Gut microbiome encoded purine and amino acid pathways present prospective biomarkers for predicting metformin therapy efficacy in newly diagnosed T2D patients.

Metformin is widely used for treating type 2 diabetes mellitus (T2D). However, the efficacy of metformin monotherapy is highly variable within the human population. Understanding the potential indirect or synergistic effects of metformin on gut microbiota composition and encoded functions could potentially offer new insights into predicting treatment efficacy and designing more personalized treatments in the future. We combined targeted metabolomics and metagenomic profiling of gut microbiomes in newly diagnosed T2D patients before and after metformin therapy to identify potential pre-treatment biomarkers and functional signatures for metformin efficacy and induced changes in metformin therapy responders. Our sequencing data were largely corroborated by our metabolic profiling and identified that pre-treatment enrichment of gut microbial functions encoding purine degradation and glutamate biosynthesis was associated with good therapy response. Furthermore, we identified changes in glutamine-associated amino acid (arginine, ornithine, putrescine) metabolism that characterize differences in metformin efficacy before and after the therapy. Moreover, metformin Responders' microbiota displayed a shifted balance between bacterial lipidA synthesis and degradation as well as alterations in glutamate-dependent metabolism of N-acetyl-galactosamine and its derivatives (e.g. CMP-pseudaminate) which suggest potential modulation of bacterial cell walls and human gut barrier, thus mediating changes in microbiome composition. Together, our data suggest that glutamine and associated amino acid metabolism as well as purine degradation products may potentially condition metformin activity via its multiple effects on microbiome functional composition and therefore serve as important biomarkers for predicting metformin efficacy.

Mold Fungal Resistance of Loose-Fill Thermal Insulation Materials Based on Processed Wheat Straw, Corn Stalk and Reed.

The present study evaluates the mold fungal resistance of newly developed loose-fill thermal insulation materials made of wheat straw, corn stalk and water reed. Three distinct techniques for the processing of raw materials were used: mechanical crushing (Raw, ≤20 mm), thermo-mechanical pulping (TMP) with 4% NaOH and steam explosion pulping (SEP). An admixture of boric acid (8%) and tetraborate (7%) was applied to all processed substrates due to their anti-fungal properties. The fourth sample group was prepared from SEP substrates without added fungicide (SEP*) as control. Samples from all treatments were separately inoculated by five different fungal species and incubated in darkness for 28 days at 28 °C and RH > 90%. The highest resistance to the colonization of mold fungi was achieved by TMP and SEP processing, coupled with the addition of boric acid and tetraborate, where molds infested only around 35% to 40% of the inoculated sample area. The lowest mold fungi resistance was detected for the Raw and SEP* samples, each ~75%; they were affected by rich amount of accessible nutrients, suggesting that boric acid and tetraborate additives alone did not prevent mold fungal growth as effectively as in combination with TMP and SEP treatments. Together, the achieved fungal colonization scores after combined fungicide and pulping treatments are very promising for the application of tested renewable materials in the future development of thermal insulation products.

Pieris brassicae eggs trigger interplant systemic acquired resistance against a foliar pathogen in Arabidopsis.

Recognition of plant pathogens or herbivores activate a broad-spectrum plant defense priming in distal leaves against potential future attacks, leading to systemic acquired resistance (SAR). Additionally, attacked plants can release aerial or below-ground signals that trigger defense responses, such as SAR, in neighboring plants lacking initial exposure to pathogen or pest elicitors. However, the molecular mechanisms involved in interplant defense signal generation in sender plants and decoding in neighboring plants are not fully understood. We previously reported that Pieris brassicae eggs induce intraplant SAR against the foliar pathogen Pseudomonas syringae in Arabidopsis thaliana. Here we extend this effect to neighboring plants by discovering an egg-induced interplant SAR via mobile root-derived signal(s). The generation of an egg-induced interplant SAR signal requires pipecolic acid (Pip) pathway genes ALD1 and FMO1 but occurs independently of salicylic acid (SA) accumulation in sender plants. Furthermore, reception of the signal leads to accumulation of SA in the recipient plants. In response to insect eggs, plants may induce interplant SAR to prepare for potential pathogen invasion following feeding-induced wounding or to keep neighboring plants healthy for hatching larvae. Our results highlight a previously uncharacterized below-ground plant-to-plant signaling mechanism and reveals genetic components required for its generation.

A few sequence polymorphisms among isolates of Maize bushy stunt phytoplasma associate with organ proliferation symptoms of infected maize plants.

