RESUMEN
Multicellular magnetotactic bacteria (MMB) have a surprisingly complex multicellular lifestyle. A new study in PLOS Biology combines genomics, microscopy, and isotopic labeling to show that MMB form obligately multicellular consortia of genetically diverse cells with rudimentary division of labor.
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Bacterias , Bacterias/genética , Bacterias/metabolismo , Magnetospirillum/metabolismo , Magnetospirillum/fisiología , Magnetospirillum/genética , Magnetospirillum/citología , Magnetosomas/metabolismoRESUMEN
While significant advances have been made in exploring and uncovering the promising potential of biomagnetic materials, persistent challenges remain on various fronts, notably in the characterization of individual elements. This study makes use of advanced modes of Magnetic Force Microscopy (MFM) and tailored MFM probes to characterize individual magnetotactic bacteria in different environments. The characterization of these elements posed a significant challenge, as the magnetosomes, besides presenting low magnetic signal, are embedded in bacteria of much larger size. To overcome this, customed Atomic Force Microscopy probes are developed through various strategies, enhancing sensitivity in different environments, including liquids. Furthermore, employing MFM imaging under an in-situ magnetic field provides an opportunity to gather quantitative data regarding the critical fields of these individual chains of nanoparticles. This approach marks a substantial advancement in the field of MFM for biological applications, enabling the detection of magnetosomes under different conditions.
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Magnetosomas , Microscopía de Fuerza Atómica , Magnetosomas/metabolismo , Magnetosomas/química , Magnetosomas/ultraestructura , Microscopía de Fuerza Atómica/métodos , Magnetospirillum/metabolismo , Campos MagnéticosRESUMEN
Magnetotactic bacteria are a diverse group of microbes that use magnetic particles housed within intracellular lipid-bounded magnetosome organelles to guide navigation along geomagnetic fields. The development of magnetosomes and their magnetic crystals in Magnetospirillum magneticum AMB-1 requires the coordinated action of numerous proteins. Most proteins are thought to localize to magnetosomes during the initial stages of organelle biogenesis, regardless of environmental conditions. However, the magnetite-shaping protein Mms6 is only found in magnetosomes that contain magnetic particles, suggesting that it might conditionally localize after the formation of magnetosome membranes. The mechanisms for this unusual mode of localization to magnetosomes are unclear. Here, using pulse-chase labeling, we show that Mms6 translated under non-biomineralization conditions translocates to pre-formed magnetosomes when cells are shifted to biomineralizing conditions. Genes essential for magnetite production, namely mamE, mamM, and mamO, are necessary for Mms6 localization, whereas mamN inhibits Mms6 localization. MamD localization was also investigated and found to be controlled by similar cellular factors. The membrane localization of Mms6 is dependent on a glycine-leucine repeat region, while the N-terminal domain of Mms6 is necessary for retention in the cytosol and impacts conditional localization to magnetosomes. The N-terminal domain is also sufficient to impart conditional magnetosome localization to MmsF, altering its native constitutive magnetosome localization. Our work illuminates an alternative mode of protein localization to magnetosomes in which Mms6 and MamD are excluded from magnetosomes by MamN until biomineralization initiates, whereupon they translocate into magnetosome membranes to control the development of growing magnetite crystals.IMPORTANCEMagnetotactic bacteria (MTB) are a diverse group of bacteria that form magnetic nanoparticles surrounded by membranous organelles. MTB are widespread and serve as a model for bacterial organelle formation and biomineralization. Magnetosomes require a specific cohort of proteins to enable magnetite formation, but how those proteins are localized to magnetosome membranes is unclear. Here, we investigate protein localization using pulse-chase microscopy and find a system of protein coordination dependent on biomineralization-permissible conditions. In addition, our findings highlight a protein domain that alters the localization behavior of magnetosome proteins. Utilization of this protein domain may provide a synthetic route for conditional functionalization of magnetosomes for biotechnological applications.
