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Nature Communications Sep 2023Peptidoglycan (PG) defines cell shape and protects bacteria against osmotic stress. The growth and integrity of PG require coordinated actions between synthases that...
Peptidoglycan (PG) defines cell shape and protects bacteria against osmotic stress. The growth and integrity of PG require coordinated actions between synthases that insert new PG strands and hydrolases that generate openings to allow the insertion. However, the mechanisms of their coordination remain elusive. Moenomycin that inhibits a family of PG synthases known as Class-A penicillin-binding proteins (aPBPs), collapses rod shape despite aPBPs being non-essential for rod-like morphology in the bacterium Myxococcus xanthus. Here, we demonstrate that inhibited PBP1a2, an aPBP, accelerates the degradation of cell poles by DacB, a hydrolytic PG peptidase. Moenomycin promotes the binding between DacB and PG and thus reduces the mobility of DacB through PBP1a2. Conversely, DacB also regulates the distribution and dynamics of aPBPs. Our findings clarify the action of moenomycin and suggest that disrupting the coordination between PG synthases and hydrolases could be more lethal than eliminating individual enzymes.
Topics: Peptidoglycan; Bambermycins; Nitric Oxide Synthase; Peptide Hydrolases; Cell Wall; Myxococcus xanthus; Penicillin-Binding Proteins
PubMed: 37660104
DOI: 10.1038/s41467-023-41082-3 -
Folia Microbiologica Feb 2024Secondary metabolites produced by myxobacterial genera are often characterized as diverse molecules with unique structural properties which drove us to search for...
Secondary metabolites produced by myxobacterial genera are often characterized as diverse molecules with unique structural properties which drove us to search for myxobacterial source of anti-diabetic drug discovery. In the present study, from 80 soil samples, out of sixty-five observed isolates, 30 and 16 were purified as Myxococcus and non-Myxococcus, respectively. Isolated strains taxonomically belonged to the genera Myxococcus, Corallococcus and Cystobacter, Archangium, Nanocystis, and Sorangium, and some could not be attributed. Secondary metabolites of selected non-Myxococcus isolates extracted by the liquid-liquid method showed that the myxobacterium UTMC 4530 demonstrated the highest inhibition on the formation of carbonyl group and fructosamine, respectively. In addition, it showed 23% and 15.8% inhibitory activity on α-glucosides and α-amylase compared to acarbose (23%, 18%), respectively. The extract of strain UTMC 4530 showed 35% induction effect on glucose adsorption while showing no radical scavenging activity and no toxic effect on HRBC lysis and HepG2 in cytotoxicity assays. The strain UTMC 4530 (ON808962), with the multiple antidiabetic activity, showed 87.3% similarity to Corallococcus llansteffanensis which indicates its affiliation to a new genus. The results of this study revealed that secondary metabolites produced by strain UTMC 4530 can be considered a promising source to find new therapeutic and pharmaceutical applications perhaps a multi-mechanism anti-diabetic compound.
Topics: Myxococcales; Soil Microbiology; Soil; Phylogeny; Myxococcus
PubMed: 37477787
DOI: 10.1007/s12223-023-01074-8 -
Journal of the American Chemical Society Aug 2023The genomes of myxobacteria harbor a variety of biosynthetic gene clusters encoding numerous secondary metabolites, including ribosomally synthesized and...
The genomes of myxobacteria harbor a variety of biosynthetic gene clusters encoding numerous secondary metabolites, including ribosomally synthesized and post-translationally modified peptides (RiPPs) with diverse chemical structures and biological activities. However, the biosynthetic potential of RiPPs from myxobacteria remains barely explored. Herein, we report a novel myxobacteria lanthipeptide myxococin identified from . Myxococins represent the first example of lanthipeptides, of which the characteristic multiple thioether rings are installed by employing a Class II lanthipeptide synthetase MfuM and a Class I lanthipeptide cyclase MfuC in a cascaded way. Unprecedentedly, we biochemically characterized the first M61 family aminopeptidase MfuP involved in RiPP biosynthesis, demonstrating that MfuP showed the activity of an endopeptidase activity. MfuP is leader-independent but strictly selective for the multibridge structure of myxococin A and responsible for unwrapping two rings via amide bond hydrolysis, yielding myxococin B. Furthermore, the X-ray crystal structure of MfuP and structural analysis, including active-site mutations, are reported. Finally, myxococins are evaluated to exhibit anti-inflammatory activity in lipopolysaccharide-induced macrophages without detectable cytotoxicity.
Topics: Myxococcales; Peptides; Protein Processing, Post-Translational
PubMed: 37466996
DOI: 10.1021/jacs.3c06014 -
Nature Communications Jul 2023During cell migration, front-rear polarity is spatiotemporally regulated; however, the underlying design of regulatory interactions varies. In rod-shaped Myxococcus...
