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1.
Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms.
Vanzolini, T, Bruschi, M, Rinaldi, AC, Magnani, M, Fraternale, A
International journal of molecular sciences. 2022;(1)
Abstract
Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. This review aims to focus on synthetic peptides and elucidate their multifaceted mechanisms of action as antiviral, antibacterial and antifungal agents. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections.
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2.
Carotenoids and Their Biosynthesis in Fungi.
Sandmann, G
Molecules (Basel, Switzerland). 2022;(4)
Abstract
Carotenoids represent a class of pigmented terpenoids. They are distributed in all taxonomic groups of fungi. Most of the fungal carotenoids differ in their chemical structures to those from other organisms. The general function of carotenoids in heterotrophic organisms is protection as antioxidants against reactive oxygen species generated by photosensitized reactions. Furthermore, carotenoids are metabolized to apocarotenoids by oxidative cleavage. This review presents the current knowledge on fungal-specific carotenoids, their occurrence in different taxonomic groups, and their biosynthesis and conversion into trisporic acids. The outline of the different pathways was focused on the reactions and genes involved in not only the known pathways, but also suggested the possible mechanisms of reactions, which may occur in several non-characterized pathways in different fungi. Finally, efforts and strategies for genetic engineering to enhance or establish pathways for the production of various carotenoids in carotenogenic or non-carotenogenic yeasts were highlighted, addressing the most-advanced producers of each engineered yeast, which offered the highest biotechnological potentials as production systems.
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3.
Surviving the odds: From perception to survival of fungal phytopathogens under host-generated oxidative burst.
Singh, Y, Nair, AM, Verma, PK
Plant communications. 2021;(3):100142
Abstract
Fungal phytopathogens pose a serious threat to global crop production. Only a handful of strategies are available to combat these fungal infections, and the increasing incidence of fungicide resistance is making the situation worse. Hence, the molecular understanding of plant-fungus interactions remains a primary focus of plant pathology. One of the hallmarks of host-pathogen interactions is the overproduction of reactive oxygen species (ROS) as a plant defense mechanism, collectively termed the oxidative burst. In general, high accumulation of ROS restricts the growth of pathogenic organisms by causing localized cell death around the site of infection. To survive the oxidative burst and achieve successful host colonization, fungal phytopathogens employ intricate mechanisms for ROS perception, ROS neutralization, and protection from ROS-mediated damage. Together, these countermeasures maintain the physiological redox homeostasis that is essential for cell viability. In addition to intracellular antioxidant systems, phytopathogenic fungi also deploy interesting effector-mediated mechanisms for extracellular ROS modulation. This aspect of plant-pathogen interactions is significantly under-studied and provides enormous scope for future research. These adaptive responses, broadly categorized into "escape" and "exploitation" mechanisms, are poorly understood. In this review, we discuss the oxidative stress response of filamentous fungi, their perception signaling, and recent insights that provide a comprehensive understanding of the distinct survival mechanisms of fungal pathogens in response to the host-generated oxidative burst.
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4.
Snow mold of winter cereals: a complex disease and a challenge for resistance breeding.
Ponomareva, ML, Gorshkov, VY, Ponomarev, SN, Korzun, V, Miedaner, T
TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik. 2021;(2):419-433
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Abstract
Snow mold resistance is a complex quantitative trait highly affected by environmental conditions during winter that must be addressed by resistance breeding. Snow mold resistance in winter cereals is an important trait for many countries in the Northern Hemisphere. The disease is caused by at least four complexes of soilborne fungi and oomycetes of which Microdochium nivale and M. majus are among the most common pathogens. They have a broad host range covering all winter and spring cereals and can basically affect all plant growth stages and organs. Their attack leads to a low germination rate, and/or pre- and post-emergence death of seedlings after winter and, depending on largely unknown environmental conditions, also to foot rot, leaf blight, and head blight. Resistance in winter wheat and triticale is governed by a multitude of quantitative trait loci (QTL) with mainly additive effects highly affected by genotype × environment interaction. Snow mold resistance interacts with winter hardiness in a complex way leading to a co-localization of resistance QTLs with QTLs/genes for freezing tolerance. In practical breeding, a multistep procedure is necessary with (1) freezing tolerance tests, (2) climate chamber tests for snow mold resistance, and (3) field tests in locations with and without regularly occurring snow cover. In the future, resistance sources should be genetically characterized also in rye by QTL mapping or genome-wide association studies. The development of genomic selection procedures should be prioritized in breeding research.
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5.
Glucose - The X factor for the survival of human fungal pathogens and disease progression in the host.
Qadri, H, Qureshi, MF, Mir, MA, Shah, AH
Microbiological research. 2021;:126725
Abstract
The incidence of human fungal infections is increasing due to the expansion of the immunocompromised patient population. The continuous use of different antifungal agents has eventually resulted in the establishment of resistant fungal species. The fungal pathogens unfold multiple resistance strategies to successfully tackle the effect of different antifungal agents. For the successful colonization and establishment of infection inside the host, the pathogenic fungi switch to the process of metabolic flexibility to regulate distinct nutrient uptake systems as well as to modulate their metabolism accordingly. Glucose the most favourable carbon source helps carry out the important survival and niche colonization processes. Adopting glucose as the center, this review has been put forward to provide an outline of the important processes like growth, the progression of infection, and the metabolism regulated by glucose, affecting the pathogenicity and virulence traits in the human pathogenic fungi. This could help in the identification of better treatment options and appropriate target-oriented antifungal drugs based on the glucose-regulated pathways and processes. In the article, we have also presented a summary of the novel studies and findings pointing to glucose-based potential therapeutic avenues to be explored to tackle the problem of globally increasing multidrug-resistant human fungal infections.