Asunto(s)
Proteínas Bacterianas , Magnetosomas , Magnetospirillum , Magnetospirillum/genética , Magnetospirillum/metabolismo , Magnetosomas/metabolismo , Magnetosomas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Regulación Bacteriana de la Expresión Génica , Transporte de ProteínasRESUMEN
Magnetotactic bacteria produce chains of nanoscopic iron minerals used for navigation, which can be preserved over geological timescales in the form of magnetofossils. Micrometer-sized magnetite crystals with unusual shapes suggesting a biologically controlled mineralization have been found in the geological record and termed giant magnetofossils. The biological origin and function of giant magnetofossils remains unclear, due to the lack of modern analogues to giant magnetofossils. Using distinctive Ptychographic nanotomography data of Precambrian (1.88 Ga) rocks, we recovered the morphology of micrometric cuboid grains of iron oxides embedded in an organic filamentous fossil to construct synthetic magnetosomes. Their morphology is different from that of previously found giant magnetofossils, but their occurrence in filamentous microfossils and micromagnetic simulations support the hypothesis that they could have functioned as a navigation aid, akin to modern magnetosomes.
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Fósiles , Magnetosomas , Magnetosomas/química , Magnetosomas/metabolismo , Óxido Ferrosoférrico/química , Sedimentos Geológicos/químicaRESUMEN
Bacterial species referred to as magnetotactic bacteria (MTB) biomineralize iron oxides and iron sulphides inside the cell. Bacteria can arrange themselves passively along geomagnetic field lines with the aid of these iron components known as magnetosomes. In this study, magnetosome nanoparticles, which were obtained from the taxonomically identified MTB isolate Providencia sp. PRB-1, were characterized and their antibacterial activity was evaluated. An in vitro test showed that magnetosome nanoparticles significantly inhibited the growth of Staphylococcus sp., Pseudomonas aeruginosa, and Klebsiella pneumoniae. Magnetosomes were found to contain cuboidal iron crystals with an average size of 42 nm measured by particle size analysis and scanning electron microscope analysis. The energy dispersive X-ray examination revealed that Fe and O were present in the extracted magnetosomes. The extracted magnetosome nanoparticles displayed maximum absorption at 260 nm in the UV-Vis spectrum. The distinct magnetite peak in the Fourier transform infrared (FTIR) spectroscopy spectra was observed at 574.75 cm-1. More research is needed into the intriguing prospect of biogenic magnetosome nanoparticles for antibacterial applications.
Asunto(s)
Antibacterianos , Magnetosomas , Nanopartículas , Providencia , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Hierro/química , Hierro/metabolismo , Klebsiella pneumoniae/efectos de los fármacos , Nanopartículas de Magnetita/química , Magnetosomas/química , Magnetosomas/metabolismo , Pruebas de Sensibilidad Microbiana , Nanopartículas/química , Tamaño de la Partícula , Providencia/química , Pseudomonas aeruginosa/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus/efectos de los fármacosRESUMEN
Magnetosomes are iron oxide or iron sulphide nano-sized particles surrounded by a lipid bilayer synthesised by a group of bacteria known as magnetotactic bacteria (MTB). Magnetosomes have become a promising candidate for biomedical applications and could be potentially used as a drug-carrier. However, pharmacokinetics and immunogenicity of the magnetosomes have not been understood yet which preclude its clinical applications. Herein, we investigated the pharmacokinetics of magnetosomes including Absorption, Distribution, Metabolism, and Elimination (ADME) along with its immunogenicity in vitro and in vivo. The magnetosomes were conjugated with fluorescein isothiocyanate (Mag-FITC) and their conjugation was confirmed through fluorescence microscopy and its absorption in HeLa cell lines was evaluated using flow cytometry analysis. The results revealed a maximum cell uptake of 97% at 200 µg/mL concentration. Further, the biodistribution of Mag-FITC was investigated in vivo by a bioimaging system using BALB/c mice as a subject at different time intervals. The Mag-FITC neither induced death nor physical distress and the same was eliminated post 36 h of injection with meagre intensities left behind. The metabolism and elimination analysis were assessed to detect the iron overload which revealed that magnetosomes were entirely metabolised within 48-h interval. Furthermore, the histopathology and serum analysis reveal no histological damage with the absence of any abnormal biochemical parameters. The results support our study that magnetosomes were completely removed from the blood circulation within 48-h time interval. Moreover, the immunogenicity analysis has shown that magnetosomes do not induce any inflammation as indicated by reduced peaks of immune markers such as IL 1ß, IL 2, IL 6, IL8, IFN γ, and TNF α estimated through Indirect ELISA. The normal behaviour of animals with the absence of acute or chronic toxicities in any organs declares that magnetosomes are safe to be injected. This shows that magnetosomes are benign for biological systems enrouting towards beneficial biomedical applications. Therefore, this study will advance the understanding and application of magnetosomes for clinical purposes.
