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Microbial Pathogenesis Jun 2024The present study explores the bioinspired green synthesis of zinc oxide nanoparticles (ZnONPs) using marine Streptomyces plicatus and its potent antibacterial,...
The present study explores the bioinspired green synthesis of zinc oxide nanoparticles (ZnONPs) using marine Streptomyces plicatus and its potent antibacterial, antibiofilm activity against dental caries forming Streptococcus mutans MTCC and S. mutans clinical isolate (CI), cytotoxicity against oral KB cancer cells, hemolysis against blood erythrocytes and artemia toxicity. The bioinspired ZnONPs showed a distinctive absorption peak at 375 nm in UV-Vis spectra, the FT-IR spectra divulged the active functional groups, and XRD confirmed the crystalline nature of the nanoparticles with an average grain size of 41.76 nm. SEM analysis evidenced hexagonal morphology, and EDX spectra affirmed the presence of zinc. The ZnONPs exerted higher antagonistic activity against S. mutans MTCC (Inhibitory zone: 19 mm; MIC: 75 μg/ml) than S. mutans CI (Inhibitory zone: 17 mm; MIC: 100 μg/ml). Results of biofilm inhibitory activity showed a concentration-dependent reduction with S. mutans MTCC (15 %-95 %) more sensitive than S. mutans CI (13 %-89 %). The 50 % biofilm inhibitory concentration (BIC) of ZnONPs against S. mutans MTCC was considerably lower (71.76 μg/ml) than S. mutans CI (78.13 μg/ml). Confocal Laser Scanning Microscopic visuals clearly implied that ZnONPs effectively distorted the biofilm architecture of both S. mutans MTCC and S. mutans CI. This was further bolstered by a remarkable rise in protein leakage (19 %-85 %; 15 %-77 %) and a fall in exopolysaccharide production (34 mg-7 mg; 49 mg-12 mg). MTT cytotoxicity of ZnONPs recorded an IC value of 22.06 μg/ml against KB cells. Acridine orange/ethidium bromide staining showed an increasing incidence of apoptosis in KB cells. Brine shrimp cytotoxicity using Artemia salina larvae recorded an LC value of 78.41 μg/ml. Hemolysis assay substantiated the biocompatibility of the ZnONPs. This study underscores the multifaceted application of bioinspired ZnONPs in dentistry.
PubMed: 38906493
DOI: 10.1016/j.micpath.2024.106758 -
Environmental Pollution (Barking, Essex... Jun 2024Diazinon is an organophosphorus pesticide widely used in agriculture and household pest control, and its use also poses several environmental and health hazards. In this...
Diazinon is an organophosphorus pesticide widely used in agriculture and household pest control, and its use also poses several environmental and health hazards. In this study, we investigated the spatial and temporal distribution of diazinon in Baiyangdian, evaluated its potential ecological risk and toxicity to aquatic organisms based on RQ (Risk quotient) and TU (Toxic unit) analysis, and assessed the potential effects of diazinon accumulation on probiotics and pathogens based on statistical analysis of high-throughput sequencing data. The results showed that diazinon in Baiyangdian posed a low to moderate chronic risk to sediment-dwelling organisms and a low toxicity effect on aquatic invertebrates, which was mainly concentrated in October and human-intensive areas. Meanwhile, increases in sediment electrical conductivity (EC), amorphous iron oxides content and phenol oxidase activity favored diazinon accumulation in sediments, whereas the opposite was the case for sediment organic carbon, β-1,4-glucosidase, phosphatase, catalase and pH, suggesting that environmental indicators play a key role in the behavior and distribution of diazinon. In addition, diazinon in heavily contaminated areas seem to inhibit the rare probiotics (Bifidobacterium adolescentis and Serratia sp.), while promoted dominant pathogens (e.g., Burkholderia cenocepacia), which can lead to increased disease risk to humans and ecosystems, disruption of ecological balance and potential health problems. However, probiotic Streptomyces xiamenensis resist to diazinon would be a potential degrader for diazinon remove. In conclusion, this study unveiled the effects of diazinon pollution on wetland ecosystems, emphasizing ecological impacts and potential health concerns. In addition, the discovery of diazinon resistant probiotics provided new insights into wetland ecological restoration.
