Bacterial Compounds Research Articles

BIOLOGICAL AND DOCKING STUDIES OF NOVEL AROYLHYDRAZONES

Objective: Novel aroylhydrazone schiff bases were synthesized and were screened for their biological activities.Methods: Using HCl as a catalyst, all the compounds were synthesized at room temperature and were characterized by IR and NMR techniques. The synthesized Schiff bases were screened for antibacterial, antifungal activities. In silico molecular docking, method was performed to study their anti-tuberculosis activity against enoyl acyl carrier protein reductase (InhA) from Mycobacterium tuberculosis (PDB id: 2NSD). Results: Compound P1 showed good antibacterial activity against gram positive (S. aureus) and gram negative (E. coli) bacterial strains and compound J1 showed good antifungal activity against A. niger. Molecular docking results reveal that compound B1 made two numbers of electrostatic interactions with 2NSD with more negative C docker interaction value. This indicated that the compound B1 was more active with minimum binding potential which is comparable with that of standard compound isoniazid.Conclusion: Aroylhydrazones having good biologically activities compared to that of standards were prepared.

New bioactive compounds from the marine-derived actinomycete Nocardiopsis lucentensis sp. ASMR2

Abstract In the search for new bioactive compounds from extremophilic actinomycetes, a new marine actinomycete strain, Nocardiopsis lucentensis sp. ASMR2 has been isolated and taxonomically identified from marine plants collected in the Red Sea at Hurghada coasts. A large-scale fermentation of the strain on modified rice solid medium was performed, followed by work-up and purification of the obtained extract using a series of chromatographic purifications, delivering the novel butenolide system 3′-hydroxy-N-(2-oxo-2,5-dihydrofuran-4-yl)propionamide (1a) along with the naturally new 4-methoxy-2H-isoquinolin-1-one (2). Furthermore, eight known bioactive compounds are also reported, namely, indole-3-carboxylic acid, indole-3-acetic acid, indole-3-acetic acid methyl ester, furan-2,5-dimethanol, tyrosol, glycerol linoleate, cyclo-(Tyr, Pro), and adenosine. The chemical structures of the new compounds (1a, 2) were confirmed by extensive one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) spectroscopy, electron ionization high resolution (EI-HR) mass spectrometry, and by comparison with literature data. The antimicrobial activity of the strain extract, as well as of compounds 1a and 2, were studied using a panel of pathogenic microorganisms. The in vitro cytotoxicity of the bacterial extract and compounds 1a and 2 were studied against the human cervix carcinoma cell line (KB-3-1) and its multidrug-resistant subclone (KB-V1).

Bacillus methylotrophicus M4-96 isolated from maize (Zea mays) rhizoplane increases growth and auxin content in Arabidopsis thaliana via emission of volatiles

Plant growth-promoting rhizobacteria stimulate plant growth and development via different mechanisms. In this study, we characterized the effect of volatiles from Bacillus methylotrophicus M4-96 isolated from the maize rhizosphere on root and shoot development, and auxin homeostasis in Arabidopsis thaliana. Phytostimulation occurred after 4days of interaction between M4-96 and Arabidopsis grown on opposite sides of divided Petri plates, as revealed by enhanced primary root growth, root branching, leaf formation, and shoot biomass accumulation. Analysis of indole-3-acetic acid content revealed two- and threefold higher accumulation in the shoot and root of bacterized seedlings, respectively, compared to uninoculated plants, which was correlated with increased expression of the auxin response marker DR5::GUS. The auxin transport inhibitor 1-naphthylphthalamic acid inhibited primary root growth and lateral root formation in axenically grown seedlings and antagonized the plant growth-promoting effects of M4-96. Analysis of bacterial volatile compounds revealed the presence of four classes of compounds, including ten ketones, eight alcohols, one aldehyde, and two hydrocarbons. However, the abundance of ketones and alcohols represented 88.73 and 8.05%, respectively, of all airborne signals detected, with acetoin being the main compound produced. Application of acetoin had a different effect from application of volatiles, suggesting that either the entire pool or acetoin acting in concert with another unidentified compound underlies the strong phytostimulatory response. Taken together, our results show that B. methylotrophicus M4-96 generates bioactive volatiles that increase the active auxin pool of plants, stimulate the growth and formation of new organs, and reprogram root morphogenesis.

