Transition from Hashimoto thyroiditis to Graves's Disease: an unpredictable change?

PURPOSE: Hashimoto thyroiditis and Graves's disease are two related autoimmune disorders, representing the leading causes of hypothyroidism and hyperthyroidism. Autoimmune hypothyroidism is generally irreversible but very rarely, some patients would shift to hyperthyroidism. The aim of the study was to seek for possible clinical predictors of the transition from hypo to hyperthyroidism in patients with Hashimoto thyroiditis and to outline their clinical phenotype. METHODS: Twelve patients with overt autoimmune hypothyroidism who had at least one transition from hypothyroidism to autoimmune hyperthyroidism were compared with 294 consecutive patients with autoimmune hypothyroidism and 69 consecutive patients with autoimmune hyperthyroidism that accessed the outpatient clinic over six months. Demographic, hormonal data and autoantibodies titers were compared. RESULTS: Prevalence of smoking habit was significantly higher in switchers compared to controls. Switchers showed a significantly higher prevalence of personal and familial history of non-thyroidal autoimmune disorders. TSH levels were significantly lower in the switcher group during the hypothyroid phase and levothyroxine dose required was lower. TSH concentrations were significantly lower while free fT4 and free fT3 values were higher in GD patients compared to switchers during the hyperthyroid phase despite comparable TRAb levels. Prevalence and type of hyperthyroid symptoms and orbitopathy were similar between switchers and GD group. Mean dose of anti-thyroid drugs was significantly higher in GD patients compared to switchers. No differences were observed in the remission rate from hyperthyroidism between the two groups, despite switchers showed a significantly lower time-to-remission. CONCLUSIONS: Conversion of Hashimoto Thyroiditis towards Graves' disease is a rare phenomenon which can occur almost at any time after the development of autoimmune hypothyroidism. Our findings suggest active surveillance of hypothyroid patients who require frequent reduction of levothyroxine during follow up and testing for TSHR antibodies in these patients.

Hydrocarbon degradation strategy and pyoverdine production using the salt tolerant Antarctic bacterium Marinomonas sp. ef1.

One of the most concerning environmental problems is represented by petroleum and its derivatives causing contamination of aquatic and underground environments. In this work, the degradation treatment of diesel using Antarctic bacteria is proposed. Marinomonas sp. ef1 is a bacterial strain isolated from a consortium associated with the Antarctic marine ciliate Euplotes focardii. Its potential in the degradation of hydrocarbons commonly present in diesel oil were studied. The bacterial growth was evaluated in culturing conditions that resembled the marine environment with 1% (v/v) of either diesel or biodiesel added; in both cases, Marinomonas sp. ef1 was able to grow. The chemical oxygen demand measured after the incubation of bacteria with diesel decreased, demonstrating the ability of bacteria to use diesel hydrocarbons as a carbon source and degrade them. The metabolic potential of Marinomonas to degrade aromatic compounds was supported by the identification in the genome of sequences encoding various enzymes involved in benzene and naphthalene degradation. Moreover, in the presence of biodiesel, a fluorescent yellow pigment was produced; this was isolated, purified and characterized by UV-vis and fluorescence spectroscopy, leading to its identification as a pyoverdine. These results suggest that Marinomonas sp. ef1 can be used in hydrocarbon bioremediation and in the transformation of these pollutants in molecules of interest.

Mimicking the last step of gene elongation: hints from the bacterial hisF gene.

Gene elongation consists in an in-tandem duplication of a gene and divergence and fusion of the two copies, resulting in a gene constituted by two divergent paralogous modules. Many present-day proteins show internal repeats of amino acid sequences, generated by gene elongation events; however, gene elongation is still a poorly studied evolutionary molecular mechanism. The most documented case is that of the histidine biosynthetic genes hisA and hisF, which derive from the gene elongation of an ancestral gene half the size of the extant ones. The aim of this work was to experimentally simulate the possible last step of the gene elongation event occurred during hisF gene evolution under selective pressure conditions. Azospirillum brasilense hisF gene, carrying a single nucleotide mutation that generates a stop codon between the two halves of the gene, was used to transform the histidine-auxotrophic Escherichia coli strain FB182 (hisF892). The transformed strain was subjected to selective pressure (i.e., low concentration/absence of histidine in the growth medium) and the obtained mutants were characterized. The restoration of prototrophy was strongly dependent on the time of incubation and on the strength of the selective pressure. The mutations involved the introduced stop codon with a single base substitution and none of the mutants restored the wild-type codon. Possible correlations between the different mutations and i) E. coli codon usage, ii) three-dimensional structures of the mutated HisF proteins, and iii) growth ability of the mutants were investigated. On the contrary, when the experiment was repeated by mutating a more conserved codon, only a synonymous substitution was obtained. Thus, experiments performed in this study allowed to mimic a possible gene elongation event occurred during the evolution of hisF gene, evidencing the ability of bacterial cells to modify their genome in short times under selective conditions.