Background and Aims: Maize bushy stunt phytoplasma (MBSP) is a bacterial pathogen of maize ( Zea mays L.) across Latin America. MBSP belongs to the 16SrI-B sub-group within the genus ' Candidatus Phytoplasma'. MBSP and its insect vector Dalbulus maidis (Hemiptera: Cicadellidae) are restricted to maize; both are thought to have coevolved with maize during its domestication from a teosinte-like ancestor. MBSP-infected maize plants show a diversity of symptoms. and it is likely that MBSP is under strong selection for increased virulence and insect transmission on maize hybrids that are widely grown in Brazil. In this study it was investigated whether the differences in genome sequences of MBSP isolates from two maize-growing regions in South-east Brazil explain variations in symptom severity of the MBSP isolates on various maize genotypes. Methods: MBSP isolates were collected from maize production fields in Guaíra and Piracicaba in South-east Brazil for infection assays. One representative isolate was chosen for de novo whole-genome assembly and for the alignment of sequence reads from the genomes of other phytoplasma isolates to detect polymorphisms. Statistical methods were applied to investigate the correlation between variations in disease symptoms of infected maize plants and MBSP sequence polymorphisms. Key Results: MBSP isolates contributed consistently to organ proliferation symptoms and maize genotype to leaf necrosis, reddening and yellowing of infected maize plants. The symptom differences are associated with polymorphisms in a phase-variable lipoprotein, which is a candidate effector, and an ATP-dependent lipoprotein ABC export protein, whereas no polymorphisms were observed in other candidate effector genes. Lipoproteins and ABC export proteins activate host defence responses, regulate pathogen attachment to host cells and activate effector secretion systems in other pathogens. Conclusions: Polymorphisms in two putative virulence genes among MBSP isolates from maize-growing regions in South-east Brazil are associated with variations in organ proliferation symptoms of MBSP-infected maize plants.

A Bacterial Parasite Effector Mediates Insect Vector Attraction in Host Plants Independently of Developmental Changes.

Parasites can take over their hosts and trigger dramatic changes in host appearance and behavior that are typically interpreted as extended phenotypes that promote parasite survival and fitness. For example, Toxoplasma gondii is thought to manipulate the behaviors of infected rodents to aid transmission to cats and parasitic trematodes of the genus Ribeiroia alter limb development in their amphibian hosts to facilitate predation of the latter by birds. Plant parasites and pathogens also reprogram host development and morphology. However, whereas some parasite-induced morphological alterations may have a direct benefit to the fitness of the parasite and may therefore be adaptive, other host alterations may be side effects of parasite infections having no adaptive effects on parasite fitness. Phytoplasma parasites of plants often induce the development of leaf-like flowers (phyllody) in their host plants, and we previously found that the phytoplasma effector SAP54 generates these leaf-like flowers via the degradation of plant MADS-box transcription factors (MTFs), which regulate all major aspects of development in plants. Leafhoppers prefer to reproduce on phytoplasma-infected and SAP54-trangenic plants leading to the hypothesis that leafhopper vectors are attracted to plants with leaf-like flowers. Surprisingly, here we show that leafhopper attraction occurs independently of the presence of leaf-like flowers. First, the leafhoppers were also attracted to SAP54 transgenic plants without leaf-like flowers and to single leaves of these plants. Moreover, leafhoppers were not attracted to leaf-like flowers of MTF-mutant plants without the presence of SAP54. Thus, the primary role of SAP54 is to attract leafhopper vectors, which spread the phytoplasmas, and the generation of leaf-like flowers may be secondary or a side effect of the SAP54-mediated degradation of MTFs.

Insect-borne plant pathogenic bacteria: getting a ride goes beyond physical contact.

Plant pathogens have evolved numerous strategies that enable their movement from plant to plant. Phytopathogens use a great variety of insect species for transmission to plants, and insect transmission has evolved multiple times independently, particularly for phloem-inhabiting bacteria. Recent studies have advanced our understanding about the mechanisms of physical association between plant pathogenic bacteria and insect vectors. Furthermore, recent evidence shows that the transmission of plant pathogens goes beyond a physical association with the insect, and involves active modulation of plant processes by the bacteria to promote insect herbivore attraction, colonization and pathogen transmission.

Phytoplasma effector SAP54 hijacks plant reproduction by degrading MADS-box proteins and promotes insect colonization in a RAD23-dependent manner.

Pathogens that rely upon multiple hosts to complete their life cycles often modify behavior and development of these hosts to coerce them into improving pathogen fitness. However, few studies describe mechanisms underlying host coercion. In this study, we elucidate the mechanism by which an insect-transmitted pathogen of plants alters floral development to convert flowers into vegetative tissues. We find that phytoplasma produce a novel effector protein (SAP54) that interacts with members of the MADS-domain transcription factor (MTF) family, including key regulators SEPALLATA3 and APETALA1, that occupy central positions in the regulation of floral development. SAP54 mediates degradation of MTFs by interacting with proteins of the RADIATION SENSITIVE23 (RAD23) family, eukaryotic proteins that shuttle substrates to the proteasome. Arabidopsis rad23 mutants do not show conversion of flowers into leaf-like tissues in the presence of SAP54 and during phytoplasma infection, emphasizing the importance of RAD23 to the activity of SAP54. Remarkably, plants with SAP54-induced leaf-like flowers are more attractive for colonization by phytoplasma leafhopper vectors and this colonization preference is dependent on RAD23. An effector that targets and suppresses flowering while simultaneously promoting insect herbivore colonization is unprecedented. Moreover, RAD23 proteins have, to our knowledge, no known roles in flower development, nor plant defence mechanisms against insects. Thus SAP54 generates a short circuit between two key pathways of the host to alter development, resulting in sterile plants, and promotes attractiveness of these plants to leafhopper vectors helping the obligate phytoplasmas reproduce and propagate (zombie plants).