Microbiota and metabolome during controlled and spontaneous fermentation of Nocellara Etnea table olives

This study is aimed to investigate bacterial community and its dynamics during the fermentation of Nocellara Etnea table olives and to study its effect on metabolome formation. Six different combination of bacterial cultures (BC1-BC6) were used as starters for table olive fermentation and one additional process, conducted without addition of any starters, was used as control (C). The processes were conducted in triplicate and, overall, 21 vessels were performed at industrial scale. The fermentation was monitored for 120 days through culture-dependent and –independent approaches. Microbial counts of the main microbial groups revealed slight differences among brine samples, with the exception of LAB counts and Enterobacteriaceae, which were higher and lower, respectively, in most of the inoculated samples than the control ones. In addition, results demonstrated that the use of bacterial cultures (except the BC1), singly or in different combinations, clearly influenced the fermentation process reducing the final pH value below 4.50. When microbiota was investigated through sequencing analysis, data revealed the presence of halophilic bacteria and, among lactobacilli, the dominance of Lactobacillus plantarum group at the initial stage of fermentation, in all brine samples, except in the BC5 in which dominated Lactobacillus casei group. At 60 and 120 days of fermentation, an overturned bacterial ecology and an increase of biodiversity was observed in all samples, with the occurrence of Lactobacillus paracollinoides, Lactobacillus acidipiscis and Pediococcus parvulus. Correlation between bacterial OTU and volatile organic compounds (VOCs) revealed that, aldehydes and alcohol compounds exhibited a positive correlation with Proteobacteria, while several esters with LAB and Hafnia. In particular, esters, associated with fruity and floral notes, were positively correlated to L. paracollinoides, L. acidipiscis, and P. parvulus species. Although the VOCs amounts were sample-specific, overall aldehydes were mostly produced at the beginning of the fermentation, while acids, alcohols and esters at the end of the process.

The association of bacterial C9-based TTX-like compounds with Prorocentrum minimum opens new uncertainties about shellfish seafood safety

In 2012, Tetrodotoxin (TTX) was identified in mussels and linked to the presence of Prorocentrum minimum (P. minimum) in Greece. The connexion between TTX and P. minimum was further studied in this paper. First, the presence of TTX-producer bacteria, Vibrio and Pseudomonas spp, was confirmed in Greek mussels. In addition these samples showed high activity as inhibitors of sodium currents (INa). P. minimum was before associated with neurotoxic symptoms, however, the nature and structure of toxins produced by this dinoflagellate remains unknown. Three P. minimum strains, ccmp1529, ccmp2811 and ccmp2956, growing in different conditions of temperature, salinity and light were used to study the production of toxic compounds. Electrophysiological assays showed no effect of ccmp2811 strain on INa, while ccmp1529 and ccmp2956 strains were able to significantly reduce INa in the same way as TTX. In these samples two new compounds, m/z 265 and m/z 308, were identified and characterized by liquid chromatography tandem high-resolution mass spectrometry. Besides, two TTX-related bacteria, Roseobacter and Vibrio sp, were observed. These results show for the first time that P. minimum produce TTX-like compounds with a similar ion pattern and C9-base to TTX analogues and with the same effect on INa.

