Plasmodium falciparum and plants by screening the entire Malaria Box, a chemical library of novel chemical scaffolds with activity against the blood stage of P. falciparum. Initial screening against Arabidopsis thaliana on agar media and subsequently on soil demonstrated the crucial nature of log P and formal charge are to active molecules. Using this information, a weighted scoring system was applied to a large chemical library of liver-stage effective antimalarial leads, and of the six top-scoring compounds, one had potency comparable to that of commercial herbicides. This novel compound, MMV1206386, has no close structural analogues among commercial herbicides. Physiological profiling suggested that MMV1206386 has a new mode of action and overall demonstrates how weighted rules can help during herbicide discovery programs.Herbicides have physico-chemical properties not unlike orally-delivered human drugs, but are known to diverge in their limits for proton donors, partition coefficients and molecular weight. To further refine rules specific for herbicides, we exploited the close evolutionary relationship between  via a novel mode of action.Trawling hundreds of antimalarials for herbicides, we develop a weighted scoring system for the phys-chem ‘rules’ of herbicide-likeness. Using this, we discover the antimalarial MMV1206386 is herbicidal  Senecio vulgaris, was documented in 1968  was announced by FMC Agricultural Solutions in 2019.4,5 Two old herbicides, cinmethylin and aclonifen, were rediscovered as having new modes of action,6,7 while new compounds with new modes of action have emerged, such as cyclopyrimorate 8 and several novel cyclic methylphosphonates that target the pyruvate dehydrogenase complex.5 The traditional approach to discover herbicides is through mass chemical screening and only later determining the mode of action; as a result this process gives diminishing returns as highly active molecules increasingly match known herbicides or have a known mode of action.The implementation of herbicides in agriculture in the 1940s improved crop productivity, but the emergence of herbicide resistance in the last few decades threatens those gains in yield. The first case of herbicide resistance, triazine-resistant Plasmodium falciparum and plants like Arabidopsis thaliana9,10 means many antimalarial compounds are herbicidal and vice versa e.g. herbicides such as glyphosate, trifluralin, endothall and prodiamine are lethal to Plasmodium species11–14 as antimalarials cycloguanil, pyrimethamine, sulfadoxine, dihydroartemisinin and artesunate are herbicidal.15 The chemical tools for antimalarial drug discovery have burgeoned in the last decade with chemical libraries composed of chemically novel antimalarials made publicly available by large, international consortia.16,17 Exploiting this, two herbicidal compounds were discovered by screening a small subset of compounds from the Malaria Box chemical library against A. thaliana.18,19 Overall, the Malaria Box is a 400-compound set of structurally diverse and chemically simple drug-like molecules that are toxic to blood stage P. falciparum and have physico-chemical properties suitable for orally delivered drugs.17 The screening of this subset against A. thaliana grown on Murashige–Skoog agar medium revealed twenty highly herbicidal compounds.18,19 Ten of these were tested against soil-grown A. thaliana, and only two remained highly herbicidal, despite all ten molecules having physico-chemical properties within the broad range observed for commercial herbicides.18,19 There are lessons to be learned from looking at compounds that succeed as herbicides on plate-based assays, but fail in soil-based assays. Instead of a bias towards successes, considering the physico-chemical properties of compounds that fail to translate to soil-based assays might provide more sophisticated rules for predicting which herbicidal hits will continue to work when sprayed on the leaves of soil-grown plants.The close relationship between the malaria parasite 20–22 including a recent study of 334 commercial herbicides,23 demonstrated that although the physico-chemical properties of herbicides were similar to orally delivered drugs, herbicides possess fewer proton donors, a lower partition coefficient and molecular weight.23,24 To better understand the physico-chemical properties favoured by herbicides, we tested the entire Malaria Box for herbicidal activity of plate-based hits and determined which remained