Adaptation of Commensal Escherichia coli in Tomato Fruits: Motility, Stress, Virulence.

Food contamination can be a serious concern for public health because it can be related to the severe spreading of pathogens. This is a main issue, especially in the case of fresh fruits and vegetables; indeed, they have often been associated with gastrointestinal outbreak events, due to contamination with pathogenic bacteria. However, little is known about the physiological adaptation and bacterial response to stresses encountered in the host plant. Thus, this work aimed to investigate the adaptation of a commensal E. coli strain while growing in tomato pericarp. Pre-adapted and non-adapted cells were compared and used to contaminate tomatoes, demonstrating that pre-adaptation boosted cell proliferation. DNA extracted from pre-adapted and non-adapted cells was sequenced, and their methylation profiles were compared. Hence, genes involved in cell adhesion and resistance against toxic compounds were identified as genes involved in adaptation, and their expression was compared in these two experimental conditions. Finally, pre-adapted and non-adapted E. coli were tested for their ability to resist the presence of toxic compounds, demonstrating that adaptation exerted a protective effect. In conclusion, this work provides new information about the physiological adaptation of bacteria colonizing the tomato fruit pericarp.

Novel Sources of Biodiversity and Biomolecules from Bacteria Isolated from a High Middle Ages Soil Sample in Palermo (Sicily, Italy).

The urban plan of Palermo (Sicily, Italy) has evolved throughout Punic, Roman, Byzantine, Arab, and Norman ages until it stabilized within the borders that correspond to the current historic center. During the 2012 to 2013 excavation campaign, new remains of the Arab settlement, directly implanted above the structures of the Roman age, were found. The materials investigated in this study derived from the so-called Survey No 3, which consists of a rock cavity of subcylindrical shape covered with calcarenite blocks: it was probably used to dispose of garbage during the Arabic age and its content, derived from daily activities, included grape seeds, scales and bones of fish, small animal bones, and charcoals. Radiocarbon dating confirmed the medieval origin of this site. The composition of the bacterial community was characterized through a culture-dependent and a culture-independent approach. Culturable bacteria were isolated under aerobic and anaerobic conditions and the total bacterial community was characterized through metagenomic sequencing. Bacterial isolates were tested for the production of compounds with antibiotic activity: a Streptomyces strain, whose genome was sequenced, was of particular interest because of its inhibitory activity, which was due to the Type I polyketide aureothin. Moreover, all strains were tested for the production of secreted proteases, with those belonging to the genus Nocardioides having the most active enzymes. Finally, protocols commonly used for ancient DNA studies were applied to evaluate the antiquity of isolated bacterial strains. Altogether these results show how paleomicrobiology might represent an innovative and unexplored source of novel biodiversity and new biotechnological tools. IMPORTANCE One of the goals of paleomicrobiology is the characterization of the microbial community present in archaeological sites. These analyses can usually provide valuable information about past events, such as occurrence of human and animal infectious diseases, ancient human activities, and environmental changes. However, in this work, investigations about the composition of the bacterial community of an ancient soil sample (harvested in Palermo, Italy) were carried out aiming to screen ancient culturable strains with biotechnological potential, such as the ability to produce bioactive molecules and secreted hydrolytic enzymes. Besides showing the biotechnological relevance of paleomicrobiology, this work reports a case of germination of putatively ancient bacterial spores recovered from soil rather than extreme environments. Moreover, in the case of spore-forming species, these results raise questions about the accuracy of techniques usually applied to estimate antiquity of DNA, as they could lead to its underestimation.

Genomic, Molecular, and Phenotypic Characterization of Arthrobacter sp. OVS8, an Endophytic Bacterium Isolated from and Contributing to the Bioactive Compound Content of the Essential Oil of the Medicinal Plant Origanum vulgare L.