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6.
Heat stress in macrofungi: effects and response mechanisms.
Luo, L, Zhang, S, Wu, J, Sun, X, Ma, A
Applied microbiology and biotechnology. 2021;(20):7567-7576
Abstract
Temperature is one of the key factors that affects the growth and development of macrofungi. Heat stress not only negatively affects the morphology and growth rate of macrofungi, but also destroys cell structures and influences cell metabolism. Due to loosed structure of cell walls and increased membrane fluidity, which caused by heat stress, the outflow of intracellular nutrients makes macrofungi more vulnerable to invasion by pathogens. Macrofungi accumulate reactive oxygen species (ROS), Ca2+, and nitric oxide (NO) when heat-stressed, which transmit and amplify the heat stimulation signal through intracellular signal transduction pathways. Through regulation of some transcription factors including heat response factors (HSFs), POZCP26 and MYB, macrofungi respond to heat stress by different mechanisms. In this paper, we present mechanisms used by macrofungi to adapt and survive under heat stress conditions, including antioxidant defense systems that eliminate the excess ROS, increase in trehalose levels that prevent enzymes and proteins deformation, and stabilize cell structures and heat shock proteins (HSPs) that repair damaged proteins and synthesis of auxins, which increase the activity of antioxidant enzymes. All of these help macrofungi resist and adapt to heat stress. KEY POINTS • The effects of heat stress on macrofungal growth and development were described. • The respond mechanisms to heat stress in macrofungi were summarized. • The further research directions of heat stress in macrofungi were discussed.
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7.
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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8.
Microorganisms: A Potential Source of Bioactive Molecules for Antioxidant Applications.
Rani, A, Saini, KC, Bast, F, Mehariya, S, Bhatia, SK, Lavecchia, R, Zuorro, A
Molecules (Basel, Switzerland). 2021;(4)
Abstract
Oxidative stress originates from an elevated intracellular level of free oxygen radicals that cause lipid peroxidation, protein denaturation, DNA hydroxylation, and apoptosis, ultimately impairing cell viability. Antioxidants scavenge free radicals and reduce oxidative stress, which further helps to prevent cellular damage. Medicinal plants, fruits, and spices are the primary sources of antioxidants from time immemorial. In contrast to plants, microorganisms can be used as a source of antioxidants with the advantage of fast growth under controlled conditions. Further, microbe-based antioxidants are nontoxic, noncarcinogenic, and biodegradable as compared to synthetic antioxidants. The present review aims to summarize the current state of the research on the antioxidant activity of microorganisms including actinomycetes, bacteria, fungi, protozoa, microalgae, and yeast, which produce a variety of antioxidant compounds, i.e., carotenoids, polyphenols, vitamins, and sterol, etc. Special emphasis is given to the mechanisms and signaling pathways followed by antioxidants to scavenge Reactive Oxygen Species (ROS), especially for those antioxidant compounds that have been scarcely investigated so far.
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9.
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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10.
Phosphonates enantiomers receiving with fungal enzymatic systems.
Serafin-Lewańczuk, M, Brzezińska-Rodak, M, Lubiak-Kozłowska, K, Majewska, P, Klimek-Ochab, M, Olszewski, TK, Żymańczyk-Duda, E
Microbial cell factories. 2021;(1):81
Abstract
BACKGROUND Phosphonates derivatives are in the area of interests because of their unique chemical-physical features. These compounds manifest variety of biological interactions within the sensitive living cells, including impact on particular enzymes activities. Biological "cause and effect" interactions are based upon the specific matching between the structures and/or compounds and this is usually the result of proper optical configurations of particular chiral moieties. Presented research is targeted to the phosphonates with the heteroatom incorporated in their side functionalities. Such molecules are described as possible substrates of bioconversion for the first time lately and this field is not fully explored. RESULTS Presented research is targeted to the synthesis of pure hetero-phosphonates enantiomers. The catalytic activity of yeasts and moulds were tested towards two substrates: the thienyl and imidazole phosphonates to resolve their racemic mixtures. Biotransformations conditions differed depending on the outcome, what included changing of following parameters: type of cultivation media, bioprocess duration (24-72 h), additional biocatalyst pre-treatment (24-48 h starvation step triggering the secondary metabolism). (S)-1-amino-1-(3-thienyl)methylphosphonate was produced with the assistance of R. mucilaginosa or A. niger (e.e. up to 98% and yield up to 100%), starting from the 3 mM of substrate racemic mixture. Bioconversion of racemic mixture of 3 mM of (1-amino-1-(4-imidazole)methylphosphonic acid) resulted in the synthesis of S-isomer (up to 95% of e.e.; 100% of yield) with assistance of R. mucilaginosa. 24 h biotransformation was conducted with biomass preincubated under 48-hour starvation conditions. Such stereoselective resolution of the racemic mixtures of substrates undergoes under kinetic control with the conversion of one from the enantiomers. CONCLUSIONS Composition of the culturing media and pre-incubation in conditions of nutrient deficiency were significant factors influencing the results of kinetic resolution of racemic mixtures of phosphonic substrates and influencing the economic side of the biocatalysis e.g. by determining the duration of whole biocatalytic process.