against soil-grown plants. There were correlations between some molecular properties and success in soil tests, which improved predictive ability. We used this newly refined set of rules to rank 631 liver-stage effective antimalarials in silico. Of the six highest-scoring compounds we found MMV1206386, a highly herbicidal tetrahydroquinoline derivative and chemically novel herbicidal compound, for which we obtained structure–activity information and determined that the compound potentially possesses a novel mode of action.Previous analyses,in planta bioavailability of compounds from the Malaria Box library (MMV400) we compared their solubility in water (log S), partition (log P) and distribution (log D) coefficients, molar mass, proportion of aromatic atoms and polar surface area with the corresponding parameters of 360 commercial herbicides  was below that of the herbicides (20–60%)  . The MMV0 to 4.7 . Thus, i18,19 so to create a complete dataset of antimalarials to help correlate physico-chemical properties with herbicidal activity, we screened and compiled data for the remaining 240 compounds  of the MMV400 against Arabidopsis thaliana grown aseptically on an agar medium. Seeds were sown on solid agar medium containing 80 μM of the MMV400 compound (see ESIMMV plates B and C (160 compounds) were screened previouslyd see ESI Fig. 1. A. thaliana pre- and post-emergence on soil with a concentration range from 0 to 400 mg L−1. Oryzalin and glyphosate were used as controls, being typical pre- and post-emergence herbicides respectively. Only 16 of the 39 compounds were active against plants grown on soil  were effective both pre- and post-emergence, with strong growth inhibition at an application rate of 50 mg L−1 . As showmergence . These dversus compounds that were only herbicidal on agar. To better describe their molecular properties we used the set of descriptors that included log P, log D, log S, molecular mass, proportion of aromatic atoms, number of hydrogen bond donors and acceptors, number of rotatable bonds, polar surface area and formal charge. For each parameter we compared an average value for compounds active both on soil and agar plates (n = 16) and compounds which were not active on soil, but were active on agar plates (n = 23) and we used a two-sample t-test to determine statistical significance of any differences  difference in the average values was for log P. The mean log P for soil-active compounds (3.5 ± 1) was lower than for compounds that were inactive on soil (4.2 ± 1) and closer to the mean log P for commercial herbicides (2.9 ± 1.5). This indicated that high log P reduced activity against soil-grown plants for antimalarials that were herbicidal on agar. Herbicide-like values for log S (p = 0.08) and number of hydrogen bond donors (p = 0.09) were important, but just showed a trend (p < 0.1).The only significant (p < 0.05) , that was close to 13.6 points for commercial herbicides (n = 360). Scores for plate active-only antimalarials for herbicide likeness varied from 6.5 to 17, with the average value 11.9 points (n = 23) which is significantly different (p < 0.05) from the average value for herbicides and soil-active antimalarials. This scoring system appears to give values consistent for compounds showing herbicidal activity in more natural, soil-grown conditions.Using this scoring system, we plotted distribution curves for antimalarials active only on plates , black ain silico pre-screening of 631 molecules that were active against liver-stage malaria parasites, which possess low hepatotoxicity and potentially good oral bioavailability.25 Consisting of antimalarial compounds a high proportion should be herbicidal, but this liver-active set were structurally different to the blood stage MMV400 antimalarials. We hoped to demonstrate whether the aforementioned rules could focus attention only on compounds with appropriate physico-chemical properties of soil-active herbicidal compounds. We scored all 631  for herbicide-likeness and tested the top six scoring compounds that were commercially available.To test this weighted scoring system on a different dataset, we performed an A. thaliana at 200 mg L−1 application rate in both pre- and post-emergence application  of quinolone ring was crucial for herbicidal activity: removal of this group in 2 completely eliminated pre-emergence activity and significantly reduced post-emergence activity.To assess the importance of the furanyl motif marked,  we replaIncreasing