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Showing papers in "Frontiers in Microbiology in 2021"


Journal ArticleDOI
TL;DR: In this article, the authors discuss the mechanisms by which RNA viruses beyond just SARS-CoV-2 have been connected to long-term health consequences, and review literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Abstract: The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.

336 citations


Journal ArticleDOI
TL;DR: The emergence and spread of infectious diseases with pandemic potential occurred regularly throughout history as discussed by the authors, and many infectious diseases leading to pandemics are caused by zoonotic pathogens that were transmitted to humans due to increased contacts with animals through breeding, hunting and global trade activities.
Abstract: The emergence and spread of infectious diseases with pandemic potential occurred regularly throughout history. Major pandemics and epidemics such as plague, cholera, flu, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have already afflicted humanity. The world is now facing the new coronavirus disease 2019 (COVID-19) pandemic. Many infectious diseases leading to pandemics are caused by zoonotic pathogens that were transmitted to humans due to increased contacts with animals through breeding, hunting and global trade activities. The understanding of the mechanisms of transmission of pathogens to humans allowed the establishment of methods to prevent and control infections. During centuries, implementation of public health measures such as isolation, quarantine and border control helped to contain the spread of infectious diseases and maintain the structure of the society. In the absence of pharmaceutical interventions, these containment methods have still been used nowadays to control COVID-19 pandemic. Global surveillance programs of water-borne pathogens, vector-borne diseases and zoonotic spillovers at the animal-human interface are of prime importance to rapidly detect the emergence of infectious threats. Novel technologies for rapid diagnostic testing, contact tracing, drug repurposing, biomarkers of disease severity as well as new platforms for the development and production of vaccines are needed for an effective response in case of pandemics.

224 citations


Journal ArticleDOI
TL;DR: In this paper, the potential of AMPs as alternatives to antibiotics, challenges toward clinical implementation and strategies to improve the success rate of AMP in clinical trials, emphasizing the lessons we could learn from these trials.
Abstract: Antimicrobial peptides (AMPs) or host defense peptides protect the host against various pathogens such as yeast, fungi, viruses and bacteria. AMPs also display immunomodulatory properties ranging from the modulation of inflammatory responses to the promotion of wound healing. More interestingly, AMPs cause cell disruption through non-specific interactions with the membrane surface of pathogens. This is most likely responsible for the low or limited emergence of bacterial resistance against many AMPs. Despite the increasing number of antibiotic-resistant bacteria and the potency of novel AMPs to combat such pathogens, only a few AMPs are in clinical use. Therefore, the current review describes (i) the potential of AMPs as alternatives to antibiotics, (ii) the challenges toward clinical implementation of AMPs and (iii) strategies to improve the success rate of AMPs in clinical trials, emphasizing the lessons we could learn from these trials.

128 citations


Journal ArticleDOI
TL;DR: In this paper, a review of the state-of-the-art ML methods and respective software applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities, is presented.
Abstract: The number of microbiome-related studies has notably increased the availability of data on human microbiome composition and function. These studies provide the essential material to deeply explore host-microbiome associations and their relation to the development and progression of various complex diseases. Improved data-analytical tools are needed to exploit all information from these biological datasets, taking into account the peculiarities of microbiome data, i.e., compositional, heterogeneous and sparse nature of these datasets. The possibility of predicting host-phenotypes based on taxonomy-informed feature selection to establish an association between microbiome and predict disease states is beneficial for personalized medicine. In this regard, machine learning (ML) provides new insights into the development of models that can be used to predict outputs, such as classification and prediction in microbiology, infer host phenotypes to predict diseases and use microbial communities to stratify patients by their characterization of state-specific microbial signatures. Here we review the state-of-the-art ML methods and respective software applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on the application of ML in microbiome studies related to association and clinical use for diagnostics, prognostics, and therapeutics. Although the data presented here is more related to the bacterial community, many algorithms could be applied in general, regardless of the feature type. This literature and software review covering this broad topic is aligned with the scoping review methodology. The manual identification of data sources has been complemented with: (1) automated publication search through digital libraries of the three major publishers using natural language processing (NLP) Toolkit, and (2) an automated identification of relevant software repositories on GitHub and ranking of the related research papers relying on learning to rank approach.

105 citations


Journal ArticleDOI
TL;DR: In this paper, the importance of Azotobacter species was highlighted as both important free-living N2fixing bacteria and potential bacterial biofertilizer with proven efficacy for plant nutrition and biological soil fertility.
Abstract: Biological nitrogen fixation (BNF) refers to a microbial mediated process based upon an enzymatic "Nitrogenase" conversion of atmospheric nitrogen (N2) into ammonium readily absorbable by roots. N2-fixing microorganisms collectively termed as "diazotrophs" are able to fix biologically N2 in association with plant roots. Specifically, the symbiotic rhizobacteria induce structural and physiological modifications of bacterial cells and plant roots into specialized structures called nodules. Other N2-fixing bacteria are free-living fixers that are highly diverse and globally widespread in cropland. They represent key natural source of nitrogen (N) in natural and agricultural ecosystems lacking symbiotic N fixation (SNF). In this review, the importance of Azotobacter species was highlighted as both important free-living N2-fixing bacteria and potential bacterial biofertilizer with proven efficacy for plant nutrition and biological soil fertility. In addition, we described Azotobacter beneficial plant promoting traits (e.g., nutrient use efficiency, protection against phytopathogens, phytohormone biosynthesis, etc.). We shed light also on the agronomic features of Azotobacter that are likely an effective component of integrated plant nutrition strategy, which contributes positively to sustainable agricultural production. We pointed out Azotobacter based-biofertilizers, which possess unique characteristics such as cyst formation conferring resistance to environmental stresses. Such beneficial traits can be explored profoundly for the utmost aim to research and develop specific formulations based on inoculant Azotobacter cysts. Furthermore, Azotobacter species still need to be wisely exploited in order to address specific agricultural challenges (e.g., nutrient deficiencies, biotic and abiotic constraints) taking into consideration several variables including their biological functions, synergies and multi-trophic interactions, and biogeography and abundance distribution.