PubMed: 38906403
DOI: 10.1016/j.envpol.2024.124408 -
Applied and Environmental Microbiology Jun 2024Precursor supply plays a significant role in the production of secondary metabolites. In bacteria, propionyl-, malonyl-, and methylmalonyl-CoA are the most common...
UNLABELLED
Precursor supply plays a significant role in the production of secondary metabolites. In bacteria, propionyl-, malonyl-, and methylmalonyl-CoA are the most common precursors used for polyketide biosynthesis. Although propionyl-CoA synthetases participate in the propionate assimilation pathway and directly convert propionate into propionyl-CoA, malonyl- and methylmalonyl-CoA cannot be formed using common acyl-CoA synthetases. Therefore, both acetyl- and propionyl-CoA carboxylation, catalyzed by acyl-CoA carboxylases, should be considered when engineering a microorganism chassis to increase polyketide production. In this study, we identified a transcriptional regulator of the TetR family, BkdR, in B4, which binds directly to the promoter region of the neighboring operon. This operon encodes acetyl/propionyl-CoA carboxylase and negatively regulates its transcription. In addition to acetate and propionate, the binding of BkdR to is disrupted by acetyl- and propionyl-CoA ligands. We identified a 16-nucleotide palindromic BkdR-binding motif (GTTAg/CGGTCg/TTAAC) in the intergenic region between and . When was deleted, we found an enhanced supply of malonyl- and methylmalonyl-CoA precursors in B4. In this study, spinosad production was detected in the recombinant strain after introducing the entire artificial biosynthesized gene cluster into B4. When supplemented with propionate to provide propionyl-CoA, the novel -deleted strain produced 29.4% more spinosad than the initial strain in trypticase soy broth (TSB) medium.
IMPORTANCE
In this study, we describe a operon involved in short-chain acyl-CoA carboxylation in B4 chassis. The TetR family regulator, BkdR, represses this operon. Our results show that BkdR regulates the precursor supply needed for heterologous spinosad biosynthesis by controlling acetyl- and propionyl-CoA assimilation. The deletion of the BkdR-encoding gene exerts an increase in heterologous spinosad yield. Our research reveals a regulatory mechanism in short-chain acyl-CoA metabolism and suggests new possibilities for chassis engineering to enhance heterologous polyketide yield.
PubMed: 38904409
DOI: 10.1128/aem.00838-24 -
Chemical Science Jun 2024The thioether-connected bis-amino acid lanthionine (Lan) residues are class-defining residues of lanthipeptides. Typically, the cyclization step of lanthionine...
The thioether-connected bis-amino acid lanthionine (Lan) residues are class-defining residues of lanthipeptides. Typically, the cyclization step of lanthionine formation, which relies on the addition of a cysteine to an unsaturated dehydroamino acid, is directed either by a standalone cyclase LanC (class I) or by a cyclase domain (class II-IV). However, the pathways of characterized class V members often lack a known cyclase (domain), raising a question on the mechanism by which their multi-macrocycle systems are formed. Herein, we report a new RiPP gene cluster in TN 58, where it encodes the biosynthesis of 3 distinct class V lanthipeptides-termed triantimycins (TAMs). TAM A1∼A3 share an N-terminal ll-MeLan residue, and only TAM A1 contains an additional internal ll-Lan residue. TAM A1 also has a C-terminal (2, 3)--(()-2-aminovinyl)-3-methyl-d-cysteine (AviMeCys) residue, which is distinct from the previously reported (2, 3)-AviMeCys residue in other RiPPs. Gene deletion, heterologous coexpression, and structural elucidation demonstrated that the cyclization for an ll-MeLan formation occurs spontaneously and is independent of any known lanthionine cyclase. This study provides a new paradigm for lanthionine formation and facilitates genome mining and engineering efforts on RiPPs containing (Me)Lan and ()Avi(Me)Cys residues.