the heterocyclic nature of the five-membered ring as in 11 and 12 or increasing the functionality of the five membered ring as in 5, 17, 18, 26 also lost activity. Removal of the 3-methyl group as in 19 clearly reduced pre- and post-emergence herbicidal activity. Replacement of furan motif with groups which did not contain heterocyclic core 20–22 similarly decreased herbicidal activity or virtually eliminated as in 23. Changing the position of the link between the furan motif and the carbonyl group greatly reduced herbicidal activity in 24, and completely eliminated it in 25. With these results available, we examined the potential of MMV1206386 to act as a herbicide against more relevant weed species. Eight crop specific weed species in pre- and post-emergence application were assayed .Abutilon theophrasti (velvetleaf) and Setaria viridis (green bristlegrass). Moderate susceptibility was observed in the case of A. retroflexus whereas E. crus-galli was moderately sensitive to pre-emergence treatment (45% of control at 2 kg ha−1), but tolerant to post-emergence treatment. Three species, A. fatua, A. spica-venti and S. faberi were resistant to MMV1206386. Based on these data we can assume that MMV1206386 has the potential to control a wide range of species, and should be more successful if used as a post-emergence herbicide. Since a search of MMV1206386 structural analogues among known commercial herbicides did not find any structurally similar molecules, we thought MMV1206386 might have a novel mode of action. To determine this we obtained an industry-standard physiological profile, which includes 13 different assays and generates a profile that can be compared to commercial herbicides, for many their modes of action being known.19,26,27 Firstly, we tested MMV1206386 against small plants and cell suspension to see which symptoms are induced by treatment with the compound  cell suspension culture at 100 μM. At lower concentrations cell division was only mildly affected. Growth of Lemna paucicostata (duckweed) was strongly inhibited when the compound was applied at 10 μM and 100 μM accompanied by rapid necrosis, reduced leaf growth and root growth inhibition. Treatment of plate-grown A. thaliana by MMV1206386 caused chlorosis, reduced leaf growth, root growth inhibition and hypocotyl swelling in seedlings, and these symptoms were similar to what was observed for soil-grown plants treated with MMV1206386. The germination inhibition assay with dark-grown Lepidum sativum (cress) showed that MMV1206386 had a moderate effect on germination rate. In contrast, when L. sativum plants were grown under light the inhibition of germination was more than 70% at all tested concentrations.MMV1206386 strongly inhibited cell division in heterotrophic Lemna paucicostata was only slightly affected at 100 μM. MMV1206386 demonstrated robust or medium uncoupler activity: the electron transport activity dropped by 46% and 30% at 100 μM and 10 μM respectively upon treatment, as well as ATP levels decreased robustly. Interestingly, there was no effect on the cress very long chain fatty acid synthesis (at 1 μM), carbon dioxide assimilation (at 1000 μM), respiration (at 100 μM) or reactive oxygen species accumulation (at 10 μM and 100 μM). To find out what mode of action MMV1206386 had, this physiological profile was compared with the BASF database of physiological profiles representing all known modes of action for herbicides and reference compounds with standard modes of action. This comparison did not reveal any matches among fingerprint profiles for commercial herbicides, therefore suggested that MMV1206386 represents a novel mode of action.Compared to industry-standard physiological profiles of inhibitors of photosystem II, MMV1206386 mildly inhibited photosynthetic electron transport in photosystem II in isolated wheat thylakoids at 100 μM . In the 20–23,28 Where the underpinning datasets were made known, these consisted of commercial herbicides, so none of these studies considered initial herbicidal hits that then failed in foliar applications.20,22,23 Only the study by Clarke considered data from both successful and unsuccessful herbicidal leads.21 Unfortunately, as the identities of their training set was suppressed, no subsequent analysis could use these data.Since the advent of Lipinski's rules for oral drugs in 1997 several studies have analysed the physico-chemical parameters of herbicides.A. thaliana on agar plates and then tested a sub-set