Relationship of consequences of anastomotic insufficiency and bacterial flora of oral cavity in patients with esophageal and cardia cancer

In the course of anastomotic insufficiency following resection of esophageal cancers the bacterial compound of the esophageal substance has a remarkable, presumable role in the outcome of complications. The purpose of this study is to compare the consequences of the anastomotic leak with the bacterial flora of patients' oral cavity. In this prospective study a total of 131 patients were investigated directly before the surgical intervention taking a bacterial sample. Bacterial flora of patients' oral cavity was analysed; and the correlation between the consequences of the anastomotic leak and the content of the bacterial flora was examined. Pathogenic bacteria in the oral microflora in 50 cases (38.2%) was found. Statistically significant, moderate correlation was found between the severity of the complication and the incidence of pathogenic bacteria (rs = 0.553; p≤0.05). Pathogenic agent in the microbial flora might induce higher risk and more severe outcome in case of anastomotic leakage and it might be evaluated as a determinative factor. Consideration of the bacterial flora of the oral cavity requires more attention in the preoperative preparation than before and it demands the change of the current practice. Orv. Hetil., 2017, 158(1), 25-30.

Molecular basis of quorum sensing signal-response systems in bacteria

Bacteria use quorum sensing (QS) to conduct gene expression programmes connected with collective behaviors. QS indicates on the capacity of bacteria to monitor their population density and regulate gene expression. QS activates from tens to hundreds of genes that underlie different biological processes. The QS-regulated processes organize horizontal gene transfer, the formation of biofilms, multicellular behaviors, microbe–host and microbe–microbe relations. The QS signaling requires the production, release, detection, exchange and perception of bacterial compounds, known as autoinducers or QS signals. Recently, new autoinducers have been discovered in bacteria and it has been shown how these molecules are recognized by the respective receptors. Autoinducers belong to three major classes: acyl-homoserine lactones (AHLs) used by Gram-negative bacteria, specific oligopeptides used by Gram-positive bacteria and universal autoinducers. The aim of this paper is to provide an overview of molecular basis of the QS phenomenon, characterization of intra- and interspecies QS signaling molecules and biological processes regulated by these molecules.

A novel small molecule immunoassay to detect the mycobacterial siderophore carboxymycobactin

Background: To diagnose tuberculosis (TB), it is necessary to demonstrate the presence of Mycobacterium tuberculosis in a clinical specimen such as sputum. A simple, low-cost rapid test for blood or urine is urgently needed but remains elusive. Tests for host response-derived biomarkers or secreted bacterial compounds have so far failed to provide sufficient sensitivity or specificity and alternative approaches are needed. Carboxymycobactins are amphiphilic siderophores unique to the mycobacteria that have the ability to transverse mammalian cell walls. They have insufficient mass to induce an antibody response and there are currently no simple sensitive tests for their detection. Methods: We report the development of an enzyme-linked immunosorbent assay (ELISA) for carboxymycobactin. Polyclonal antibodies were raised in rabbits following conjugation to a carrier protein, bovine serum albumin allowing development of a sensitive indirect double antibody ELISA. A second keyhole limpet hemocyanin conjugate was manufactured to adhere the hapten to the wells of the microplate. We established a limit of detection for the assay of 1 pg/ml. Carboxymycobactin was detected in culture supernatant from mycobacteria including clinical isolates of M. tuberculosis , but not from cultures of Rhodococcus, Nocardia, Streptomyces, Bacillus cereus, Klebsiella oxytoca, Staphylococcus aureus, Escherichia coli , and Pseudomonas aeruginosa . Sample concentration was achieved following extraction with chloroform. Results: We have demonstrated for the first time the direct detection of carboxymycobactin in culture supernatant by immunoassay. Conclusions: We recommend testing samples from humans and animals to establish the potential utility of carboxymycobactin as a diagnostic marker of active mycobacterial disease.