PubMed: 38903209
DOI: 10.1039/d4sc02302a -
Bioorganic Chemistry Jun 2024The fast spread of antibiotic resistance results in the requirement for a constant introduction of new candidates. Pentangular polyphenols, a growing family of... (Review)
Review
The fast spread of antibiotic resistance results in the requirement for a constant introduction of new candidates. Pentangular polyphenols, a growing family of actinomycetes-derived aromatic type II polyketides, have attracted considerable attention due to their intriguing polycyclic systems and potent antimicrobial activity. Among them, benastatins, anthrabenzoxocinones (ABXs), and fredericamycins, display unique variations in their polycyclic frameworks, yet concurrently share structural commonalities within their substitutions. The present review summarizes advances in the isolation, spectroscopic characteristics, biosynthesis, and biological activities of pentangular polyphenols benastatins (1-16), ABXs (17-39), and fredericamycins (40-42) from actinomycetes. The information presented here thus prompts researchers to further explore and discover additional congeners within these three small classes of pentangular polyphenols.
PubMed: 38901281
DOI: 10.1016/j.bioorg.2024.107572 -
Foodborne Pathogens and Disease Jun 2024Methicillin-resistant (MRSA) can easily form biofilms on food surfaces, thus leading to cross-contamination, which is difficult to remove. Therefore, there is an urgent...
Methicillin-resistant (MRSA) can easily form biofilms on food surfaces, thus leading to cross-contamination, which is difficult to remove. Therefore, there is an urgent need to find alternatives with good antibacterial and antibiofilm effects. In this study, two indole sesquiterpene compounds, xiamycin () and chlorinated metabolite chloroxiamycin (), were isolated from the fermentation liquid of marine sp. NBU3429 for the first time. The chemical structures of the two compounds were characterized by spectroscopic data interpretation, including 1D NMR and HRESIMS analysis. Antimicrobial test showed that chloroxiamycin () (minimum inhibitory concentration, MIC = 16 μg/mL) exhibited superior antibacterial activity than xiamycin () (MIC = 32 μg/mL) against MRSA ATCC43300. Moreover, compound () decreased the biofilm formation rate of MRSA ATCC43300 by 12.7%-84.6% in the concentration range of 32-512 μg/mL, which is relatively stronger than xiamycin () (4.1%-49.9%) as well. Antibacterial/antibiofilm mechanism investigation indicated that chloroxiamycin () could disrupt the cell wall and membrane of MRSA, inhibiting the production of biofilm extracellular polysaccharides. All these results illustrated that chloroxiamycin () is an effective antibacterial/antibiofilm agent, which makes it an attractive candidate for food preservatives.
PubMed: 38900687
DOI: 10.1089/fpd.2024.0003 -
Journal of Agricultural and Food... Jun 2024Potato common scab (PCS) is a widespread plant disease that lacks effective control measures. Using a small molecule elicitor, we activate the production of a novel...
Potato common scab (PCS) is a widespread plant disease that lacks effective control measures. Using a small molecule elicitor, we activate the production of a novel class of polyketide antibiotics, streptolateritic acids A-D, in sp. FXJ1.172. These compounds show a promising control efficacy against PCS and an unusual acyclic pentacarboxylic acid structure. A gene cluster encoding a type I modular polyketide synthase is identified to be responsible for the biosynthesis of these metabolites. A cytochrome P450 (CYP) and an aldehyde dehydrogenase (ADH) encoded by two genes in the cluster are proposed to catalyze iterative oxidation of the starter-unit-derived methyl group and three of six branching methyl groups to carboxylic acids during chain assembly. Our findings highlight how activation of silent biosynthetic gene clusters can be employed to discover completely new natural product classes able to combat PCS and new types of modular polyketide synthase-based biosynthetic machinery.