against soil-grown plants. The reason to choose the Malaria Box was the fact that it was partially screened in previous studies and yielded many herbicidal hits, so screening the rest of the library would expand the training set.18,19 Screening the entire MMV400 increased the number of actives tested on soil and agar from 9 to 39 compounds plants, enabling statistical analyses like Fisher's exact test and two sample t-test.To create a dataset containing positive and negative data we completed screening of the 400-compound Malaria Box against 20–22 The original ‘rule of five’ employed a few simple descriptors such as partition coefficient (log P), molecular weight, number of hydrogen bond donors and acceptors and rotatable bond count to predict oral bioavailability of a drug candidate.24 These parameters do not consider ionisation properties, polarity or solubility, so to better characterise the physico-chemical parameters of herbicidal and non-herbicidal molecules we used an extended set of descriptors.23 The set included all Lipinski's descriptors as well as: distribution coefficient (log D); characterises distribution of the dominant ionisation form at given pH, solubility coefficient (log S); characterises solubility of molecules, polar surface area, aromatic atom proportion and formal charge. Not surprisingly, compounds active against soil-grown plants as well as compounds active only against plate-grown plants fit within characteristic limits of physico-chemical properties for commercial herbicides. The log P of antimalarials active against soil-grown plants had a low average value of log P that did not differ significantly from commercial herbicides, whereas the antimalarials active only against agar-grown plants had significantly higher log P value.To describe molecular properties of herbicides, previous studies used Lipinski's ‘rule of five’ itself or with minor corrections.29,30 it might impede translocation of herbicide molecules. This is similar to what has been observed for nanoparticles31 and fertilizers,32 where in contrast negatively charged and neutral particles have increased translocation.33 In addition, organic soils are in general possess negatively charged materials and so positively charged herbicides are readily bound, limiting pre-emergent efficacy.34Another parameter that differed was formal charge. Soil-active antimalarials were mostly neutral or negatively charged. Although positive charge facilitates absorption by roots or leaves,in silico screening of libraries and find new herbicides. The only published scoring system for herbicide-likeness was one proposed by Avram et al. in 2014  for the symptoms observed in Lemna paucicostata treated by MMV1206386, however the physiological profiles did not match those obtained for MMV1206386. The combination of structural uniqueness, distinct physiological profiles and unique combination of symptoms support the hypothesis that MMV1206386 has a new mode of action.For the library targeted against liver-stage 23 and as a prelude to this study, we updated this database. Dimethylarsinic acid, DSMA (disodium methyl arsenate) and MSMA (monosodium methyl arsenate) were removed as they are rarely or no longer used due to toxicity.36 Acrolein, which is used as a commercial algicide, was removed because the database is focused on herbicides applied against soil-grown weeds. Metolachlor, a racemic mixture of S-metolachlor and R-metolachlor, was excluded because it duplicated physico-chemical properties of S-metolachlor that are already present in the database. To check if we missed any herbicides in the first iteration we screened through “Alan Wood's Pesticides Common Names Compendium” and “Pesticide Properties Data Base by the University of Hertfordshire” and found 27 commercial herbicides not in the original database.36,37 These include four 4-hydroxyphenylpyruvate dioxygenase inhibitors ; five that affect protoporphyrinogen oxidase ; three photosystem II inhibitors ; two synthetic auxins ; and six herbicides from different groups, including the acetyl-CoA carboxylase inhibitor haloxyfop-P, the acetolactate synthase inhibitor monosulfuron, 1-deoxy-d-xylulose 5-phosphate synthase inhibitor bixlozone, a phytoene desaturase inhibitor metflurazon, an auxin transport inhibitor thidiazuron, and an inhibitor of long chain fatty acid synthesis terbuchlor. Seven of the newly added herbicides have unknown modes of action . In addition, a few herbicides have been introduced to market