Chemical study on Paenibacillus odorifer, a bacterial species isolated from lichen

Recent studies have admitted that bacterial communities were an important united partner of mini-ecosystem lichen symbiosis. Lichen, moreover, is also a rich source of new bacterial lineages and novel bacterial compounds. Therefore, microorganism communities isolated from lichens became a significant subject as a great potential of natural product discovery. Paenibacillus odorifer, a bacterium belonging to Firmicutes, was isolated from Rhizocarpon geographicum, a particular popular crust-forming rock lichen. Assessing its optimal growth conditions was conducted to improve its metabolite production yield by measure of optical density (OD) and by analysis of its chemical profile via TLC, HPLC, LC-MS. Firstly, the parameters chosen for optimal culture were kind of medium, pH and temperature. Results revealed that the growth of P. odorifer was better at 250C using Gym Streptomyces liquid medium supplemented with CaCO3 at pH=7. Secondly, the fermentation was launched by applying the best conditions of bacterial growth. After the 3-day culture using a bioreactor, the supernatant and bacterial cells were separated by centrifugation and organic compounds were absorbed from supernatant by XAD-7 resin. The desorption from resin was carried out through several stages to collect raw extract. TLC, HPLC and LC-MS analyses highlighted that this extract was a rich source of metabolites. Then, the crude extract was fractionated via flash chromatography on a 40 g C18 reversed-phase column, using a gradient solvent system of CH3CN-H2O at 15 mL/min flow rate in 75 min. Two diketopiperazines were isolated from the fractions by applying semi-preparative HPLC (Prevail C18 column, various ratios of CH3CN) such as cyclo(L-Phe-L-Val) and cyclo(L-Phe-L-Ile). Correspondingly, fermentation of P. odorifer could produce valuable compounds for future research.

Nonalcoholic steatohepatitis and the intestinal microbiota

Nonalcoholic steatohepatitis and the intestinal microbiota

Inhibition of Lipopolysaccharide-Induced Interleukin 8 in Human Adenocarcinoma Cell Line HT-29 by Spore Probiotics: B. coagulans and B. subtilis (natto).

Probiotics are used as a treatment for different intestinal disorders. They confer health benefits by different ways. This study was aimed to investigate immunomodulatory effect of Bacillus probiotic spores on the production of lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) in HT-29 intestinal epithelial cells. Differentiated intestinal epithelial cell line was used as a model for the study of colonization of purified spores (Bacillus subtilis (natto) and B. coagulans) and their anti-inflammatory effects. MTT assay and trypan blue staining were used for the detection of optimal concentration of the purified spores and LPS. Pre-treatment assay was done by treatment of the cells with the purified spores for 2h, followed by challenges with LPS for 3 and 18h. Post-treatment assay was done by initial treatment of the cells with LPS for 18h, followed by the spores for 3 and 6h. Levels of IL-8 secretion and its mRNA expression were measured by ELISA and relative Q real-time PCR. Our results showed similar rates of adherence to intestinal epithelial cells by the spore probiotics, while displaying no cytotoxic effect. In the pre-treatment assay, a significant decrease in IL-8, at both protein and mRNA levels, was measured for B. coagulans spores after the addition of LPS, which was higher than those observed for Bacillus subtilis (natto) spores. In the post-treatment assay, while Bacillus subtilis (but not B. coagulans) diminished the LPS-stimulated IL-8 levels after 3h of incubation, the inhibitory effect was not constant. In conclusion, ability of Bacillus spore probiotics for adherence to intestinal epithelial cell and their anti-inflammatory effects, through interference with LPS/IL-8 signaling, was shown in this study. Further studies are needed to characterize responsible bacterial compounds associated with these effects.

Effect of Lactobacillus paracasei Culture Filtrates and Artichoke Polyphenols on Cytokine Production by Dendritic Cells.

The most recent trend in research on probiotic bacteria aims at the exploitation of bioactive bacterial compounds that are responsible for health-promoting effects and suitable for medical applications. Therefore, the main purpose of this study was to ascertain if the immunomodulatory effects of L. paracasei strains on dendritic cells (DCs) were caused by bacterial metabolites released in the culture medium. For that reason, bacterial strains were grown in two media generally used for the culture of DCs, and the effects of culture filtrates on the maturation of DCs and cytokine production were evaluated. Moreover, to reveal potential synergistic effects on the immunomodulation of DCs, an artichoke phenolic extract (APE) was added to the media before bacterial growth. The experiments pointed out an interesting anti-inflammatory activity of a culture filtrate obtained after growing a probiotic L. paracasei strain in one of the media supplemented with APE. Therefore, this culture filtrate—which combines the anti-inflammatory activity and the other well-known health-promoting properties of artichoke phenolic compounds—could represent the basis for future particular exploitations.