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Magnetosomas , Humanos , Animales , Ratones , Magnetosomas/metabolismo , Células HeLa , Fluoresceína-5-Isotiocianato/metabolismo , Distribución Tisular , Bacterias/metabolismo , Óxido FerrosoférricoRESUMEN
Nitric oxide (NO) plays an essential role as signaling molecule in regulation of eukaryotic biomineralization, but its role in prokaryotic biomineralization is unknown. Magnetospirillum gryphiswaldense MSR-1, a model strain for studies of prokaryotic biomineralization, has the unique ability to form magnetosomes (magnetic organelles). We demonstrate here that magnetosome biomineralization in MSR-1 requires the presence of NsrRMg (an NO sensor) and a certain level of NO. MSR-1 synthesizes endogenous NO via nitrification-denitrification pathway to activate magnetosome formation. NsrRMg was identified as a global transcriptional regulator that acts as a direct activator of magnetosome gene cluster (MGC) and nitrification genes but as a repressor of denitrification genes. Specific levels of NO modulate DNA-binding ability of NsrRMg to various target promoters, leading to enhancing expression of MGC genes, derepressing denitrification genes, and repressing nitrification genes. These regulatory functions help maintain appropriate endogenous NO level. This study identifies for the first time the key transcriptional regulator of major MGC genes, clarifies the molecular mechanisms underlying NsrR-mediated NO signal transduction in magnetosome formation, and provides a basis for a proposed model of the role of NO in the evolutionary origin of prokaryotic biomineralization processes.
Asunto(s)
Proteínas Bacterianas , Magnetosomas , Magnetospirillum , Proteínas Bacterianas/metabolismo , Magnetosomas/genética , Magnetosomas/metabolismo , Magnetospirillum/genética , Magnetospirillum/metabolismo , Óxido Nítrico/metabolismo , Nitrógeno/metabolismoRESUMEN
In this study, two mutant strains, TBC and TBC+, able to biosynthesize a novel functional magnetosome-nanobody (Nb), were derived from the magnetotactic bacteria Magnetospirillum gryphiswaldense MSR-1. The magnetosome-Nbs biosynthesized by TBC+ containing multi-copies of the Nb gene had a higher binding ability to an environmental pollutant, tetrabromobisphenol A (TBBPA), than those biosynthesized by TBC containing only one copy of the Nb gene. The magnetosome-Nbs from TBC+ can effectively bind to TBBPA in solutions with high capacity without being affected by a broad range of NaCl and methanol concentrations as well as pH. Therefore, a magnetosome-Nb-based enzyme-linked immunosorbent assay (ELISA) was developed and optimized for the detection of TBBPA, yielding a half-maximum signal inhibition concentration of 0.23 ng/mL and a limit of detection of 0.025 ng/mL. The assay was used to detect TBBPA in spiked river water samples, giving average recoveries between 90 and 120% and coefficients of variation of 2.5-6.3%. The magnetosome-Nb complex could be reused 4 times in ELISA without affecting the performance of the assay. Our results demonstrate the potential of magnetosome-Nbs produced by TBC+ as cost-effective and environment-friendly reagents for immunoassays to detect small molecules in environmental waters.
