a functional protein. PE_PGRS proteins share a conserved structural architecture with three main domains: the N-terminal PE domain; the PGRS domain, that can vary in sequence and size and is characterized by the presence of multiple GGA-GGX amino acid repeats; the highly conserved sequence containing the GRPLI motif that links the PE and PGRS domains; the unique C-terminus end that can vary in size from few to up to ≈ 300 amino acids. pe_pgrs genes emerged in slow-growing mycobacteria and expanded and diversified in MTBC and few other pathogenic mycobacteria. Interestingly, despite sequence homology and apparent redundancy, PE_PGRS proteins seem to have evolved a peculiar function. In this review, we summarize the actual knowledge on this elusive protein family in terms of evolution, structure, and function, focusing on the role of PE_PGRS in TB pathogenesis. We provide an original hypothesis on the role of the PE domain and propose a structural model for the polymorphic PGRS domain that might explain how so similar proteins can have different physiological functions.
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3.
Molecular breeding approaches for production of disease-resilient commercially important tobacco.
Kakar, KU, Nawaz, Z, Cui, Z, Ahemd, N, Ren, X
Briefings in functional genomics. 2020;(1):10-25
Abstract
Tobacco is one of the most widely cultivated nonfood cash crops, a source of income, model organism for plant molecular research, a natural pesticide and of pharmaceutical importance. First domesticated in South Americas, the modern-day tobacco (Nicotiana tabacum) is now cultivated in more than 125 countries to generate revenues worth billions of dollars each year. However, the production of this crop is highly threatened by the global presence of devastating infectious agents, which cause huge fiscal loss. These threats have been battled through breeding for acquiring disease resilience in tobacco plants, first, via conventional and now with the use of modern molecular breeding approaches. For efficacy and precision, the characterization of the genetic components underlying disease resistance is the key tool in tobacco for resistance breeding programs. The past few decades have witnessed significant progress in resilience breeding through advanced molecular techniques. The current review discusses history of tobacco breeding since its time of origin till date, highlighting the most widely used techniques and recent advances in molecular research and strategies for resistance breeding. In addition, we narrate the budding possibilities for the future. This review will provide a comprehensive and valuable information for the tobacco growers and researchers to deal with the destructive infectious diseases.
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4.
Immune-Microbiota Interplay and Colonization Resistance in Infection.
Leshem, A, Liwinski, T, Elinav, E
Molecular cell. 2020;(4):597-613
Abstract
Commensal microbial communities inhabit biological niches in the mammalian host, where they impact the host's physiology through induction of "colonization resistance" against infections by a multitude of molecular mechanisms. These colonization-regulating activities involve microbe-microbe and microbe-host interactions, which induce, through utilization of complex bacterial networks, competition over nutrients, inhibition by antimicrobial peptides, stimulation of the host immune system, and promotion of mucus and intestinal epithelial barrier integrity. Distinct virulent pathogens overcome this colonization resistance and host immunity as part of a hostile takeover of the host niche, leading to clinically overt infection. The following review provides a mechanistic overview of the role of commensal microbes in modulating colonization resistance and pathogenic infections and means by which infectious agents may overcome such inhibition. Last, we outline evidence, unknowns, and challenges in developing strategies to harness this knowledge to treat infections by microbiota transfer, phage therapy, or supplementation by rationally defined bacterial consortia.
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5.
Potential Use of Biotherapeutic Bacteria to Target Colorectal Cancer-Associated Taxa.
Lawrence, GW, Begley, M, Cotter, PD, Guinane, CM
International journal of molecular sciences. 2020;(3)
Abstract
The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. Furthermore, certain microbial signatures and specific taxa have also been associated with the development of diseases, such as obesity; inflammatory bowel disease; and, indeed, colorectal cancer (CRC), which is the focus of this review. By extension, such taxa represent potential therapeutic targets. In particular, the emerging human pathogen Fusobacterium nucleatum represents an important agent in CRC development and its control within the gastrointestinal tract is desirable. This paper reviews the principal bacterial pathogens that have been associated with CRC to date and discusses the in vitro and human studies that have shown the potential use of biotherapeutic strains as a means of targeting CRC-associated bacteria.
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6.
Rapid evolution in plant-microbe interactions - a molecular genomics perspective.
Frantzeskakis, L, Di Pietro, A, Rep, M, Schirawski, J, Wu, CH, Panstruga, R
The New phytologist. 2020;(3):1134-1142
Abstract
Rapid (co-)evolution at multiple timescales is a hallmark of plant-microbe interactions. The mechanistic basis for the rapid evolution largely rests on the features of the genomes of the interacting partners involved. Here, we review recent insights into genomic characteristics and mechanisms that enable rapid evolution of both plants and phytopathogens. These comprise fresh insights in allelic series of matching pairs of resistance and avirulence genes, the generation of novel pathogen effectors, the recently recognised small RNA warfare, and genomic aspects of secondary metabolite biosynthesis. In addition, we discuss the putative contributions of permissive host environments, transcriptional plasticity and the role of ploidy on the interactions. We conclude that the means underlying the rapid evolution of plant-microbe interactions are multifaceted and depend on the particular nature of each interaction.