since 2015 and so were also added. These three herbicides each possess a novel mode of action: an inhibitor of pyruvate dehydrogenase (clacyfos), an inhibitor of homogentisate solanesyltransferase (cyclopyrimorate) and an inhibitor of dihydroorotate dehydrogenase (tetflupyrolimet). The SMILES codes of the newly added compounds were used to propagate their details and the new database , partition coefficient (log P), distribution (log D) coefficient, molar mass, proportion of aromatic atoms, polar surface area, rotatable bond count, hydrogen bond donor count, hydrogen bond acceptor count and formal charge. The parameter values were calculated using calculator plugins included in Marvin Suite program package v. 20.19 (ChemAxon). Formal charge, hydrogen bond donor count, hydrogen bond acceptor count, were calculated for the major tautomeric form at pH 7.4.To describe physico-chemical properties of the Malaria Box compounds a set of physico-chemical descriptors was generated. These included solubility coefficient  was placed into a well of a sterile transparent 96-well plate prior to pouring of 250 μL of molten MS-agar medium that contained 1% of agar, 4 g L−1 of Murashige–Skoog, 10 g L−1 of glucose and 0.3% 2-(N-morpholino) ethanesulfonic acid (v/v), pH 5.7. After the agar solidified roughly 30–40 ethanol-sterilised A. thaliana (Col-0) seeds were sown onto the surface as 25 μL of seed suspension in 0.1% agar. Prior to the experiment the seeds were stratified for three days to synchronise germination. After the surface of agar dried the plates were covered with lids and sealed with porous tape, transferred to a growth chamber and left to grow under long-day illumination  at 26 °C and 60% relative humidity. After sixteen days, lids were removed and images taken.To assess herbicidal activity of the Malaria Box compounds they were tested against agar-grown A. thaliana Col-0 seeds were sown in 63 × 63 × 59 mm pots consisting of Irish peat pre-wet before sowing. Seeds were treated for 3 days in the dark at 4 °C to synchronise germination and then grown in a chamber at 22 °C, with 60% relative humidity and in a 16 h light/8 h dark photoperiod. Antimalarial compounds and control herbicide oryzalin were initially dissolved in DMSO at 20 mg mL−1 and further diluted in water containing 0.02% surfactant  prior to treatments. Another herbicide control, glyphosate was diluted in the same manner, but the original 20 mg mL−1 stock was prepared in water. DMSO at a concentration of 2% (v/v) was used as a negative control. Seeds or seedlings were treated as previously detailed19 with 500 μL of 0, 25, 50, 100, 200 or 400 mg L−1 solutions of each compound. Pre-emergence treatments were done as trays were moved into their first long day, whereas post-emergence treatments were conducted three and six days after germination. Seedlings were grown for 16 days after treatment before photos were taken.To assess herbicidal activity ∼30 26,27 The influence of MMV1206386 on cell growth was studied in cell suspensions of phototrophic green algae Scenedesmus obliquus. The effect of MMV1206386 on Hill reaction rate was assessed in isolated wheat (Triticum aestivum) chloroplasts. Carbon assimilation and oxygen consumption was studied in heterotrophic Galium mollugo cell suspensions. Oxidative phosphorylation uncoupler activity, ATP content, chlorophyll fluorescence and accumulation of reactive oxygen species were measured in Lemna paucicostata. Toluidine-blue staining of Lepidium sativum hypocotyls was used for the detection of inhibition of very long chain fatty acid synthesis. Additionally the effect of MMV1206386 on A. thaliana seedling morphology was evaluated.To determine the mode of action of MMV1206386 the effect of the compound on different physiological processes was studied according to protocols previously described.By comparing failed and successful hits from the Malaria Box it was revealed how different molecular properties had different impacts on the chance of herbicidal activity. Having a suitable partition coefficient and formal charge appeared essential, whereas other parameters could range more widely. Based on these findings we developed a weighted scoring system for herbicide-likeness and used it to select top-scoring compounds from a large compound library of liver-stage effective antimalarial leads. One molecule (MMV1206386) had efficiency against soil-grown plants comparable to commercial herbicides and no close structural analogues in use