Asunto(s)
Magnetosomas , Magnetosomas/metabolismo , Agua , Ensayo de Inmunoadsorción Enzimática , Proteínas Bacterianas/químicaRESUMEN
AIMS: Magnetotactic bacteria (MTB) can use their unique intracellular magnetosome organelles to swim along the Earth's magnetic field. They play important roles in the biogeochemical cycles of iron and sulfur. Previous studies have shown that the applied magnetic fields could affect the magnetosome formation and antioxidant defense systems in MTB. However, the molecular mechanisms by which magnetic fields affect MTB cells remain unclear. We aim to better understand the dark at 28°C-29°C for 20 h, as shownthe interactions between magnetic fields and cells, and the mechanism of MTB adaptation to magnetic field at molecular levels. METHODS AND RESULTS: We performed microbiological, transcriptomic, and genetic experiments to analyze the effects of a weak static magnetic field (SMF) exposure on the cell growth and magnetosome formation in the MTB strain Magnetospirillum magneticum AMB-1. The results showed that a 1.5 mT SMF significantly promoted the cell growth but reduced magnetosome formation in AMB-1, compared to the geomagnetic field. Transcriptomic analysis revealed decreased expression of genes primarily involved in the sulfate reduction pathway. Consistently, knockout mutant lacking adenylyl-sulfate kinase CysC did no more react to the SMF and the differences in growth and Cmag disappeared. Together with experimental findings of increased reactive oxidative species in the SMF-treated wild-type strain, we proposed that cysC, as a key gene, can participate in the cell growth and mineralization in AMB-1 by SMF regulation. CONCLUSIONS: This study suggests that the magnetic field exposure can trigger a bacterial oxidative stress response involved in AMB-1 growth and magnetosome mineralization by regulating the sulfur metabolism pathway. CysC may serve as a pivotal enzyme in mediating sulfur metabolism to synchronize the impact of SMF on both growth and magnetization of AMB-1.
Asunto(s)
Magnetosomas , Magnetosomas/genética , Magnetosomas/metabolismo , Sulfatos/metabolismo , Redes y Vías Metabólicas , Azufre/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
IMPORTANCE: To efficiently navigate within the geomagnetic field, magnetotactic bacteria (MTB) align their magnetosome organelles into chains, which are organized by the actin-like MamK protein. Although MamK is the most highly conserved magnetosome protein common to all MTB, its analysis has been confined to a small subgroup owing to the inaccessibility of most MTB. Our study takes advantage of a genetically tractable host where expression of diverse MamK orthologs together with a resurrected MamK LUCA and uncharacterized actin-like Mad28 proteins from deep-branching MTB resulted in gradual restoration of magnetosome chains in various mutants. Our results further indicate the existence of species-specific MamK interactors and shed light on the evolutionary relationships of one of the key proteins associated with bacterial magnetotaxis.
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Magnetosomas , Magnetospirillum , Actinas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Magnetospirillum/genética , Magnetospirillum/metabolismo , Magnetosomas/genética , Magnetosomas/metabolismo , Bacterias/metabolismoRESUMEN
For the potential in vitro/in vivo applications of magnetic iron oxide nanoparticles, their stability in different physiological fluids has to be ensured. This important prerequisite includes the preservation of the particles' stability during the envisaged application and, consequently, their invariance with respect to the transfer from storage conditions to cell culture media or even bodily fluids. Here, we investigate the colloidal stabilities of commercial nanoparticles with different coatings as a model system for biogenic iron oxide nanoparticles (magnetosomes) isolated from magnetotactic bacteria. We demonstrate that the stability can be evaluated and quantified by determining the intensity-weighted average of the particle sizes (Z-value) obtained from dynamic light scattering experiments as a simple quality criterion, which can also be used as an indicator for protein corona formation.
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Magnetosomas , Nanopartículas , Magnetosomas/metabolismo , Nanopartículas Magnéticas de Óxido de HierroRESUMEN
Bacterial magnetosomes synthesized by the magnetotactic bacterium Magnetospirillum magneticum are suitable for biomedical and biotechnological applications because of their high level of chemical purity of mineral with well-defined morphological features and a biocompatible lipid bilayer coating. However, utilizations of native magnetosomes are not sufficient for maximum effectiveness in many applications as the appropriate particle size differs. In this study, a method to control magnetosome particle size is developed for integration into targeted technological applications. The size and morphology of magnetosome crystals are highly regulated by the complex interactions of magnetosome synthesis-related genes; however, these interactions have not been fully elucidated. In contrast, previous studies have shown a positive correlation between vesicle and crystal sizes. Therefore, control of the magnetosome vesicle size is tuned by modifying the membrane lipid composition. Exogenous phospholipid synthesis pathways have been genetically introduced into M. magneticum. The experimental results show that these phospholipids altered the properties of the magnetosome membrane vesicles, which yielded larger magnetite crystal sizes. The genetic engineering approach presented in this study is shown to be useful for controlling magnetite crystal size without involving complex interactions of magnetosome synthesis-related genes.