Medicinal plants play an important role in the discovery of new bioactive compounds with antimicrobial activity, thanks to their pharmacological properties. However, members of their microbiota can also synthesize bioactive molecules. Among these, strains belonging to the genera Arthrobacter are commonly found associated with the plant's microenvironments, showing plant growth-promoting (PGP) activity and bioremediation properties. However, their role as antimicrobial secondary metabolite producers has not been fully explored. The aim of this work was to characterize the Arthrobacter sp. OVS8 endophytic strain, isolated from the medicinal plant Origanum vulgare L., from molecular and phenotypic viewpoints to evaluate its adaptation and influence on the plant internal microenvironments and its potential as a producer of antibacterial volatile molecules (VOCs). Results obtained from the phenotypic and genomic characterization highlight its ability to produce volatile antimicrobials effective against multidrug-resistant (MDR) human pathogens and its putative PGP role as a producer of siderophores and degrader of organic and inorganic pollutants. The outcomes presented in this work identify Arthrobacter sp. OVS8 as an excellent starting point toward the exploitation of bacterial endophytes as antibiotics sources.

Application of Cloning-Free Genome Engineering to Escherichia coli.

The propagation of foreign DNA in Escherichia coli is central to molecular biology. Recent advances have dramatically expanded the ability to engineer (bacterial) cells; however, most of these techniques remain time-consuming. The aim of the present work was to explore the possibility to use the cloning-free genome editing (CFGE) approach, proposed by Döhlemann and coworkers (2016), for E. coli genetics, and to deepen the knowledge about the homologous recombination mechanism. The E. coli auxotrophic mutant strains FB182 (hisF892) and FB181 (hisI903) were transformed with the circularized wild-type E. coli (i) hisF gene and hisF gene fragments of decreasing length, and (ii) hisIE gene, respectively. His+ clones were selected based on their ability to grow in the absence of histidine, and their hisF/hisIE gene sequences were characterized. CFGE method allowed the recombination of wild-type his genes (or fragments of them) within the mutated chromosomal copy, with a different recombination frequency based on the fragment length, and the generation of clones with a variable number of in tandem his genes copies. Data obtained pave the way to further evolutionary studies concerning the homologous recombination mechanism and the fate of in tandem duplicated genes.

Effect of Wastewater on the Composition of Bacterial Microbiota of Phragmites australis Used in Constructed Wetlands for Phytodepuration.

Phytodepuration occurs in the plant-mediated remediation processes exploited to remove pollutants from wastewater, and Phragmites australis is one of the most used plants. This goal is achieved using constructed wetlands (CW), which are engineered systems designed to mimic the natural processes of pollutants removal. The aim of this work was to characterize the bacterial communities associated to P. australis, soils, and permeates of the CW of Calice (Prato, Italy), to evaluate the possible effect of wastewaters on the CW bacterial communities, through a next-generation sequencing-based approach. A total of 122 samples were collected from different tissues of P. australis (i.e., roots, aerial parts, and stem), soil (i.e., rhizospheric and bulk soil), and permeates, and analyzed. All samples were collected during five sampling campaigns, with the first one performed before the activation of the plant. Obtained results highlighted a specific microbiota of P. australis, conserved among the different plant tissues and during time, showing a lower alpha diversity than the other samples and not influenced by the more complex and variable environmental (soils and permeates) bacterial communities. These data suggest that P. australis is able to select and maintain a defined microbiota, a capacity that could allow the plant to survive in hostile environments, such as that of CW.

Unravelling the DNA sequences carried by Streptomyces coelicolor membrane vesicles.

Membrane vesicles (MVs) are spherical particles with nanoscale dimensions and characterized by the presence of diverse cargos, such as nucleic acids, proteins, lipids, and cellular metabolites. Many examples of (micro)organisms producing MVs are reported in literature. Among them, bacterial MVs are of particular interest because they are now considered as the fourth mechanism of horizontal gene transfer. Streptomyces bacteria are well-known for their ecological roles and ability to synthesize bioactive compounds, with Streptomyces coelicolor being the model organism. It was previously demonstrated that it can produce distinct populations of MVs characterized by different protein and metabolite cargos. In this work we demonstrated for the first time that MVs of S. coelicolor carry both DNA and RNA and that their DNA content represents the entire chromosome of the bacterium. These findings suggest that MV DNA could have a role in the evolution of Streptomyces genomes and that MVs could be exploited in new strain engineering strategies.