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7.
Genomics-Assisted Breeding for Quantitative Disease Resistances in Small-Grain Cereals and Maize.
Miedaner, T, Boeven, ALG, Gaikpa, DS, Kistner, MB, Grote, CP
International journal of molecular sciences. 2020;(24)
Abstract
Generating genomics-driven knowledge opens a way to accelerate the resistance breeding process by family or population mapping and genomic selection. Important prerequisites are large populations that are genomically analyzed by medium- to high-density marker arrays and extensive phenotyping across locations and years of the same populations. The latter is important to train a genomic model that is used to predict genomic estimated breeding values of phenotypically untested genotypes. After reviewing the specific features of quantitative resistances and the basic genomic techniques, the possibilities for genomics-assisted breeding are evaluated for six pathosystems with hemi-biotrophic fungi: Small-grain cereals/Fusarium head blight (FHB), wheat/Septoria tritici blotch (STB) and Septoria nodorum blotch (SNB), maize/Gibberella ear rot (GER) and Fusarium ear rot (FER), maize/Northern corn leaf blight (NCLB). Typically, all quantitative disease resistances are caused by hundreds of QTL scattered across the whole genome, but often available in hotspots as exemplified for NCLB resistance in maize. Because all crops are suffering from many diseases, multi-disease resistance (MDR) is an attractive aim that can be selected by specific MDR QTL. Finally, the integration of genomic data in the breeding process for introgression of genetic resources and for the improvement within elite materials is discussed.
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8.
Structural variations and expression profiles of the SARS-CoV-2 host invasion genes in lung cancer.
Ilikci Sagkan, R, Akin-Bali, DF
Journal of medical virology. 2020;(11):2637-2647
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Abstract
Recent days have seen growing evidence of cancer's susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of the effect of genomic differences on the virus' entrance genes in lung cancer. Genetic confirmation of the hypotheses regarding gene expression and mutation pattern of target genes, including angiotensin-converting enzyme-2 (ACE2), transmembrane serine protease 2 (TMPRSS2), basigin (CD147/BSG) and paired basic amino acid cleaving enzyme (FURIN/PCSK3), as well as correlation analysis, was done in relation to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) using in silico analysis. Not only were gene expression and mutation patterns detected, but also there were correlation and survival analysis between ACE2 and other target genes expression levels. The total genetic anomaly carrying rate of target genes, including ACE2, TMPRSS2, CD147/BSG, and FURIN/PCSK3, was determined as 8.1% and 21 mutations were detected, with 7 of these mutations having pathogenic features. p.H34N on the RBD binding residues for SARS-CoV-2 was determined in our LUAD patient group. According to gene expression analysis results, though the TMPRSS2 level was statistically significantly decreased in the LUSC patient group compared to healthy control, the ACE2 level was determined to be high in LUAD and LUSC groups. There were no meaningful differences in the expression of CD147 and FURIN genes. The challenge for today is building the assessment of genomic susceptibility to COVID-19 in lung cancer, requiring detailed experimental laboratory studies, in addition to in silico analyses, as a way of assessing the mechanism of novel virus invasion that can be used in the development of effective SARS-CoV-2 therapy.
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9.
CRISPR/Cas9 for development of disease resistance in plants: recent progress, limitations and future prospects.
Ahmad, S, Wei, X, Sheng, Z, Hu, P, Tang, S
Briefings in functional genomics. 2020;(1):26-39
Abstract
Several plant pathogens severely affect crop yield and quality, thereby threatening global food security. In order to cope with this challenge, genetic improvement of plant disease resistance is required for sustainable agricultural production, for which conventional breeding is unlikely to do enough. Luckily, genome editing systems that particularly clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) has revolutionized crop improvement by enabling robust and precise targeted genome modifications. It paves the way towards new methods for genetic improvement of plant disease resistance and accelerates resistance breeding. In this review, the challenges, limitations and prospects for conventional breeding and the applications of CRISPR/Cas9 system for the development of transgene-free disease-resistant crops are discussed.
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10.
The impact of PARPs and ADP-ribosylation on inflammation and host-pathogen interactions.
Fehr, AR, Singh, SA, Kerr, CM, Mukai, S, Higashi, H, Aikawa, M
Genes & development. 2020;(5-6):341-359
Abstract
Poly-adenosine diphosphate-ribose polymerases (PARPs) promote ADP-ribosylation, a highly conserved, fundamental posttranslational modification (PTM). PARP catalytic domains transfer the ADP-ribose moiety from NAD+ to amino acid residues of target proteins, leading to mono- or poly-ADP-ribosylation (MARylation or PARylation). This PTM regulates various key biological and pathological processes. In this review, we focus on the roles of the PARP family members in inflammation and host-pathogen interactions. Here we give an overview the current understanding of the mechanisms by which PARPs promote or suppress proinflammatory activation of macrophages, and various roles PARPs play in virus infections. We also demonstrate how innovative technologies, such as proteomics and systems biology, help to advance this research field and describe unanswered questions.