During cell migration, front-rear polarity is spatiotemporally regulated; however, the underlying design of regulatory interactions varies. In rod-shaped Myxococcus xanthus cells, a spatial toggle switch dynamically regulates front-rear polarity. The polarity module establishes front-rear polarity by guaranteeing front pole-localization of the small GTPase MglA. Conversely, the Frz chemosensory system, by acting on the polarity module, causes polarity inversions. MglA localization depends on the RomR/RomX GEF and MglB/RomY GAP complexes that localize asymmetrically to the poles by unknown mechanisms. Here, we show that RomR and the MglB and MglC roadblock domain proteins generate a positive feedback by forming a RomR/MglC/MglB complex, thereby establishing the rear pole with high GAP activity that is non-permissive to MglA. MglA at the front engages in negative feedback that breaks the RomR/MglC/MglB positive feedback allosterically, thus ensuring low GAP activity at this pole. These findings unravel the design principles of a system for switchable front-rear polarity.
Topics: Myxococcus xanthus; Bacterial Proteins; Cell Movement; Monomeric GTP-Binding Proteins; Cell Polarity
PubMed: 37422455
DOI: 10.1038/s41467-023-39773-y -
Journal of Microbiological Methods Aug 2023Myxobacteria have potential application value in developing new antibiotics and environmental protection. In this study, in order to establish a more suitable method for...
Myxobacteria have potential application value in developing new antibiotics and environmental protection. In this study, in order to establish a more suitable method for diversity studies of myxobacteria, the effects of primers, polymerase chain reaction (PCR) approaches and sample preservation methods on the results were compared by Illumina high-throughput sequencing. The results showed that the relative abundance and operational taxonomic unit (OTU) ratio of myxobacteria amplified by the universal primers accounted for 0.91-1.85% and 2.82-4.10% of total bacteria, indicating that myxobacteria were the dominant bacteria both in population and species numbers. The relative abundance and OTU number and ratio of myxobacteria amplified by the myxobacteria semi-specific primers were significantly higher than those amplified by the universal primers, of which the primer pair W2/802R specifically amplified myxobacteria of suborder Cystobacterineae, while the primer pair W5/802R mainly amplified myxobacteria of suborder Sorangineae and also amplified more species of suborder Nannocystineae at the same time. Among three PCR approaches, the relative abundance and OTU ratio of myxobacteria amplified by the touch-down PCR were the highest. More myxobacterial OTUs were detected in most dried samples. In conclusion, the combination of the myxobacteria semi-specific primer pairs W2/802R and W5/802R, touch-down PCR, and dry preservation of samples were more conducive to diversity studies of myxobacteria.
Topics: Myxococcales; Soil Microbiology; Bacteria; Polymerase Chain Reaction
PubMed: 37379888
DOI: 10.1016/j.mimet.2023.106774 -
Microbiology Spectrum Aug 2023Polyp bail-out constitutes both a stress response and an asexual reproductive strategy that potentially facilitates dispersal of some scleractinian corals, including...
Polyp bail-out constitutes both a stress response and an asexual reproductive strategy that potentially facilitates dispersal of some scleractinian corals, including several dominant reef-building taxa in the family Pocilloporidae. Recent studies have proposed that microorganisms may be involved in onset and progression of polyp bail-out. However, changes in the coral microbiome during polyp bail-out have not been investigated. In this study, we induced polyp bail-out in corals using hypersaline and hyperthermal methods. Bacterial community dynamics during bail-out induction were examined using the V5-V6 region of the 16S-rRNA gene. From 70 16S-rRNA gene libraries constructed from coral tissues, 1,980 OTUs were identified. and consistently constituted the dominant bacterial taxa in all coral tissue samples. Onset of polyp bail-out was characterized by increased relative abundance of and decreased abundance of in both induction experiments, with the shift being more prominent in response to elevated temperature than to elevated salinity. Four OTUs, affiliated with , , , and , showed concurrent abundance increases at the onset of polyp bail-out in both experiments, suggesting potential microbial causes of this coral stress response. Polyp bail-out represents both a stress response and an asexual reproductive strategy with significant implications for reshaping tropical coral reefs in response to global climate change. Although earlier studies have suggested that coral-associated microbiomes likely contribute to initiation of polyp bail-out in scleractinian corals, there have been no studies of coral microbiome shifts during polyp bail-out. In this study, we present the first investigation of changes in bacterial symbionts during two experiments in which polyp bail-out was induced by different environmental stressors. These results provide a background of coral microbiome dynamics during polyp bail-out development. Increases in abundance of , , , and that occurred in both experiments suggest that these bacteria are potential microbial causes of polyp bail-out, shedding light on the proximal triggering mechanism of this coral stress response.
Topics: Animals; Anthozoa; Coral Reefs; Microbiota; Gammaproteobacteria; Rhodobacteraceae; Myxococcales; RNA, Ribosomal, 16S
PubMed: 37378544
DOI: 10.1128/spectrum.00257-23 -
Microbiology Spectrum Aug 2023Myxobacteria serve as a treasure trove of secondary metabolites. During our ongoing search for bioactive natural products, a novel subclass of disorazoles termed...