93 citations


Journal ArticleDOI
TL;DR: In this article, an outbreak of SARS-CoV-2 in a mink farm was reported in the Netherlands and since then, COVID-19 has reached numerous mink farms in Denmark, Denmark, United States, France, Greece, Italy, Spain, Sweden, Poland, Lithuania, and Canada.
Abstract: Mink are small carnivores of the Mustelidae family. The American mink is the most common and was imported to Europe, Asia, and Latin America for breeding, as its fur is very popular. Denmark, the Netherlands, and China are the biggest producers of mink. Mink farms with a high population density in very small areas and a low level of genetic heterogeneity are places conducive to contagion. The mink's receptor for SARS-CoV-2 is very similar to that of humans. Experimental models have shown the susceptibility of the ferret, another mustelid, to become infected with SARS-CoV-2 and to transmit it to other ferrets. On April 23, 2020, for the first time, an outbreak of SARS-CoV-2 in a mink farm was reported in the Netherlands. Since then, COVID-19 has reached numerous mink farms in the Netherlands, Denmark, United States, France, Greece, Italy, Spain, Sweden, Poland, Lithuania, and Canada. Not only do mink become infected from each other, but also they are capable of infecting humans, including with virus variants that have mutated in mink. Human infection with variant mink viruses with spike mutations led to the culling in Denmark of all mink in the country. Several animals can be infected with SARS-CoV-2. However, anthropo-zoonotic outbreaks have only been reported in mink farms. The rapid spread of SARS-CoV-2 in mink farms raises questions regarding their potential role at the onset of the pandemic and the impact of mutants on viral fitness, contagiousness, pathogenicity, re-infections with different mutants, immunotherapy, and vaccine efficacy.

89 citations


Journal ArticleDOI
TL;DR: A review of antibiotic resistance mechanisms in bacterial biofilm and novel therapeutic strategies for combating biofilm mediated infections is presented in this article, where the authors focus on these recent therapeutic strategies that may lead to the development of effective biofilm inhibitors than conventional treatments.
Abstract: Biofilm formation is a major concern in various sectors and cause severe problems to public health, medicine, and industry. Bacterial biofilm formation is a major persistent threat, as it increases morbidity and mortality, thereby imposing heavy economic pressure on the healthcare sector. Bacterial biofilms also strengthen biofouling, affecting shipping functions, and the offshore industries in their natural environment. Besides, they accomplish harsh roles in the corrosion of pipelines in industries. At biofilm state, bacterial pathogens are significantly resistant to external attack like antibiotics, chemicals, disinfectants, etc. Within a cell, they are insensitive to drugs and host immune responses. The development of intact biofilms is very critical for the spreading and persistence of bacterial infections in the host. Further, bacteria form biofilms on every probable substratum, and their infections have been found in plants, livestock, and humans. The advent of novel strategies for treating and preventing biofilm formation has gained a great deal of attention. To prevent the development of resistant mutants, a feasible technique that may target adhesive properties without affecting the bacterial vitality is needed. This stimulated research is a rapidly growing field for applicable control measures to prevent biofilm formation. Therefore, this review discusses the current understanding of antibiotic resistance mechanisms in bacterial biofilm and intensely emphasized the novel therapeutic strategies for combating biofilm mediated infections. The forthcoming experimental studies will focus on these recent therapeutic strategies that may lead to the development of effective biofilm inhibitors than conventional treatments.

83 citations


Journal ArticleDOI
TL;DR: In this article, a review on the microbial nano-techniques that were used to produce various metallic and non-metallic nanoparticles and their "signal jamming effects" to inhibit biofilm formation is presented.
Abstract: The emergence of bacterial resistance to antibiotics has led to the search for alternate antimicrobial treatment strategies. Engineered nanoparticles (NPs) for efficient penetration into a living system have become more common in the world of health and hygiene. The use of microbial enzymes/proteins as a potential reducing agent for synthesizing NPs has increased rapidly in comparison to physical and chemical methods. It is a fast, environmentally safe, and cost-effective approach. Among the biogenic sources, fungi and bacteria are preferred not only for their ability to produce a higher titer of reductase enzyme to convert the ionic forms into their nano forms, but also for their convenience in cultivating and regulating the size and morphology of the synthesized NPs, which can effectively reduce the cost for large-scale manufacturing. Effective penetration through exopolysaccharides of a biofilm matrix enables the NPs to inhibit the bacterial growth. Biofilm is the consortia of sessile groups of microbial cells that are able to adhere to biotic and abiotic surfaces with the help extracellular polymeric substances and glycocalyx. These biofilms cause various chronic diseases and lead to biofouling on medical devices and implants. The NPs penetrate the biofilm and affect the quorum-sensing gene cascades and thereby hamper the cell-to-cell communication mechanism, which inhibits biofilm synthesis. This review focuses on the microbial nano-techniques that were used to produce various metallic and non-metallic nanoparticles and their "signal jamming effects" to inhibit biofilm formation. Detailed analysis and discussion is given to their interactions with various types of signal molecules and the genes responsible for the development of biofilm.