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Nanopartículas de Magnetita , Magnetosomas , Magnetospirillum , Óxido Ferrosoférrico/química , Proteínas Bacterianas/metabolismo , Magnetosomas/genética , Magnetosomas/química , Magnetosomas/metabolismo , Magnetospirillum/genética , Magnetospirillum/metabolismo , Bacterias/metabolismo , Lípidos/análisisRESUMEN
Magnetotactic bacteria (MTB) are receiving attention for heavy metal biotreatment due to their potential for biosorption with heavy metals and the capability of the magnetic recovery. In this study, we investigated the characteristics of Cr(VI) bioreduction and biosorption by an MTB isolate, Magnetospirillum gryphiswaldense MSR-1, which has a higher growth rate and wider reflexivity in culture conditions. Our results demonstrated that the MSR-1 strain could remove Cr(VI) up to the concentration of 40 mg L-1 and with an optimal activity at neutral pH conditions. The magnetosome synthesis existed regulatory mechanisms between Cr(VI) reduction and cell division. The addition of 10 mg L-1 Cr(VI) significantly inhibited cell growth, but the magnetosome-deficient strain, B17316, showed an average specific growth rate of 0.062 h-1 at the same dosage. Cr(VI) reduction examined by the heat-inactivated and resting cells demonstrated that the main mechanism for MSR-1 strain to reduce Cr(VI) was chromate reductase and adsorption, and magnetosome synthesis would enhance the chromate reductase activity. Finally, our results elucidated that the chromate reductase distributes diversely in multiple subcellular components of the MSR-1 cells, including extracellular, membrane-associated, and intracellular cytoplasmic activity; and expression of the membrane-associated chromate reductase was increased after the cells were pre-exposed by Cr(VI).
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Magnetosomas , Magnetospirillum , Magnetosomas/metabolismo , Magnetosomas/ultraestructura , Cromatos/metabolismo , Magnetospirillum/metabolismo , Magnetospirillum/ultraestructuraRESUMEN
Magnetotactic bacteria (MTB) generate a membrane-enclosed subcellular compartment called magnetosome, which contains a biomineralized magnetite or greigite crystal, an inner membrane-derived lipid bilayer membrane, and a set of specifically targeted associated proteins. Magnetosomes are formed by a group of magnetosome-associated proteins encoded in a genomic region called magnetosome island. Magnetosomes are then arranged in a linear chain-like positioning, and the resulting magnetic dipole of the chain functions as a geomagnetic sensor for magneto-aerotaxis motility. Recent metagenomic analyses of environmental specimens shed light on the sizable phylogenetical diversity of uncultured MTB at the phylum level. These findings have led to a better understanding of the diversity and conservation of magnetosome-associated proteins. This review provides an overview of magnetosomes and magnetosome-associated proteins and introduces recent topics about this fascinating magnetic bacterial organelle.