Distinct Clinical Features of Post-COVID-19 Vaccination Early-onset Graves' Disease.

CONTEXT: Several case reports of Graves' disease (GD) occurrence after COVID-19 vaccination that are possibly related to the autoimmune syndrome induced by adjuvants (ASIA) were published recently. OBJECTIVE: The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021. METHODS: Patients with a first episode of GD attending a tertiary endocrine center between January 1, 2021, and December 31, 2021, were included. RESULTS: Sixty-four patients with a first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared with the other 44 patients, the 20 patients with postvaccine early-onset (PoVEO) GD were older (median age 51 years vs 35 years, P = .003) and more likely to be male (40.0% vs 13.6%, P = .018). At diagnosis, the biochemical and immune profiles were similar between the 2 groups. However, at 3 months after starting methimazole, patients with PoVEO GD had significantly lower thyrotropin receptor antibody titer and were taking lower doses of methimazole than the other patients with GD. None in the PoVEO group had sustained free triiodothyronine elevation. CONCLUSION: This relatively large series suggests that in 2021 PoVEO GD may be a new nosologic entity representing one-third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence, and a better initial biochemical and immunologic response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurring GD.

Microbial Genetics and Evolution.

Although proto-evolutionary ideas date back to the time of the ancient Greeks, the idea that organisms evolve was not considered a basic element of scientific knowledge until Charles Darwin published his "On the Origin of Species" in 1859 [...].

Endophytic Bacteria and Essential Oil from Origanum vulgare ssp. vulgare Share Some VOCs with an Antibacterial Activity.

Medicinal aromatic plants' essential oils (EOs) are mixtures of volatile compounds showing antimicrobial activity, which could be exploited to face the emerging problem of multi-drug resistance. Their chemical composition can depend on the interactions between the plant and its endophytic microbiota, which is known to synthesize volatile organic compounds (VOCs). However, it is still not clear whether those volatile metabolites can contribute to the composition of the aroma profile of plants' EOs. The aims of this study were to characterize medicinal plant O. vulgare ssp. vulgare bacterial endophyte VOCs, evaluating their ability to antagonize the growth of opportunistic human pathogens belonging to the Burkholderia cepacia complex (Bcc) and compare them with O. vulgare EO composition. Many of the tested endophytic strains showed (i) a bactericidal and/or bacteriostatic activity against most of Bcc strains and (ii) the production of VOCs with widely recognized antimicrobial properties, such as dimethyl disulfide, dimethyl trisulfide, and monoterpenes. Moreover, these monoterpenes were also detected in the EOs extracted from the same O. vulgare plants from which endophytes were isolated. Obtained results suggest that endophytes could also play a role in the antibacterial properties of O. vulgare ssp. vulgare and, potentially, in determining its aromatic composition.

Genomic Analysis of Endophytic Bacillus-Related Strains Isolated from the Medicinal Plant Origanum vulgare L. Revealed the Presence of Metabolic Pathways Involved in the Biosynthesis of Bioactive Compounds.

Multidrug-resistant pathogens represent a serious threat to human health. The inefficacy of traditional antibiotic drugs could be surmounted through the exploitation of natural bioactive compounds of which medicinal plants are a great reservoir. The finding that bacteria living inside plant tissues, (i.e., the endophytic bacterial microbiome) can influence the synthesis of the aforementioned compounds leads to the necessity of unraveling the mechanisms involved in the determination of this symbiotic relationship. Here, we report the genome sequence of four endophytic bacterial strains isolated from the medicinal plant Origanum vulgare L. and able to antagonize the growth of opportunistic pathogens of cystic fibrosis patients. The in silico analysis revealed the presence of gene clusters involved in the production of antimicrobial compounds, such as paeninodin, paenilarvins, polymyxin, and paenicidin A. Endophytes' adaptation to the plant microenvironment was evaluated through the analysis of the presence of antibiotic resistance genes in the four genomes. The diesel fuel degrading potential was also tested. Strains grew in minimum media supplemented with diesel fuel, but no n-alkanes degradation genes were found in their genomes, suggesting that diesel fuel degradation might occur through other steps involving enzymes catalyzing the oxidation of aromatic compounds.

The Bacterial Urban Resistome: Recent Advances.