81 citations


Journal ArticleDOI
TL;DR: In this paper, a review examines the pathogens, potentially pathogenic microorganisms and ARGs which may be found in animal manure, and evaluates their effect on human health through their exposure to soil and plant resistomes.
Abstract: Antibiotic resistance genes (ARGs) are a relatively new type of pollutant The rise in antibiotic resistance observed recently is closely correlated with the uncontrolled and widespread use of antibiotics in agriculture and the treatment of humans and animals Resistant bacteria have been identified in soil, animal feces, animal housing (eg, pens, barns, or pastures), the areas around farms, manure storage facilities, and the guts of farm animals The selection pressure caused by the irrational use of antibiotics in animal production sectors not only promotes the survival of existing antibiotic-resistant bacteria but also the development of new resistant forms One of the most critical hot-spots related to the development and dissemination of ARGs is livestock and poultry production Manure is widely used as a fertilizer thanks to its rich nutrient and organic matter content However, research indicates that its application may pose a severe threat to human and animal health by facilitating the dissemination of ARGs to arable soil and edible crops This review examines the pathogens, potentially pathogenic microorganisms and ARGs which may be found in animal manure, and evaluates their effect on human health through their exposure to soil and plant resistomes It takes a broader view than previous studies of this topic, discussing recent data on antibiotic use in farm animals and the effect of these practices on the composition of animal manure; it also examines how fertilization with animal manure may alter soil and crop microbiomes, and proposes the drivers of such changes and their consequences for human health

78 citations


Journal ArticleDOI
TL;DR: In this article, the authors synthesize research on the microbiota of aquatic vertebrates and discuss the impact of emerging stressors on aquatic microbial communities using two case studies, that of toxic cyanobacteria and microplastics.
Abstract: Aquatic ecosystems are under increasing stress from global anthropogenic and natural changes, including climate change, eutrophication, ocean acidification, and pollution. In this critical review, we synthesize research on the microbiota of aquatic vertebrates and discuss the impact of emerging stressors on aquatic microbial communities using two case studies, that of toxic cyanobacteria and microplastics. Most studies to date are focused on host-associated microbiomes of individual organisms, however, few studies take an integrative approach to examine aquatic vertebrate microbiomes by considering both host-associated and free-living microbiota within an ecosystem. We highlight what is known about microbiota in aquatic ecosystems, with a focus on the interface between water, fish, and marine mammals. Though microbiomes in water vary with geography, temperature, depth, and other factors, core microbial functions such as primary production, nitrogen cycling, and nutrient metabolism are often conserved across aquatic environments. We outline knowledge on the composition and function of tissue-specific microbiomes in fish and marine mammals and discuss the environmental factors influencing their structure. The microbiota of aquatic mammals and fish are highly unique to species and a delicate balance between respiratory, skin, and gastrointestinal microbiota exists within the host. In aquatic vertebrates, water conditions and ecological niche are driving factors behind microbial composition and function. We also generate a comprehensive catalog of marine mammal and fish microbial genera, revealing commonalities in composition and function among aquatic species, and discuss the potential use of microbiomes as indicators of health and ecological status of aquatic ecosystems. We also discuss the importance of a focus on the functional relevance of microbial communities in relation to organism physiology and their ability to overcome stressors related to global change. Understanding the dynamic relationship between aquatic microbiota and the animals they colonize is critical for monitoring water quality and population health.

75 citations


Journal ArticleDOI
TL;DR: The EcoCyc model-organism database collects and summarizes experimental data for Escherichia coli K-12 as discussed by the authors, including metabolic, transport, DNA repair, and regulation of gene expression.
Abstract: The EcoCyc model-organism database collects and summarizes experimental data for Escherichia coli K-12. EcoCyc is regularly updated by the manual curation of individual database entries, such as genes, proteins, and metabolic pathways, and by the programmatic addition of results from select high-throughput analyses. Updates to the Pathway Tools software that supports EcoCyc and to the web interface that enables user access have continuously improved its usability and expanded its functionality. This article highlights recent improvements to the curated data in the areas of metabolism, transport, DNA repair, and regulation of gene expression. New and revised data analysis and visualization tools include an interactive metabolic network explorer, a circular genome viewer, and various improvements to the speed and usability of existing tools.