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Magnetosomas , Magnetosomas/química , Magnetosomas/metabolismo , Magnetosomas/ultraestructura , Proteínas Bacterianas/metabolismo , Bacterias/genética , Óxido Ferrosoférrico/análisis , Óxido Ferrosoférrico/química , Óxido Ferrosoférrico/metabolismo , Bacterias GramnegativasRESUMEN
Magnetotactic bacteria (MTB), a diverse group of marine and freshwater microorganisms, have attracted the scientific community's attention since their discovery. These bacteria biomineralize ferrimagnetic nanocrystals, the magnetosomes, or biological magnetic nanoparticles (BMNs), in a single or multiple chain(s) within the cell. As a result, cells experience an optimized magnetic dipolar moment responsible for a passive alignment along the lines of the geomagnetic field. Advances in MTB cultivation and BMN isolation have contributed to the expansion of the biotechnological potential of MTB in recent decades. Several studies with mass-cultured MTB expanded the possibilities of using purified nanocrystals and whole cells in nano- and biotechnology. Freshwater MTB were primarily investigated in scaling up processes for the production of BMNs. However, marine MTB have the potential to overcome freshwater species applications due to the putative high efficiency of their BMNs in capturing molecules. Regarding the use of MTB or BMNs in different approaches, the application of BMNs in biomedicine remains the focus of most studies, but their application is not restricted to this field. In recent years, environment monitoring and recovery, engineering applications, wastewater treatment, and industrial processes have benefited from MTB-based biotechnologies. This review explores the advances in MTB large-scale cultivation and the consequent development of innovative tools or processes.
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Magnetosomas , Filogenia , Magnetosomas/química , Magnetosomas/metabolismo , Bacterias/metabolismo , Bacterias Gramnegativas , NanotecnologíaRESUMEN
Magnetotactic bacteria (MTB) are worth studying because of magnetosome biomineralization. Magnetosome biogenesis in MTB is controlled by multiple genes known as magnetosome-associated genes. Recent advances in bioinformatics provide a unique opportunity for studying functions of magnetosome-associated genes and networks that they are involved in. Furthermore, various types of bioinformatics analyses can also help identify genes associated with magnetosome biogenesis. To predict novel magnetosome-associated genes in the extended CtrA regulon, we analyzed expression data of Magnetospirillum magneticum AMB-1 in the GSE35625 dataset in NCBI GEO. We identified 10 potential magnetosome-associated genes using a combinational approach of differential expression analysis, Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis, protein-protein interaction network analysis and weighted gene co-expression network analysis. Meanwhile, we also discovered and compared two co-expression modules that most known magnetosome-associated genes belong to. Our comparison indicated the importance of energy on regulating co-expression module structures for magnetosome biogenesis. At the last stage of our research, we predicted at least four real magnetosome-associated genes out of 10 potential genes, based on a comparison of evolutionary trees between known and potential magnetosome-associated genes. Because of the discovery of common subtrees that the stressed species are enriched in, we proposed a hypothesis that multiple types of environmental stress can trigger magnetosome evolution in different waters, and therefore its evolution can recur at different times in various locations on earth. Overall, our research provides useful information for identifying new MTB species and understanding magnetosome biogenesis.
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Magnetosomas , Magnetospirillum , Magnetosomas/genética , Magnetosomas/metabolismo , Regulón/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Magnetospirillum/genética , Magnetospirillum/metabolismo , Penicilinas/metabolismoRESUMEN
BACKGROUND: One of the most complex prokaryotic organelles are magnetosomes, which are formed by magnetotactic bacteria as sensors for navigation in the Earth's magnetic field. In the alphaproteobacterium Magnetospirillum gryphiswaldense magnetosomes consist of chains of magnetite crystals (Fe3O4) that under microoxic to anoxic conditions are biomineralized within membrane vesicles. To form such an intricate structure, the transcription of > 30 specific structural genes clustered within the genomic magnetosome island (MAI) has to be coordinated with the expression of an as-yet unknown number of auxiliary genes encoding several generic metabolic functions. However, their global regulation and transcriptional organization in response to anoxic conditions most favorable for magnetite biomineralization are still unclear. RESULTS: Here, we compared transcriptional profiles of anaerobically grown magnetosome forming cells with those in which magnetosome biosynthesis has been suppressed by aerobic condition. Using whole transcriptome shotgun sequencing, we found that transcription of about 300 of the > 4300 genes was significantly enhanced during magnetosome formation. About 40 of the top upregulated genes are directly or indirectly linked to aerobic and anaerobic respiration (denitrification) or unknown functions. The mam and mms gene clusters, specifically controlling magnetosome biosynthesis, were highly transcribed, but constitutively expressed irrespective of the growth condition. By Cappable-sequencing, we show that the transcriptional complexity of both the MAI and the entire genome decreased under anaerobic conditions optimal for magnetosome formation. In addition, predominant promoter structures were highly similar to sigma factor σ70 dependent promoters in other Alphaproteobacteria. CONCLUSIONS: Our transcriptome-wide analysis revealed that magnetite biomineralization relies on a complex interplay between generic metabolic processes such as aerobic and anaerobic respiration, cellular redox control, and the biosynthesis of specific magnetosome structures. In addition, we provide insights into global regulatory features that have remained uncharacterized in the widely studied model organism M. gryphiswaldense, including a comprehensive dataset of newly annotated transcription start sites and genome-wide operon detection as a community resource (GEO Series accession number GSE197098).