Cities that are densely populated are reservoirs of antibiotic resistant genes (ARGs). The overall presence of all resistance genes in a specific environment is defined as a resistome. Spatial proximity of surfaces and different hygienic conditions leads to the transfer of antibiotic resistant bacteria (ARB) within urban environments. Built environments, public transportation, green spaces, and citizens' behaviors all support persistence and transfer of antimicrobial resistances (AMR). Various unique aspects of urban settings that promote spread and resilience of ARGs/ARB are discussed: (i) the role of hospitals and recreational parks as reservoirs; (ii) private and public transportation as carriers of ARGs/ARB; (iii) the role of built environments as a hub for horizontal gene transfer even though they support lower microbial biodiversity than outdoor environments; (iv) the need to employ ecological and evolutionary concepts, such as modeling the fate of a specific ARG/ARB, to gain enhanced health risk assessments. Our understanding and our ability to control the rise of AMR in an urban setting is linked to our knowledge of the network connecting urban reservoirs and the environment.

Streptomyces coelicolor Vesicles: Many Molecules To Be Delivered.

Streptomyces coelicolor is a model organism for the study of Streptomyces, a genus of Gram-positive bacteria that undergoes a complex life cycle and produces a broad repertoire of bioactive metabolites and extracellular enzymes. This study investigated the production and characterization of membrane vesicles (MVs) in liquid cultures of S. coelicolor M145 from a structural and biochemical point of view; this was achieved by combining microscopic, physical and -omics analyses. Two main populations of MVs, with different sizes and cargos, were isolated and purified. S. coelicolor MV cargo was determined to be complex, containing different kinds of proteins and metabolites. In particular, a total of 166 proteins involved in cell metabolism/differentiation, molecular processing/transport, and stress response were identified in MVs, the latter functional class also being important for bacterial morpho-physiological differentiation. A subset of these proteins was protected from degradation following treatment of MVs with proteinase K, indicating their localization inside the vesicles. Moreover, S. coelicolor MVs contained an array of metabolites, such as antibiotics, vitamins, amino acids, and components of carbon metabolism. In conclusion, this analysis provides detailed information on S. coelicolor MVs under basal conditions and on their corresponding content, which may be useful in the near future to elucidate vesicle biogenesis and functions. IMPORTANCE Streptomycetes are widely distributed in nature and characterized by a complex life cycle that involves morphological differentiation. They are very relevant in industry because they produce about half of all clinically used antibiotics, as well as other important pharmaceutical products of natural origin. Streptomyces coelicolor is a model organism for the study of bacterial differentiation and bioactive molecule production. S. coelicolor produces extracellular vesicles that carry many molecules, such as proteins and metabolites, including antibiotics. The elucidation of S. coelicolor extracellular vesicle cargo will help us to understand different aspects of streptomycete physiology, such as cell communication during differentiation and response to environmental stimuli. Moreover, the capability of these vesicles for carrying different kinds of biomolecules opens up new biotechnological possibilities related to drug delivery. Indeed, decoding the molecular mechanisms involved in cargo selection may lead to the customization of extracellular vesicle content.

Educational Activities for Students and Citizens Supporting the One-Health Approach on Antimicrobial Resistance.

Antibiotic resistance is one of the biggest threats to global health, food security and development. Urgent action is needed at all levels of society to reduce the impact and spread of antibiotic resistance. For a more sustaining approach, education in children, college students, citizens and caregivers are essential. The One-Heath approach is a collaborative, multisectoral and transdisciplinary strategy in which, no single organizations or sector can address the issue of antimicrobial resistance at the human-environment interface alone. Within this strategy, education plays a central role. In this scoping review, we highlighted a range of learning activities on antibiotic resistance as part of the One-Health approach. In particular, those applications that can be introduced to a wide audience to help arrest the current crisis for the next generation. The review identifies a high number of teaching opportunities: board and role-play games, round tables, musicals, e-learning and environmental experiments to couple with more curricula and formal education to inform a diverse group of audiences.

Antibiotic-Resistant Genes and Bacteria as Evolving Contaminants of Emerging Concerns (e-CEC): Is It Time to Include Evolution in Risk Assessment?