Journal ArticleDOI
TL;DR: In this article, a review aimed to illustrate epidemiologically the carbapenem resistance in Pseudomonas aeruginosa, including the resistance rates worldwide and the carbinemase-encoding genes along with the mobile genetic elements responsible for the horizontal dissemination of the drug resistance determinants.
Abstract: Carbapenem-resistant Pseudomonas aeruginosa is one of the major concerns in clinical settings impelling a great challenge to antimicrobial therapy for patients with infections caused by the pathogen. While membrane permeability, together with derepression of the intrinsic beta-lactamase gene, is the global prevailing mechanism of carbapenem resistance in P. aeruginosa, the acquired genes for carbapenemases need special attention because horizontal gene transfer through mobile genetic elements, such as integrons, transposons, plasmids, and integrative and conjugative elements, could accelerate the dissemination of the carbapenem-resistant P. aeruginosa. This review aimed to illustrate epidemiologically the carbapenem resistance in P. aeruginosa, including the resistance rates worldwide and the carbapenemase-encoding genes along with the mobile genetic elements responsible for the horizontal dissemination of the drug resistance determinants. Moreover, the modular mobile elements including the carbapenemase-encoding gene, also known as the P. aeruginosa resistance islands, are scrutinized mostly for their structures.

Journal ArticleDOI
TL;DR: In this article, the authors discuss Mtb phenotypic and genotypic changes driving resistance, including changes in cell envelope components, as well as recently described intrinsic and extrinsic factors promoting resistance emergence and transmission.
Abstract: In the last two decades, multi (MDR), extensively (XDR), extremely (XXDR) and total (TDR) drug-resistant Mycobacterium tuberculosis (Mtb) strains have emerged as a threat to public health worldwide, stressing the need to develop new tuberculosis (TB) prevention and treatment strategies It is estimated that in the next 35 years, drug-resistant TB will kill around 75 million people and cost the global economy $167 trillion Indeed, the COVID-19 pandemic alone may contribute with the development of 63 million new TB cases due to lack of resources and enforced confinement in TB endemic areas Evolution of drug-resistant Mtb depends on numerous factors, such as bacterial fitness, strain's genetic background and its capacity to adapt to the surrounding environment, as well as host-specific and environmental factors Whole-genome transcriptomics and genome-wide association studies in recent years have shed some insights into the complexity of Mtb drug resistance and have provided a better understanding of its underlying molecular mechanisms In this review, we will discuss Mtb phenotypic and genotypic changes driving resistance, including changes in cell envelope components, as well as recently described intrinsic and extrinsic factors promoting resistance emergence and transmission We will further explore how drug-resistant Mtb adapts differently than drug-susceptible strains to the lung environment at the cellular level, modulating Mtb-host interactions and disease outcome, and novel next generation sequencing (NGS) strategies to study drug-resistant TB

Journal ArticleDOI
TL;DR: In this paper, the authors showed that the nanoparticle protein capping agent that can be involved in reduction of silver ions to AgNPs and their stabilization was identified using LC-MS/MS.
Abstract: The increasing number of multi-drug-resistant bacteria and cancer cases, that are a real threat to humankind, forces research world to develop new weapons to deal with it. Biogenic silver nanoparticles (AgNPs) are considered as a solution to this problem. Biosynthesis of AgNPs is regarded as a green, eco-friendly, low-priced process that provides small and biocompatible nanostructures with antimicrobial and anticancer activities and potential application in medicine. The biocompatibility of these nanoparticles is related to the coating with biomolecules of natural origin. The synthesis of AgNPs from actinobacterial strain was confirmed using UV-Vis spectroscopy while their morphology, crystalline structure, stability, and coating were characterized using, transmission electron microscopy (TEM), X-ray diffraction (XRD), Zeta potential and Fourier transform infrared spectroscopy (FTIR). Antibacterial activity of biogenic AgNPs was evaluated by determination of minimum inhibitory and minimum biocidal concentrations (MIC and MBC) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The potential mechanism of antibacterial action of AgNPs was determined by measurement of ATP level. Since the use of AgNPs in biomedical applications depend on their safety, the in vitro cytotoxicity of biosynthesized AgNPs on MCF-7 human breast cancer cell line and murine macrophage cell line RAW 264.7 using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, cell lactate dehydrogenase (LDH) release and measurement of reactive oxygen species (ROS) level were assessed. The nanoparticle protein capping agent that can be involved in reduction of silver ions to AgNPs and their stabilization was identified using LC-MS/MS. Nanoparticles were spherical in shape, small in size (mean 13.2 nm), showed crystalline nature, good stability (-18.7 mV) and presence of capping agents. They exhibited antibacterial activity (MIC of 8-128 μg ml-1, MBC of 64-256 μg ml-1) and significantly decreased ATP levels in bacterial cells after treatment with different concentrations of AgNPs. The in vitro analysis showed that the AgNPs demonstrated dose-dependent cytotoxicity against RAW 264.7 macrophages and MCF-7 breast cancer cells but higher against the latter than the former. Cell viability decrease was found to be 42.2-14.2 and 38.0-15.5% while LDH leakage 14.6-42.7% and 19.0-45.0%, respectively. IC50 values calculated for MTT assay was found to be 16.3 and 12.0 μg ml-1 and for LDH assay 102.3 and 76.2 μg ml-1, respectively. Moreover, MCF-7 cells released a greater amount of ROS than RAW 264.7 macrophages during stimulation with all tested concentrations of AgNPs (1.47-3.13 and 1.02-2.58 fold increase, respectively). The SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) analysis revealed the presence of five protein bands at a molecular weight between 31.7 and 280.9 kDa. These proteins showed the highest homology to hypothetical proteins and porins from E. coli, Delftia sp. and Pseudomonas rhodesiae. Based on obtained results it can be concluded that biogenic AgNPs were capped with proteins and demonstrated potential as antimicrobial and anticancer agent.