Myxobacteria serve as a treasure trove of secondary metabolites. During our ongoing search for bioactive natural products, a novel subclass of disorazoles termed disorazole Z was discovered. Ten disorazole Z family members were purified from a large-scale fermentation of the myxobacterium Sorangium cellulosum So ce1875 and characterized by electrospray ionization-high-resolution mass spectrometry (ESI-HRMS), X-ray, nuclear magnetic resonance (NMR), and Mosher ester analysis. Disorazole Z compounds are characterized by the lack of one polyketide extension cycle, resulting in a shortened monomer in comparison to disorazole A, which finally forms a dimer in the bis-lactone core structure. In addition, an unprecedented modification of a geminal dimethyl group takes place to form a carboxylic acid methyl ester. The main component disorazole Z1 shows comparable activity in effectively killing cancer cells to disorazole A1 via binding to tubulin, which we show induces microtubule depolymerization, endoplasmic reticulum delocalization, and eventually apoptosis. The disorazole Z biosynthetic gene cluster (BGC) was identified and characterized from the alternative producer So ce427 and compared to the known disorazole A BGC, followed by heterologous expression in the host Myxococcus xanthus DK1622. Pathway engineering by promoter substitution and gene deletion paves the way for detailed biosynthesis studies and efficient heterologous production of disorazole Z congeners. Microbial secondary metabolites are a prolific reservoir for the discovery of bioactive compounds, which prove to be privileged scaffolds for the development of new drugs such as antibacterial and small-molecule anticancer drugs. Consequently, the continuous discovery of novel bioactive natural products is of great importance for pharmaceutical research. Myxobacteria, especially spp., which are known for their large genomes with yet-underexploited biosynthetic potential, are proficient producers of such secondary metabolites. From the fermentation broth of Sorangium cellulosum strain So ce1875, we isolated and characterized a family of natural products named disorazole Z, which showed potent anticancer activity. Further, we report on the biosynthesis and heterologous production of disorazole Z. These results can be stepping stones toward pharmaceutical development of the disorazole family of anticancer natural products for (pre)clinical studies.
Topics: Biological Products; Antineoplastic Agents; Lactones; Myxococcales
PubMed: 37318329
DOI: 10.1128/spectrum.00730-23 -
Research in Microbiology 2023Myxobacteria are Gram-negative eubacteria and they thrive in a variety of habitats including soil rich in organic matter, rotting wood, animal dung and marine... (Review)
Review
Myxobacteria are Gram-negative eubacteria and they thrive in a variety of habitats including soil rich in organic matter, rotting wood, animal dung and marine environment. Myxobacteria are a promising source of new compounds associated with diverse bioactive spectrum and unique mode of action. The genome information of myxobacteria has revealed many orphan biosynthetic pathways indicating that these bacteria can be the source of several novel natural products. In this review, we highlight the biology of myxobacteria with emphasis on their habitat, life cycle, isolation methods and enlist all the bioactive secondary metabolites purified till date and their mode of action.
Topics: Animals; Myxococcales; Bacteria; Biology; Biological Products
PubMed: 37169232
DOI: 10.1016/j.resmic.2023.104079 -
Environmental Pollution (Barking, Essex... Jul 2023The microbial reduction of NO serves as a "gatekeeper" for NO emissions, determining the flux of NO release into the atmosphere. Estuaries are active regions for NO...
The microbial reduction of NO serves as a "gatekeeper" for NO emissions, determining the flux of NO release into the atmosphere. Estuaries are active regions for NO emissions, but the microbial functions of NO-reducing bacteria in estuarine ecosystems are not well understood. In this study, the N isotope tracer method, qPCR, and high-throughput sequencing were used to analyze NO production, reduction, and emission processes in surface sediments of the Pearl River Estuary. The N isotope tracer experiment showed that the NO production rates declined and the NO reduction potential (R, the ratio of NO reduction rates to NO production rates) increased from upstream to downstream of the Pearl River Estuary, leading to a corresponding decrease of the NO emission rates from upstream to downstream. The gene abundance ratio of nosZ/nir gradually increased from upstream to downstream and was negatively correlated with the water NO saturation. The gene abundance of nosZ II was significantly higher than that of nosZ I in the estuary, and the nosZ II/nosZ I abundance ratio was positively correlated with NO reduction potential. Furthermore, the community composition of NosZ-I- and NosZ-II-type NO-reducing bacteria shifted from upstream to downstream. NosZ-II-type NO-reducing bacteria, especially Myxococcales, Thiotrichales, and Gemmatimonadetes species, contributed to the high NO reduction potential in the downstream. Our results suggest that NosZ-II-type NO-reducing bacteria play a dominant role in determining the release potential of NO from sediments in the Pearl River Estuary. This study provides a new insight into the function of microbial NO reduction in estuarine ecosystems.
Topics: Estuaries; Ecosystem; Nitrous Oxide; Bacteria; Rivers; China; Denitrification
PubMed: 37116571
DOI: 10.1016/j.envpol.2023.121732