Myxobacteria are soil-dwelling, Gram-negative bacteria which are notable not only for their multi-cellular 'social' lifestyles, but for production of structurally diverse secondary metabolites with ...potential in clinical therapy. Here we briefly review the history of myxobacterial natural products research, provide an overview of their unique secondary metabolism, with an emphasis on assembly line biosynthesis of polyketide and non-ribosomal peptide metabolites, and look to the future of the field.
Cruentaren A, a new antifungal benzolactone produced by the myxobacterium Byssovorax cruenta, proved to be highly cytotoxic against various human cell lines. It inhibited the proliferation of ...different cancer cell lines including a multidrug-resistant KB line at low nanomolar levels. It arrested human histocytic lymphoma cells (U-937) in G sub(0) sub(/) sub(1) phase, but did not trigger an apoptotic process. Studies to uncover the molecular target of cruentaren A showed that the novel compound, despite its structural similarity to the benzolactone enamides apicularen and salicylihalamide, was no V-ATPase inhibitor. In contrast, cruentaren specifically inhibited mitochondrial F sub(O)F sub(1)-ATPases with IC50 values of 15-30nM. Although the exact binding site of cruentaren remains undefined, inhibition was shown to occur by interaction with the catalytic F sub(1) domain. Since mitochondrial ATPases play a crucial role in the pathophysiology of several human disorders including cancer, cruentaren or synthetic derivatives thereof could form the basis of future therapeutic strategies.
Tubulysin A (tubA) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. The potential of tubA as an anticancer and ...antiangiogenic agent is explored in the present study. tubA shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. It induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic properties in several @@iin vitro@ assays. It is efficacious in initial animal studies using a hollow fibre assay with 12 different human tumour cell lines. This study suggests that both @@iin vitro@ and preclinical profiles of tubA may translate into clinically useful anticancer properties.
Myxobacteria are ubiquitous in agricultural soils and the rhizosphere of crop plants. They produce a plethora of diverse secondary metabolites, prey on bacteria and inhibit fungi, including plant ...pathogens. Mutations in early developmental regulatory and putative antibiotic production genes in M. xanthus DK1622 reduced control of soil-borne fungal pathogens in growth chamber assays. Additionally these mutants and well-characterized motility mutants were impaired for predation of plant pathogenic bacteria in in vitro assays. These data suggest that predation and development are dependent upon a series of interlinked processes required for myxobacterial nutrient scavenging. Because myxobacteria are difficult to enumerate from environmental samples, culture-independent methods of detection and enumeration of myxobacteria were developed and are being used to determine how these and other factors influence predation and disease control in situ. These methods are being used in conjunction with whole microbial community analysis methods to evaluate the impact of myxobacteria on fungal and bacterial populations in agricultural and undisturbed soils.
Myxobacteria are not only known for their complex “social behavior” including the formation of fruiting bodies, but also for being a prolific source of natural products. We describe the discovery and ...isolation of the myxofacycline natural product family, which feature either an isoxazole, a 4‐pyrimidinole or a 1,2‐dihydropyrrol‐3‐one heterocycle. Intriguingly, mutagenesis of the producer strain and heterologous expression of the identified biosynthetic genes revealed that all three heterocycles originate from the same biosynthetic pathway, thus suggesting an unique biochemistry to synthesize (secondary) metabolites with exceptional scaffolds and heterocycles. More information can be found in the Full Paper by R. Müller et al. (DOI: 10.1002/chem.202103095).
Abstract
Members of the predatory Myxococcales (myxobacteria) possess large genomes, undergo multicellular development, and produce diverse secondary metabolites, which are being actively prospected ...for novel drug discovery. To direct such efforts, it is important to understand the relationships between myxobacterial ecology, evolution, taxonomy, and genomic variation.
This study investigated the genomes and pan-genomes of organisms within the Myxococcaceae, including the genera Myxococcus and Corallococcus, the most abundant myxobacteria isolated from soils. Previously, ten species of Corallococcus were known, whereas six species of Myxococcus phylogenetically surrounded a third genus (Pyxidicoccus) composed of a single species. Here, we describe draft genome sequences of five novel species within the Myxococcaceae (Myxococcus eversor, Myxococcus llanfairpwllgwyngyllgogerychwyrndrobwllllantysiliogogogochensis, Myxococcus vastator, Pyxidicoccus caerfyrddinensis, and Pyxidicoccus trucidator) and for the Pyxidicoccus type species strain, Pyxidicoccus fallax DSM 14698T. Genomic and physiological comparisons demonstrated clear differences between the five novel species and every other Myxococcus or Pyxidicoccus spp. type strain.