Journal ArticleDOI
TL;DR: In this article, the authors highlight the present scenario of increasing antimicrobial-resistance in pathogenic bacteria and the clinical importance of unconventional or non-antibiotic therapies to thwart the infectious pathogenic microorganisms.
Abstract: The looming problem of resistance to antibiotics in microorganisms is a global health concern. The drug-resistant microorganisms originating from anthropogenic sources and commercial livestock farming have posed serious environmental and health challenges. Antibiotic-resistant genes constituting the environmental "resistome" get transferred to human and veterinary pathogens. Hence, deciphering the origin, mechanism and extreme of transfer of these genetic factors into pathogens is extremely important to develop not only the therapeutic interventions to curtail the infections, but also the strategies to avert the menace of microbial drug-resistance. Clinicians, researchers and policymakers should jointly come up to develop the strategies to prevent superfluous exposure of pathogens to antibiotics in non-clinical settings. This article highlights the present scenario of increasing antimicrobial-resistance in pathogenic bacteria and the clinical importance of unconventional or non-antibiotic therapies to thwart the infectious pathogenic microorganisms.

Journal ArticleDOI
TL;DR: The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx as discussed by the authors.
Abstract: The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (p = 0.006), and increased local inflammation (p < 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (p = 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.

Journal ArticleDOI
TL;DR: In this paper, a review on the lichen symbiosis in general and especially on the model species Lobaria pulmonaria L. Hoffm, which is a large foliose lichen that occurs worldwide on tree trunks in undisturbed forests with long ecological continuity.
Abstract: Lichens represent self-supporting symbioses, which occur in a wide range of terrestrial habitats and which contribute significantly to mineral cycling and energy flow at a global scale. Lichens usually grow much slower than higher plants. Nevertheless, lichens can contribute substantially to biomass production. This review focuses on the lichen symbiosis in general and especially on the model species Lobaria pulmonaria L. Hoffm., which is a large foliose lichen that occurs worldwide on tree trunks in undisturbed forests with long ecological continuity. In comparison to many other lichens, L. pulmonaria is less tolerant to desiccation and highly sensitive to air pollution. The name-giving mycobiont (belonging to the Ascomycota), provides a protective layer covering a layer of the green-algal photobiont (Dictyochloropsis reticulata) and interspersed cyanobacterial cell clusters (Nostoc spec.). Recently performed metaproteome analyses confirm the partition of functions in lichen partnerships. The ample functional diversity of the mycobiont contrasts the predominant function of the photobiont in production (and secretion) of energy-rich carbohydrates, and the cyanobiont’s contribution by nitrogen fixation. In addition, high throughput and state-of-the-art metagenomics and community fingerprinting, metatranscriptomics, and MS-based metaproteomics identify the bacterial community present on L. pulmonaria as a surprisingly abundant and structurally integrated element of the lichen symbiosis. Comparative metaproteome analyses of lichens from different sampling sites suggest the presence of a relatively stable core microbiome and a sampling site-specific portion of the microbiome. Moreover, these studies indicate how the microbiota may contribute to the symbiotic system, to improve its health, growth and fitness.

Journal ArticleDOI
TL;DR: In this article, the authors reviewed and compared the current animal models of SARS-CoV-2 and found that the animal models were suitable for antiviral drug development and therapeutic effect evaluation.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus causing acute respiratory tract infection in humans. The virus has the characteristics of rapid transmission, long incubation period and strong pathogenicity, and has spread all over the world. Therefore, it is of great significance to select appropriate animal models for antiviral drug development and therapeutic effect evaluation. Here, we review and compare the current animal models of SARS-CoV-2.

Journal ArticleDOI
TL;DR: In this paper, the main advances in research on plant-pathogenic fungi in terms of their pathogenic factors such as cell wall-degrading enzymes, toxins, growth regulators, effector proteins, and fungal viruses, as well as their application as biocontrol agents for plant pests, diseases, and weeds.
Abstract: Phytopathogenic fungi decrease crop yield and quality and cause huge losses in agricultural production. To prevent the occurrence of crop diseases and insect pests, farmers have to use many synthetic chemical pesticides. The extensive use of these pesticides has resulted in a series of environmental and ecological problems, such as the increase in resistant weed populations, soil compaction, and water pollution, which seriously affect the sustainable development of agriculture. This review discusses the main advances in research on plant-pathogenic fungi in terms of their pathogenic factors such as cell wall-degrading enzymes, toxins, growth regulators, effector proteins, and fungal viruses, as well as their application as biocontrol agents for plant pests, diseases, and weeds. Finally, further studies on plant-pathogenic fungal resources with better biocontrol effects can help find new beneficial microbial resources that can control diseases.