GM-CSF Down-Regulates TLR Expression via the Transcription Factor PU.1 in Human Monocytes.

Toll-like receptors (TLR) are crucial sensors of microbial agents such as bacterial or viral compounds. These receptors constitute key players in the induction of inflammation, e.g. in septic or chronic inflammatory diseases. Colony-stimulating factors (CSFs) such as granulocyte-macrophage-CSF (GM-CSF) or granulocyte-CSF (G-CSF) have been extensively investigated in their capacity to promote myelopoiesis in febrile neutropenia or to overcome immunosuppression in patients suffering from sepsis-associated neutropenia or from monocytic immunoincompetence. We report here that GM-CSF, downregulates TLR1, TLR2 and TLR4 in a time- and dose-dependent fashion in human monocytes. Diminished pathogen recognition receptor expression was accompanied by reduced downstream p38 and extracellular-signal-regulated kinase (ERK) signaling upon lipoteichoic acid (LTA) and lipopolysaccharide (LPS) binding—and accordingly led to impaired proinflammatory cytokine production. Knockdown experiments of the transcription factors PU.1 and VentX showed that GM-CSF driven effects on TLR regulation is entirely PU.1 but not VentX dependent. We further analysed monocyte TLR and CD14 expression upon exposure to the IMID® immunomodulatory drug Pomalidomide (CC-4047), a Thalidomide analogue known to downregulate PU.1. Indeed, Pomalidomide in part reversed the GM-CSF-mediated effects. Our data indicate a critical role of PU.1 in the regulation of TLR1, 2, 4 and of CD14, thus targeting PU.1 ultimately results in TLR modulation. The PU.1 mediated immunomodulatory properties of GM-CSF should be taken into consideration upon usage of GM-CSF in inflammatory or infection-related conditions.

Immunological properties of the bacterial origin compounds

It is shown that microorganisms are an integral element of the mаcroorganism immune system.Peptidoglycan, muramyldypeptyd, teichoic acids are structural components of cell walls of microorganisms. These componentsare an object for recognition of the innate immunity system. The necessity of the bacteria cell walls destruction with a view toobtain the immunotropic products for enteral consumption, able to overcome the intestinal barrier, was substantiated.The use of lactic acid bacteria (ICD) for such purposes is perspective and safe, since the considerable experience oftheir cultivation was accumulated, in addition, ICD have got «GRAS» (Generally Recognized As Safe) status. Waste productsof ICD are organic acids, hydrogen peroxide, bacteriocins and others. These substances have got antagonist activity, implicitlyaffect on the immune system, reducing the antigenic load caused by pathogenic microorganisms.A number of physical, chemical and biochemical methods of bacteria cell walls destruction were considered. Thepriority methods is the soft influence, namely the use of specific enzymes or hydrolases, own autolyzins with a combination ofphysical destruction methods.

Proteomic Studies on the Effects of Lipo-Chitooligosaccharide and Thuricin 17 under Unstressed and Salt Stressed Conditions in Arabidopsis thaliana.