and its physiological profile indicate a new mode of action. Thus, the weighted rules is a useful tool when using high throughput screening approaches in the discovery of new herbicides.There are no conflicts to 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Dear editor,® mouthwash for reducing COVID-19 infection and progression [®, an antiviral phthalocyanine derivative (APD), in a gargle/rinse mouthwash protocol [® was indicated against SARS-CoV-2 , Brazil (Finance Code 001).Bernardo da Fonseca Orcina:https://orcid.org/0000-0003-3367-483XVerônica Caroline Brito Reia:https://orcid.org/0000-0003-1352-5474Andrea Name Colado Simão:https://orcid.org/0000-0002-2073-6782Audrey Alesandra Stinghen Garcia Lonni: https://orcid.org/0000-0001-6498-2806Thais Maria Freire Fernandes:https://orcid.org/ 0000-0002-4368-8568Marcelo Lupion Poleti:https://orcid.org/0000-0003-1904-5762Fabiano Vieira Vilhena:https://orcid.org/0000-0003-3840-3633Paulo Sérgio da Silva Santos:https://orcid.org/0000-0002-0674-3759


Revista da Sociedade Brasileira de Medicina Tropical/Journal of the Brazilian Society of Tropical MedicineTitle: Spondylodiscitis complicated by paraspinal abscess in a 10-year-old child 54: (e0134-2021) 2021 - Page: 1 - doi: 10.1590/0037-8682-0134-2021 Correct indexing of authors:Maio, Nicoletta diSessa, Anna DiShould read:Di Maio, NicolettaDi Sessa, Anna


Utilizating the plant microbiome to enhance pathogen resistance in crop production is an emerging alternative to the use of chemical pesticides. However, the diversity and structure of the microbiota, and the assembly mechanisms of root-associated microbial communities of plants are still poorly understood.Magnaporthe oryzae (M. oryzae) isolate KJ201, using 16S rRNA and internal transcribed spacer 1 (ITS1) amplicon sequencing. The rhizosphere soils showed higher bacterial and fungal richness and diversity than the endosphere except for fungal richness in the rhizosphere soils of the mock treatment. Bacteria richness and diversity increased in the endospheric communities of NPB and Piz-t under inoculation with KJ201  compared with the corresponding mock treatments, with the NPB-KJ201 showing the highest diversity in the four bacterial endocompartments. In contrast, fungal richness and diversity decreased in the endospheric communities of NPB-KJ201 and Piz-t-KJ201, relative to the corresponding mock treatments, with NPB-KJ201 and Piz-t-KJ201 having the lowest richness and diversity, respectively, across the four fungal endocompartments. Principal component analysis (PCA) indicated that the microbiota of Piz-t-KJ201 of root endophytes were mostly remarkablely distinct from that of NPB-KJ201. Co-occurrence network analysis revealed that the phyla Proteobacteria and Ascomycota were the key contributors to the bacterial and fungal communities, respectively. Furthermore, a comparative metabolic analysis showed that the contents of tryptophan metabolism and indole alkaloid biosynthesis were significantly lower in the Piz-t-KJ201 plants.We invstigated the microbiota of the root endosphere and rhizosphere soils of the rice cultivar Nipponbare (NPB) and its Piz-t-transgenic line (NPB-Piz-t) when infected with the filamentous fungus M. oryzae played dominant roles in determining the microbial community assemblage. Further metabolomics analysis revealed that some metabolites may influence changes in bacterial communities. This study improves our understanding of the complex interactions between rice and M. oryzae, which could be useful in developing new strategies to improve rice resistance through the manipulation of soil microorganisms.In this study, we compared the diversity, composition, and assembly of microbial communities associated with the rhizosphere soils and endosphere of Piz-t-KJ201 and NPB-KJ201. On the basis of the different compositions, diversities, and assemblies of the microbial communities among different compartments, we propose that the host genotype and inoculation pattern of The online version contains supplementary material available at 10.1186/s12284-021-00486-9. Plant pathogens are an ever-increasing threat to crop production; hence, there is an urgent need to suppress disease under natural plant conditions. To achieve this, the root-associated microbiome, has been suggested as a disease-control alternative owing to its antagonistic abilities, which have been described for various soil-borne pathogens, including fungi, bacteria, oomycetes, and nematodes , a global