Journal ArticleDOI
TL;DR: Garlic (Allium sativum), a popular food spice and flavoring agent, has also been used traditionally to treat various ailments especially bacterial infections for centuries in various cultures around the world as discussed by the authors.
Abstract: Garlic (Allium sativum), a popular food spice and flavoring agent, has also been used traditionally to treat various ailments especially bacterial infections for centuries in various cultures around the world. The principal phytochemicals that exhibit antibacterial activity are oil-soluble organosulfur compounds that include allicin, ajoenes, and allyl sulfides. The organosulfur compounds of garlic exhibit a range of antibacterial properties such as bactericidal, antibiofilm, antitoxin, and anti-quorum sensing activity against a wide range of bacteria including multi-drug resistant (MDR) strains. The reactive organosulfur compounds form disulfide bonds with free sulfhydryl groups of enzymes and compromise the integrity of the bacterial membrane. The World Health Organization (WHO) has recognized the development of antibiotic resistance as a global health concern and emphasizes antibiotic stewardship along with the urgent need to develop novel antibiotics. Multiple antibacterial effects of organosulfur compounds provide an excellent framework to develop them into novel antibiotics. The review provides a focused and comprehensive portrait of the status of garlic and its compounds as antibacterial agents. In addition, the emerging role of new technologies to harness the potential of garlic as a novel antibacterial agent is discussed.

Journal ArticleDOI
TL;DR: A review of virulence factors for hypervirulent Klebsiella pneumoniae (hvKP) can be found in this paper, where the authors summarize the most commonly used factors for survival and pathogenesis, including capsule, siderophores, lipopolysaccharide, fimbriae, outer membrane proteins, and type 6 secretion system.
Abstract: Hypervirulent Klebsiella pneumoniae (hvKP) has spread globally since first described in the Asian Pacific Rim. It is an invasive variant that differs from the classical K. pneumoniae (cKP), with hypermucoviscosity and hypervirulence, causing community-acquired infections, including pyogenic liver abscess, pneumonia, meningitis, and endophthalmitis. It utilizes a battery of virulence factors for survival and pathogenesis, such as capsule, siderophores, lipopolysaccharide, fimbriae, outer membrane proteins, and type 6 secretion system, of which the former two are dominant. This review summarizes these hvKP-associated virulence factors in order to understand its molecular pathogenesis and shed light on new strategies to improve the prevention, diagnosis, and treatment of hvKP-causing infection.

Journal ArticleDOI
TL;DR: It is shown that the production of GABA is regulated by pH, and that the GAD-system acts as a protective mechanism against acid stress in Bacteroides, mitigating cell death and preserving metabolic activity, and may represent the only amino acid-dependent acid tolerance system in Bactseroides.
Abstract: The high neuroactive potential of metabolites produced by gut microbes has gained traction over the last few years, with metagenomic-based studies suggesting an important role of microbiota-derived γ-aminobutyric acid (GABA) in modulating mental health. Emerging evidence has revealed the presence of the glutamate decarboxylase (GAD)-encoding gene, a key enzyme to produce GABA, in the prominent human intestinal genus Bacteroides. Here, we investigated GABA production by Bacteroides in culture and metabolic assays combined with comparative genomics and phylogenetics. A total of 961 Bacteroides genomes were analyzed in silico and 17 metabolically and genetically diverse human intestinal isolates representing 11 species were screened in vitro. Using the model organism Bacteroides thetaiotaomicron DSM 2079, we determined GABA production kinetics, its impact on milieu pH, and we assessed its role in mitigating acid-induced cellular damage. We showed that the GAD-system consists of at least four highly conserved genes encoding a GAD, a glutaminase, a glutamate/GABA antiporter, and a potassium channel. We demonstrated a high prevalence of the GAD-system among Bacteroides with 90% of all Bacteroides genomes (96% in human gut isolates only) harboring all genes of the GAD-system and 16 intestinal Bacteroides strains producing GABA in vitro (ranging from 0.09 to 60.84 mM). We identified glutamate and glutamine as precursors of GABA production, showed that the production is regulated by pH, and that the GAD-system acts as a protective mechanism against acid stress in Bacteroides, mitigating cell death and preserving metabolic activity. Our data also indicate that the GAD-system might represent the only amino acid-dependent acid tolerance system in Bacteroides. Altogether, our results suggest an important contribution of Bacteroides in the regulation of the GABAergic system in the human gut.