Plants, being sessile organisms, are exposed to widely varying environmental conditions throughout their life cycle. Compatible plant-microbe interactions favor plant growth and development, and help plants deal with these environmental challenges. Microorganisms produce a diverse range of elicitor molecules to establish symbiotic relationships with the plants they associate with, in a given ecological niche. Lipo-chitooligosaccharide (LCO) and Thuricin 17 (Th17) are two such compounds shown to positively influence plant growth of both legumes and non-legumes. Arabidopsis thaliana responded positively to treatment with the bacterial signal compounds LCO and Th17 in the presence of salt stress (up to 250 mM NaCl). Shotgun proteomics of unstressed and 250 mM NaCl stressed A. thaliana rosettes (7 days post stress) in combination with the LCO and Th17 revealed many known, putative, hypothetical, and unknown proteins. Overall, carbon and energy metabolic pathways were affected under both unstressed and salt stressed conditions when treated with these signals. PEP carboxylase, Rubisco-oxygenase large subunit, pyruvate kinase, and proteins of photosystems I and II were some of the noteworthy proteins enhanced by the signals, along with other stress related proteins. These findings suggest that the proteome of A. thaliana rosettes is altered by the bacterial signals tested, and more so under salt stress, thereby imparting a positive effect on plant growth under high salt stress. The roles of the identified proteins are discussed here in relation to salt stress adaptation, which, when translated to field grown crops can be a crucial component and of significant importance in agriculture and global food production. The mass spectrometry proteomics data have been deposited to the ProteomeXchange with identifier PXD004742.

Synthesis of Surface-Modified Iron Oxides for the Solvent-Free Recovery of Bacterial Bioactive Compound Prodigiosin and Its Algicidal Activity.

Prodigiosin (PG) is a bioactive compound produced by several bacterial species. Currently, many technologies are being developed for the production of PG by fermentation processes. However, new challenges are being faced with regard to the production of PG in terms of the recovery and purification steps, owing to the labile nature of PG molecules and the cost of the purification steps. Conventional methods have limitations due to high cost, low reusability, and health hazards. Hence, the present investigation was focused on the development of surface-functionalized magnetic iron oxide ([Fe3O4]F) for solvent-free extraction of bioactive PG from the bacterial fermented medium. Fe3O4 was functionalized with diethanolamine and characterized by FT-IR, diffuse reflectance spectroscopy, thermogravimetric analysis, scanning electron microscopy, and confocal microscopy. The various process parameters, such as contact time, temperature, pH, and mass of Fe3O4, were optimized for the extraction of PG using functionalized Fe3O4. Instrumental analyses confirmed that the PG molecules were cross-linked with functional groups on [Fe3O4]F through van der Waals forces of attraction. PG extracted through Fe3O4 or [Fe3O4]F was separated from the fermentation medium by applying an external electromagnetic field and regenerated for successive reuse cycles. The purity of the extracted PG was characterized by high-performance liquid chromatography, FT-IR, and UV-visible spectroscopy. The iron oxide-diethanolamine-PG cross-linked ([Fe3O4]F-PG) composite matrix effectively deactivates harmful fouling by cyanobacterial growth in water-treatment plants. The present investigation provides the possibility of solvent-free extraction of bacterial bioactive PG from a fermented medium using functionalized magnetic iron oxide.

Synthesis of 2-, 3- or 4-phenylsubtituted Chalcones Based on 4- phenylamino-6-nitro-2-[(E)-2-phenylvinyl]quinoline, Evaluation of their Antimicrobial and Antifungal Activity

A series of thirteen (2E)-1-[4-({6-nitro-2-[(E)-2-phenylvinyl]quinolin-4-yl}amino)phenyl]- 3-[(substituted) phenyl]prop-2-en-1-ones (5a-5m) were synthesized by five-step synthesis starting from 4-nitroaniline via 2-methyl-6-nitroquinolin-4-ol (2), 4-chloro-2-methyl-6-nitroquinoline (3), 4- chloro-6-nitro-2-[(E)-2-phenylethenyl]quinoline (3), and 1-[4-({6-nitro-2-[(E)-2-phenylvinyl]quinolin- 4-yl}amino)phenyl]ethanone (5), respectively. Final chalcones 6a-6m were synthetized from 4 by condensation reaction with corresponding benzaldehydes (unsubstituted, 2-, 3- and 4-methyl-, 2-, 3- and 4-methoxy-, 2- and 4-fluoro-, 2-, 3- and 4-chloro-, and 4-trifluoromethylbenzaldehyde, respectively). Chalcones 6a-6m were characterized by IR, 1H NMR and MS spectroscopy deflate, is not presented. Antimicrobial and antifungal activity of the compound 6 was studied against the four bacterial types (Staphylococcus aureus MTCC 96, Streptococcus pyogenes MTCC 443, Escherichia coli MTCC 442, Pseudomonas aeruginosa MTCC 441) and three different types fungal strains (Aspergillus niger MTCC 282, Aspergillus clavatus MTCC1323, Candida albicans MTCC 227). From the above synthesized compounds the chalcones 6e, 6f, 6k, and 6m exhibited very good activity against studied gram-positive and gram-negative bacterial strains and compounds 6a, 6e, 6f, 6j 6k and 6m showed very good anti-fungal activity against fungi above. Keywords: Chalcone, quinoline, antibacterial, claisen–schmidt condensation, benzaldehyde, 4-aminoacetophenone.