Subsequent analyses of type strain genomes showed that both the Corallococcus pan-genome and the combined Myxococcus and Pyxidicoccus (Myxococcus/Pyxidicoccus) pan-genome are large and open, but with clear differences. Genomes of Corallococcus spp. are generally smaller than those of Myxococcus/Pyxidicoccus spp. but have core genomes three times larger. Myxococcus/Pyxidicoccus spp. genomes are more variable in size, with larger and more unique sets of accessory genes than those of Corallococcus species. In both genera, biosynthetic gene clusters are relatively enriched in the shell pan-genomes, implying they grant a greater evolutionary benefit than other shell genes, presumably by conferring selective advantages during predation.
Bacterial predation: 75 years and counting Pérez, Juana; Moraleda-Muñoz, Aurelio; Marcos-Torres, Francisco Javier ...
Environmental microbiology,
March 2016, Letnik:
18, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
The first documented study on bacterial predation was carried out using myxobacteria three quarters of a century ago. Since then, many predatory strains, diverse hunting strategies, ...environmental consequences and potential applications have been reported by groups all over the world. Now we know that predatory bacteria are distributed in a wide variety of environments and that interactions between predatory and non‐predatory populations seem to be the most important factor in bacterial selection and mortality in some ecosystems. Bacterial predation has now been proposed as an evolutionary driving force. The structure and diversity of the predatory bacterial community is beginning to be recognized as an important factor in biodiversity due to its potential role in controlling and modelling bacterial populations in the environment. In this paper, we review the current understanding of bacterial predation, going over the strategies used by the main predatory bacteria to kill their prey. We have also reviewed and integrated the accumulated advances of the last 75 years with the interesting new insights that are provided by the analyses of genomes, predatomes, predatosomes and other comparative genomics studies, focusing on potential applications that derive from all of these areas of study.
is an abundant genus of predatory soil myxobacteria, containing two species,
(for which a genome sequence is available) and
. To investigate the genomic basis of predation, we genome-sequenced 23
...strains. Genomic similarity metrics grouped the sequenced strains into at least nine distinct genomospecies, divided between two major sub-divisions of the genus, encompassing previously described diversity. The
pan-genome was found to be open, with strains exhibiting highly individual gene sets. On average, only 30.5% of each strain's gene set belonged to the core pan-genome, while more than 75% of the accessory pan-genome genes were present in less than four of the 24 genomes. The
accessory pan-proteome was enriched for the COG functional category "Secondary metabolism," with each genome containing on average 55 biosynthetic gene clusters (BGCs), of which only 20 belonged to the core pan-genome. Predatory activity was assayed against ten prey microbes and found to be mostly incongruent with phylogeny or BGC complement. Thus, predation seems multifactorial, depending partially on BGC complement, but also on the accessory pan-genome - genes most likely acquired horizontally. These observations encourage further exploration of
as a source for novel bioactive secondary metabolites and predatory proteins.
Yen NTN, Chung DD, Hong NTK, Cham NP, Nhan VT, Linh DTL, Ngoc NLB, Thai NM, Nga ND, Anh NT. 2023. Isolation, phylogenetic analysis and bioprospection of myxobacteria from Vietnam. Biodiversitas 24: ...5653-5663. Myxobacteria have been considered microbial factories for producing secondary metabolites that have a variety of potential biological actions for discovering and isolating new biological molecules. Myxobacteria were isolated from soil samples collected in some provinces/cities in Vietnam. The purified isolates were identified based on morphology, biochemical test and phylogenetic analysis inferred from 16S rRNA gene. High-throughput screening assays including 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DDPH) for antioxidant properties and microdilution for antimicrobial activity were performed with myxobacterial extracts. Compounds from potential strain were predicted using liquid chromatography coupled with mass spectrometry. Forty-three myxobacterial strains were isolated and classified into seven genera of Angiococcus, Archangium, Chondromyces, Corallococcus, Cystobacter, Melittangium, and Myxococcus. The extract from CT21 strain had the highest total antioxidant activity (IC50 = 52.34 ± 1.47 and 30.28 ± 0.74 ?g/mL for the DPPH and ABTS, respectively). It is worth noting that all strains isolated myxobacterial strains show inhibitory activity against at least one of the tested microorganisms. The most potent antimicrobial strain was Myxococcus stipitatus GL41, which inhibited all tested microorganisms, and the minimal inhibitory concentration (MIC) values were 1 ?g/mL against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), Streptococcus faecalis, Candida albicans, and Aspergillus niger. Mass spectrometry analysis revealed the presence of althiomycin - the polyketide antibiotic from ethyl acetate fraction. In the present study, myxobacteria were isolated from soil sample collected from Vietnam, analyzed phylogenetically, and screened for biological activities.
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.
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