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TL;DR: In this article, the structural and functional changes of microbial community structure in the rhizospheric soil of sugarcane in different continuous cropping years using Illumina Miseq high-throughput sequencing and metagenomics analysis.
Abstract: The continuous cropping of plants can result in the disruption of the soil microbial community and caused significant declines in yields. However, there are few reports on the effects of continuous cropping of sugarcane on the microbial community structure and functional pathway. In the current study, we analyzed the structural and functional changes of microbial community structure in the rhizospheric soil of sugarcane in different continuous cropping years using Illumina Miseq high-throughput sequencing and metagenomics analysis. We collected rhizosphere soils from fields of no continuous cropping history (NCC), 10 years of continuous cropping (CC10), and 30 years of continuous cropping (CC30) periods in the Fujian province. The results demonstrated that continuous sugarcane cropping resulted in significant changes in the physicochemical properties of soil and the composition of soil bacterial and fungal communities. With the continuous cropping, the crop yield dramatically declined from NCC to CC30. Besides, the redundancy analysis (RDA) of the dominant bacterial and fungal phyla and soil physicochemical properties revealed that the structures of the bacterial and fungal communities were mainly driven by pH and TS. Analysis of potential functional pathways during the continuous cropping suggests that different KEGG pathways were enriched in different continuous cropping periods. The significant reduction of bacteria associated with rhizospheric soil nitrogen and sulfur cycling functions and enrichment of pathogenic bacteria may be responsible for the reduction of effective nitrogen and total sulfur content in rhizospheric soil of continuous sugarcane as well as the reduction of sugarcane yield and sugar content. Additionally, genes related to nitrogen and sulfur cycling were identified in our study, and the decreased abundance of nitrogen translocation genes and AprAB and DsrAB in the dissimilatory sulfate reduction pathway could be the cause of declined biomass. The findings of this study may provide a theoretical basis for uncovering the mechanism of obstacles in continuous sugarcane cropping and provide better guidance for sustainable development of the sugarcane.

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TL;DR: In this article, the authors used the funding support from CGLab/MoH======676 (General Laboratories Coordination of Brazilian Ministry of Health), CVSLR/FIOCRUZ (Coordination of Health Surveillance and Reference Laboratories of Oswaldo Cruz Foundation), CNPq======COVID-19 MCTI 402457/2020-0.
Abstract: We would like to thank the funding support from CGLab/MoH (General Laboratories Coordination of Brazilian Ministry of Health), CVSLR/FIOCRUZ (Coordination of Health Surveillance and Reference Laboratories of Oswaldo Cruz Foundation), CNPq COVID-19 MCTI 402457/2020-0, and INOVA VPPCB-005-FIO20-2

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TL;DR: In this paper, the most recent information on cellular components involved in OMV biogenesis, such as lipoproteins and outer membrane proteins, lipopolysaccharide, phospholipids, quorum-sensing molecules, and flagella, is presented.
Abstract: Outer membrane vesicles (OMVs) from Gram-negative bacteria were first described more than 50 years ago. However, the molecular mechanisms involved in biogenesis began to be studied only in the last few decades. Presently, the biogenesis and molecular mechanisms for their release are not completely known. This review covers the most recent information on cellular components involved in OMV biogenesis, such as lipoproteins and outer membrane proteins, lipopolysaccharide, phospholipids, quorum-sensing molecules, and flagella.

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TL;DR: The main role of Lactic acid bacteria (LAB) in wine is to conduct the malolactic fermentation (MLF), which can increase wine aroma and mouthfeel, improve microbial stability and reduce the acidity of wine.
Abstract: Currently, the main role of Lactic Acid Bacteria (LAB) in wine is to conduct the malolactic fermentation (MLF). This process can increase wine aroma and mouthfeel, improve microbial stability and reduce the acidity of wine. A growing number of studies support the appreciation that LAB can also significantly, positively and negatively, contribute to the sensorial profile of wine through many different enzymatic pathways. This is achieved either through the synthesis of compounds such as diacetyl and esters or by liberating bound aroma compounds such as glycoside-bound primary aromas and volatile thiols which are odorless in their bound form. LAB can also liberate hydroxycinnamic acids from their tartaric esters and have the potential to break down anthocyanin glucosides, thus impacting wine color. LAB can also produce enzymes with the potential to help in the winemaking process and contribute to stabilizing the final product. For example, LAB exhibit peptidolytic and proteolytic activity that could break down the proteins causing wine haze, potentially reducing the need for bentonite addition. Other potential contributions include pectinolytic activity, which could aid juice clarification and the ability to break down acetaldehyde, even when bound to SO2, reducing the need for SO2 additions during winemaking. Considering all these findings, this review summarizes the novel enzymatic activities of LAB that positively or negatively affect the quality of wine. Inoculation strategies, LAB improvement strategies, their potential to be used as targeted additions, and technological advances involving their use in wine are highlighted along with suggestions for future research.

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TL;DR: In this article, the authors provide a comprehensive examination of the in vitro and in vivo antimicrobial activities of different exopolysaccharides (EPSs), mainly against foodborne bacterial, fungal, and viral pathogens.
Abstract: Exopolysaccharides (EPSs) are metabolites synthesized and excreted by a variety of microorganisms, including lactic acid bacteria (LAB). EPS serve several biological functions such as interactions between bacteria and their environments, protection against hostile conditions including dehydration, the alleviation of the action of toxic compounds (bile salts, hydrolyzing enzymes, lysozyme, gastric, and pancreatic enzymes, metal ions, antibiotics), and stresses (changing pH, osmolarity), and evasion of the immune response and phage attack. Bacterial EPSs are considered valuable by the food, pharmaceutical, and nutraceutical industries, owing to their health-promoting benefits and rheological impacts. Numerous studies have reported the unusual antimicrobial activities of various EPS against a wide variety of pathogenic microbes (bacteria, virus, and fungi). This review aims to provide a comprehensive examination of the in vitro and in vivo antimicrobial activities of different EPSs, mainly against foodborne bacterial, fungal, and viral pathogens. The mechanism of EPS action against these pathogens as well as the methods used to measure antimicrobial activities are critically reviewed.