Mycobacterium tuberculosis LppM Displays an Original Structure and Domain Composition Linked to a Dual Localization

Mycobacterium tuberculosis (Mtb) encodes several bacterial effectors impacting the colonization of phagocytes. LppM (Rv2171) is both implicated in phagocytosis and able to efficiently block phagosomal acidification in the macrophage, two key processes contributing to Mtb persistence. We show that LppM is anchored to the mycobacterial cell wall by a C-terminal membrane domain. However, the protein also exists as a truncated protein secreted into the culture medium. The LppM solution structure we solve here displays no similarity with other Mtb lipoproteins also involved in phagosomal maturation (i.e., LprG). In addition, we demonstrate that the protein may be able to bind rare molecular species of phosphatidylinositol mannosides, bacterial compounds known to affect the host immune response. Thus, our data demonstrate a dual localization of LppM and provide a unique perspective on the regulation of protein secretion and localization in Mtb.

A Proteomic Approach to Lipo-Chitooligosaccharide and Thuricin 17 Effects on Soybean GerminationUnstressed and Salt Stress.

Salt stress is an important abiotic stressor affecting crop growth and productivity. Of the 20 percent of the terrestrial earth’s surface available as agricultural land, 50 percent is estimated by the United Nations Environment Program to be salinized to the level that crops growing on it will be salt-stressed. Increased soil salinity has profound effects on seed germination and germinating seedlings as they are frequently confronted with much higher salinities than vigorously growing plants, because germination usually occurs in surface soils, the site of greatest soluble salt accumulation. The growth of soybean exposed to 40 mM NaCl is negatively affected, while an exposure to 80 mM NaCl is often lethal. When treated with the bacterial signal compounds lipo-chitooligosaccharide (LCO) and thuricin 17 (Th17), soybean seeds (variety Absolute RR) responded positively at salt stress of up to 150 mM NaCl. Shotgun proteomics of unstressed and 100 mM NaCl stressed seeds (48 h) in combination with the LCO and Th17 revealed many known, predicted, hypothetical and unknown proteins. In all, carbon, nitrogen and energy metabolic pathways were affected under both unstressed and salt stressed conditions when treated with signals. PEP carboxylase, Rubisco oxygenase large subunit, pyruvate kinase, and isocitrate lyase were some of the noteworthy proteins enhanced by the signals, along with antioxidant glutathione-S-transferase and other stress related proteins. These findings suggest that the germinating seeds alter their proteome based on bacterial signals and on stress, the specificity of this response plays a crucial role in organ maturation and transition from one stage to another in the plants' life cycle; understanding this response is of fundamental importance in agriculture and, as a result, global food security. The mass spectrometry proteomics data have been deposited to the ProteomeXchange with identifier PXD004106.

Elaboration of a proprietary thymidylate kinase inhibitor motif towards anti-tuberculosis agents

We report the design and synthesis of a series of non-nucleoside MtbTMPK inhibitors (1–14) based on the gram-positive bacterial TMPK inhibitor hit compound 1. A practical synthesis was developed to access these analogues. Several compounds show promising MtbTMPK inhibitory potency and allow the establishment of a structure–activity relationship, which is helpful for further optimization.