The pressing issue of the abundance of antibiotic resistance genes and resistant bacteria in the environment (ARGs and ARB, respectively) requires procedures for assessing the risk to health. The chemo-centric environmental risk assessment models identify hazard(s) in a dose-response manner, obtaining exposure, toxicity, risk, impact and policy. However, this risk assessment approach based on ARGs/ARB evaluation from a quantitative viewpoint shows high unpredictability because ARGs/ARB cannot be considered as standard hazardous molecules: ARB duplicate and ARGs evolve within a biological host. ARGs/ARB are currently listed as Contaminants of Emerging Concern (CEC). In light of such characteristics, we propose to define ARGs/ARB within a new category of evolving CEC (or e-CEC). ARGs/ARB, like any other evolving determinants (e.g., viruses, bacteria, genes), escape environmental controls. When they do so, just one molecule left remaining at a control point can form the origin of a new dangerous and selection-responsive population. As a consequence, perhaps it is time to acknowledge this trait and to include evolutionary concepts within modern risk assessment of e-CEC. In this perspective we analyze the evolutionary responses most likely to influence risk assessment, and we speculate on the means by which current methods could measure evolution. Further work is required to implement and exploit such experimental procedures in future risk assessment protocols.

The Histidine Biosynthetic Genes in the Superphylum Bacteroidota-Rhodothermota-Balneolota-Chlorobiota: Insights into the Evolution of Gene Structure and Organization.

One of the most studied metabolic routes is the biosynthesis of histidine, especially in enterobacteria where a single compact operon composed of eight adjacent genes encodes the complete set of biosynthetic enzymes. It is still not clear how his genes were organized in the genome of the last universal common ancestor community. The aim of this work was to analyze the structure, organization, phylogenetic distribution, and degree of horizontal gene transfer (HGT) of his genes in the Bacteroidota-Rhodothermota-Balneolota-Chlorobiota superphylum, a group of phylogenetically close bacteria with different surviving strategies. The analysis of the large variety of his gene structures and organizations revealed different scenarios with genes organized in more or less compact-heterogeneous or homogeneous-operons, in suboperons, or in regulons. The organization of his genes in the extant members of the superphylum suggests that in the common ancestor of this group, genes were scattered throughout the chromosome and that different forces have driven the assembly of his genes in compact operons. Gene fusion events and/or paralog formation, HGT of single genes or entire operons between strains of the same or different taxonomic groups, and other molecular rearrangements shaped the his gene structure in this superphylum.

Antibacterial activity of bacteria isolated from Phragmites australis against multidrug-resistant human pathogens.

Background: Rising number of multidrug-resistant human pathogens demands novel antibiotics: to this aim, unexplored natural sources are investigated to find new compounds. In this context, bacteria associated to medicinal plants, including Phragmites australis, might represent an important source of antimicrobial compounds. Materials & methods: In the present work, 21 bacterial endophytes isolated from P. australis roots were tested, by cross-streaking, for their inhibitory activity against 36 multidrug-resistant pathogens isolated from food, clinical patients and hospitals. Results & conclusion: Seven endophytes, belonging to Pseudomonas and Stenotrophomonas, were able to inhibit the growth of most of the target strains. In conclusion, this preliminary work could pave the way for the discovery of new antibiotics against superbugs.

Lay abstract In the present work, 21 bacteria associated to Phragmites australis roots were tested for their inhibitory activity against 36 human pathogens isolated from food, clinical patients and/or hospitals, which have the ability to escape several commonly used antibiotics. Seven out of 21 bacteria associated to P. australis were able to inhibit the growth of most of target pathogens. This preliminary work could pave the way to the discovery of new antimicrobial compounds active against bacterial pathogens that cannot be killed using several antibiotics.

Medicinal Plants and Their Bacterial Microbiota: A Review on Antimicrobial Compounds Production for Plant and Human Health.

Medicinal plants (MPs) have been used since antiquity in traditional and popular medicine, and they represent a very important source of bioactive molecules, including antibiotic, antiviral, and antifungal molecules. Such compounds are often of plant origin, but in some cases, an origin or a modification from plant microbiota has been shown. Actually, the research continues to report the production of bioactive molecules by plants, but the role of plant-endophytic interaction is emerging. Classic examples are mainly concerned with fungal endophytes; however, it has been recently shown that bacterial endophytes can also play an important role in influencing the plant metabolism related to the synthesis of bioactive compounds. In spite of this, a deep investigation on the power of MP bacterial endophytes is lacking. Here, an overview of the studies on MP bacterial microbiota and its role in the production of plant antimicrobial compounds contributing to prime host defense system and representing a huge resource for biotech and therapeutic applications is provided.