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TL;DR: In this article, a novel coating material derived from a catechol derivative, dopamine, known as polydopamine (PDA), has been designed and developed with the ability to adhere to almost all kinds of substrates.
Abstract: The drug resistance developed by bacteria during antibiotic treatment has been a call to action for researchers and scientists across the globe, as bacteria and fungi develop ever increasing resistance to current drugs. Innovative antimicrobial/antibacterial materials and coatings to combat such infections have become a priority, as many infections are caused by indwelling implants (e.g., catheters) as well as improving postsurgical function and outcomes. Pathogenic microorganisms that can exist either in planktonic form or as biofilms in water-carrying pipelines are one of the sources responsible for causing water-borne infections. To combat this, researchers have developed nanotextured surfaces with bactericidal properties mirroring the topographical features of some natural antibacterial materials. Protein-based adhesives, secreted by marine mussels, contain a catecholic amino acid, 3,4-dihydroxyphenylalanine (DOPA), which, in the presence of lysine amino acid, empowers with the ability to anchor them to various surfaces in both wet and saline habitats. Inspired by these features, a novel coating material derived from a catechol derivative, dopamine, known as polydopamine (PDA), has been designed and developed with the ability to adhere to almost all kinds of substrates. Looking at the immense potential of PDA, this review article offers an overview of the recent growth in the field of PDA and its derivatives, especially focusing the promising applications as antibacterial nanocoatings and discussing various antimicrobial mechanisms including reactive oxygen species-mediated antimicrobial properties.

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TL;DR: In this article, a comprehensive null-model approach quantified assembly mechanisms of floating and settled communities of anaerobic digestion for biological wastewater treatment is often underpinned by retaining millions of active granular biofilm aggregates, in particular highlighting the changing abundances of Methanosaeta and Lactococcus.
Abstract: Advances in null-model approaches have resulted in a deeper understanding of community assembly mechanisms for a variety of complex microbiomes. One under-explored application is assembly of communities from the built-environment, especially during process disturbances. Anaerobic digestion for biological wastewater treatment is often underpinned by retaining millions of active granular biofilm aggregates. Flotation of granules is a major problem, resulting in process failure. Anaerobic aggregates were sampled from three identical bioreactors treating dairy wastewater. Microbiome structure was analysed using qPCR and 16S rRNA gene amplicon sequencing from DNA and cDNA. A comprehensive null-model approach quantified assembly mechanisms of floating and settled communities. Significant differences in diversity were observed between floating and settled granules, in particular, we highlight the changing abundances of Methanosaeta and Lactococcus. Both stochastic and deterministic processes were important for community assembly. Homogeneous selection was the primary mechanism for all categories, but dispersal processes also contributed. The lottery model was used to identify clade-level competition driving community assembly. Lottery ‘winners’ were identified with different winners between floating and settled groups. Some groups changed their winner status when flotation occurred. Spirochaetaceae, for example, was only a winner in settled biomass (cDNA-level) and lost its winner status during flotation. Alternatively, Arcobacter butzerli gained winner status during flotation. This analysis provides a deeper understanding of changes that occur during process instabilities and identified groups which may be washed out – an important consideration for process control.

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TL;DR: In this paper, different repurposed drugs, including chloroquine phosphate, chloroquines, hydroxychloroquine, ivermectin, remdesivir and favipiravir, were screened in the present study and molecular docking of these drugs with different SARS-CoV-2 target proteins, including spike and membrane proteins, RdRp, nucleoproteins, viral proteases and nsp14, was performed.
Abstract: SARS-CoV-2 is a newly emerged coronavirus that causes a respiratory disease with variable severity and fatal consequences. It was first reported in Wuhan and subsequently caused a global pandemic. The viral spike protein binds with the ACE-2 cell surface receptor for entry, while TMPRSS2 triggers its membrane fusion. RNA‐dependent RNA polymerase (RdRp), viral proteases and M proteins are important in different stages of viral replication. Accordingly, they are attractive targets for different antiviral therapeutic agents. Although many antiviral agents have been used in different clinical trials and included in different treatment protocols, the mode of action against SARS-CoV-2 is still not fully understood. Different potential repurposed drugs, including chloroquine phosphate, chloroquine, hydroxychloroquine, ivermectin, remdesivir and favipiravir, were screened in the present study. Molecular docking of these drugs with different SARS-CoV-2 target proteins, including spike and membrane proteins, RdRp, nucleoproteins, viral proteases and nonstructural protein 14 (nsp14), was performed. Moreover, the binding affinities of the human ACE-2 receptor and TMPRSS2 to the different drugs were evaluated. Molecular dynamics simulation and MM-PBSA calculation were also conducted. Ivermectin and remdesivir were found to be the most promising drugs. Our results suggest that both these drugs utilise different mechanisms at the entry and post-entry stages and could be considered potential inhibitors of SARS‐CoV‐2 replication.