PubMed: 38899439
DOI: 10.1021/acs.jafc.4c02572 -
Angewandte Chemie (International Ed. in... Jun 2024Recent advances in whole genome sequencing have revealed an immense microbial potential for the production of therapeutic small molecules, even from well-known...
Recent advances in whole genome sequencing have revealed an immense microbial potential for the production of therapeutic small molecules, even from well-known producers. To access this potential, we subjected prominent antimicrobial producers to alternative antiproliferative assays using persistent cancer cell lines. Described herein is our discovery of hirocidins, novel secondary metabolites from Streptomyces hiroshimensis with antiproliferative activities against colon and persistent breast cancer cells. Hirocidin A is an unusual nine-membered carbocyclic maleimide and hirocidins B and C are relatives with an unprecedented, bridged azamacrocyclic backbone. Mode of action studies show that hirocidins trigger mitochondrion-dependent apoptosis by inducing expression of the key apoptotic effector caspase-9. The discovery of new cytotoxins contributes to scaffold diversification in anticancer drug discovery and the reported modes of action and concise total synthetic route for variant A set the stage for unraveling specific targets and biochemical interactions of the hirocidins.
PubMed: 38898540
DOI: 10.1002/anie.202405367 -
The ISME Journal Jun 2024The rhizosphere, which serves as the primary interface between plant roots and the soil, constitutes an ecological niche for a huge diversity of microbial communities....
The rhizosphere, which serves as the primary interface between plant roots and the soil, constitutes an ecological niche for a huge diversity of microbial communities. Currently, there is little knowledge on the nature and the function of the different metabolites released by rhizospheric microbes to facilitate colonization of this highly competitive environment. Here, we demonstrate how the production of galbonolides, a group of polyene macrolides that inhibit plant and fungal inositol phosphorylceramide synthase (IPCS), empowers the rhizospheric Streptomyces strain AgN23, to thrive in the rhizosphere by triggering the plant's defence mechanisms. Metabolomic analysis of AgN23-inoculated Arabidopsis roots revealed a strong induction in the production of an indole alkaloid, camalexin, which is a major phytoalexin in Arabidopsis. By using a plant mutant compromized in camalexin synthesis, we show that camalexin production is necessary for the successful colonization of the rhizosphere by AgN23. Conversely, hindering galbonolides biosynthesis in AgN23 knock-out mutant resulted in loss of inhibition of IPCS, a deficiency in plant defence activation, notably the production of camalexin, and a strongly reduced development of the mutant bacteria in the rhizosphere. Together, our results identified galbonolides as important metabolites mediating rhizosphere colonization by Streptomyces.
PubMed: 38896026
DOI: 10.1093/ismejo/wrae112 -
ACS Catalysis Apr 2024A number of bacteria are known to produce isonitrile-containing peptides (INPs) that facilitate metal transport and are important for cell survival; however,...
A number of bacteria are known to produce isonitrile-containing peptides (INPs) that facilitate metal transport and are important for cell survival; however, considerable structural variation is observed among INPs depending on the producing organism. While non-heme iron 2-oxoglutarate dependent isonitrilases catalyze isonitrile formation, how the natural variation in INP structure is controlled and its implications for INP bioactivity remain open questions. Herein, total chemical synthesis is utilized with X-Ray crystallographic analysis of mycobacterial isonitrilases to provide a structural model of substrate specificity that explains the longer alkyl chains observed in mycobacterial versus Streptomyces INPs. Moreover, proton NMR titration experiments demonstrate that INPs regardless of alkyl chain length are specific for binding copper instead of zinc. These results suggest that isonitrilases may act as gatekeepers in modulating the observed biological distribution of INP structures and this distribution may be primarily related to differing metal transport requirements among the producing strains.
PubMed: 38895101
DOI: 10.1021/acscatal.4c00645