hemibiotrophic plant fungal pathogen, causes serious blast disease at any time during rice production  generation or transcriptional reprogramming processes, and even affecting the level of the root microbiome  was employed to identify fungal community biomarkers based on the 8 compartments of data. Seven significantly different groups of fungi were enriched in the endospheric communities of Piz-t-KJ201, including one Fungi_sp., one Schizothecium and 5 unidentified fungi (from phylum to family) were primarily enriched by healthy plants, such as the endospheric communities of NBP-mock and the rhizosphere soils of Piz-t-KJ201, while in the diseased NPB-KJ201, the endospheric bacteria were mainly enriched by the bacterial lineages of Chloroflexi . Additional KEGG enrichment analysis showed that metabolic pathways, biosynthesis of secondary metabolism, glycerophospholipid metabolism, glycerolipid metabolism, and tryptophan metabolism were the most significant pathways in NPB-KJ201 compared with mock treatments , the causal agent of rice blast  metabolism acts as a common hub for the biosynthesis of many immune-related compounds . The rice cultivars NPB and NPB-Piz-t were used in this experiment, and NPB-Pizt was generated as described in our previous study  according to the manufacturer’s instructions. The DNA quality and concentration were monitored using a NanoDrop 1000 spectrophotometer . The total DNA was used as PCR templates, and 16S amplicon libraries were generated using the PCR primers 319F (5′-CCTACGGGNGGCWGCAG-3′) and 806R (5′-GGACTACHVGGGTWTCTAA T-3′) with an adapter (index) that targets the V3 and V4 variable regions of bacterial/archaeal 16S rRNA genes  and ITS1R (5′-GCTGC GTTCTTCATCGATGC-3′)  and filtered  for UPLC-MS/MS analysis.The freeze-dried above ground parts were crushed using a mixer mill  with zirconia beads for 1.5 min at 30 Hz. A total of 100 mg powder was weighed and extracted overnight at 4 °C with 0.6 ml 70% aqueous methanol. Following centrifugation at 10,000 g for 10 min, the extracts were absorbed , and the annotated metabolites were then mapped to the KEGG Pathway database (http://www.kegg.jp/ kegg/pathway.html).The hierarchical cluster analysis (HCA) results of samples and metabolites were presented as heatmaps with dendrograms. HCA was conducted using an R package p heatmap (Qin et al. Additional file 1: Fig. S1. ANOSIM analysis was performed based on a Bray-Curtis distance matrix from each compartment to calculate the differences between rhizosphere soils and endosphere compartments. Permutation test, number of permutation is 999. Bacterial communities, A:NPB-Mock-B.R, B: Pizt-Mock-B.R, C: NPB-KJ201-B.R, D: Piz-t-KJ201-B.R, E:NPB-Mock-B.E, F: Pizt-Mock-B.E, G: NPB-KJ201-B.E, H: Piz-t-KJ201-B.E; Fungal communities, A:NPB-Mock-F.R, B: Pizt-Mock-F.R, C: NPB-KJ201-F.R, D: Piz-t-KJ201-F.R, E:NPB-Mock-F.E, F: Pizt-Mock-F.E, G: NPB-KJ201-F.E, H: Piz-t-KJ201-F.E.Additional file 2: Fig. S2. Venn map of bacterial and fungal communities in the rhizospheres soils and endosphere of NPB-KJ201 and Piz-t-KJ201 plants. Bacterial communities, A:NPB-Mock-B.R, B: Pizt-Mock-B.R, C: NPB-KJ201-B.R, D: Piz-t-KJ201-B.R, E:NPB-Mock-B.E, F: Pizt-Mock-B.E, G: NPB-KJ201-B.E, H: Piz-t-KJ201-B.E; Fungal communities, A:NPB-Mock-F.R, B: Pizt-Mock-F.R, C: NPB-KJ201-F.R, D: Piz-t-KJ201-F.R, E:NPB-Mock-F.E, F: Pizt-Mock-F.E, G: NPB-KJ201-F.E, H: Piz-t-KJ201-F.E.Additional file 3: Fig. S3. Indicator fungal groups across 8 compartments with LDA values higher than 3.LDA: linear discriminant analysis. A:NPB-Mock-F.R, B: Pizt-Mock-F.R, C: NPB-KJ201-F.R, D: Piz-t-KJ201-F.R; E:NPB-Mock-F.E, F: Pizt-Mock-F.E, G: NPB-KJ201-F.E, H: Piz-t-KJ201-F.E.Additional file 4: Fig. S4. Indicator bacterial groups across 8 compartments with LDA values higher than 3. LDA: linear discriminant analysis. A:NPB-Mock-B.R, B: Pizt-Mock-B.R, C: NPB-KJ201-B.R, D: Piz-t-KJ201-B.R; E:NPB-Mock-B.E, F: Pizt-Mock-B.E, G: NPB-KJ201-B.E, H: Piz-t-KJ201-B.E.Additional file 5: Table S1. OTUs for bacterial and fungal communities.Additional file 6: Table S2. Topphylum for bacterial and fungal taxa across 8 compartments.Additional file 7: Table S3. Statistical table of alpha diversity index for bacterial and fungal communities.Additional file 8: Table S4. PCA for bacterial and fungal compartments.Additional file 9: Table 5. The significance difference metabolism of Piz-t-KJ201 and NPB-KJ201.Additional file 10: Table S6. The statistic analysis of KEGG enrichment for each group.