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Magnetosomas , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biomineralización/genética , Óxido Ferrosoférrico/análisis , Óxido Ferrosoférrico/metabolismo , Magnetosomas/genética , Magnetosomas/metabolismo , Magnetospirillum , Factor sigma/genética , TranscriptomaRESUMEN
Since magnetic micro/nano-materials can serve as multifunctional transducers for remote control of cell functions by applying diverse magnetic fields, magnetic cell manipulation provides a highly promising tool in biomedical research encompassing neuromodulation, tissue regeneration engineering and tumor cell destruction. Magnetotactic bacteria (MTB), which contain natural magnetic materials, can sensitively respond to external magnetic fields via their endogenous magnetosome chains. Here, we developed a technique for magnetotactic bacteria-based cell modulation and tumor suppression combined with a swing magnetic field. We enabled MTB cells to recognize and bind to mammalian tumor cells via functional modification with RGD peptides onto the surfaces of MTB cells, and RGD-modified MTB bacteria could interact with the targeted tumor cells effectively. The magnetic torque, which was due to the interaction of the long magnetosome chain inside the MTB bacterial cell and the applied swing magnetic field, could result in obvious swing magnetic behaviors of the modified MTB bacteria bound to tumor cell surfaces and thus subsequently exert a sustained magnetomechanical oscillation on the tumor cell surfaces, which could induce a significant activation of Ca2+ ion influx in vitro and tumor growth inhibition in vivo. These findings suggest that MTB cells mediated magnetomechanical stimulation, which is remotely controlled by dynamic magnetic fields, as an effective way to regulate cell signaling and treat tumor growth, which will shed the light on further biomedical applications utilizing whole magnetotactic bacteria.
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Magnetosomas , Animales , Magnetosomas/metabolismo , Bacterias Gramnegativas , Bacterias/metabolismo , Magnetismo , MamíferosRESUMEN
Magnetosomes of magnetotactic bacteria consist of magnetic nanocrystals with defined morphologies enclosed in vesicles originated from cytoplasmic membrane invaginations. Although many proteins are involved in creating magnetosomes, a single magnetosome protein, Mms6 from Magnetospirillum magneticum strain AMB-1, can direct the crystallization of magnetite nanoparticles in vitro. The in vivo role of Mms6 in magnetosome formation is debated, and the observation that Mms6 binds Fe3+ more tightly than Fe2+ raises the question of how, in a magnetosome environment dominated by Fe3+, Mms6 promotes the crystallization of magnetite, which contains both Fe3+ and Fe2+. Here we show that Mms6 is a ferric reductase that reduces Fe3+ to Fe2+ using NADH and FAD as electron donor and cofactor, respectively. Reductase activity is elevated when Mms6 is integrated into either liposomes or bicelles. Analysis of Mms6 mutants suggests that the C-terminal domain binds iron and the N-terminal domain contains the catalytic site. Although Mms6 forms multimers that involve C-terminal and N-terminal domain interactions, a fusion protein with ubiquitin remains a monomer and displays reductase activity, which suggests that the catalytic site is fully in the monomer. However, the quaternary structure of Mms6 appears to alter the iron binding characteristics of the C-terminal domain. These results are consistent with a hypothesis that Mms6, a membrane protein, promotes the formation of magnetite in vivo by a mechanism that involves reducing iron.
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Magnetosomas , Magnetospirillum , Proteínas Bacterianas/química , FMN Reductasa/metabolismo , Óxido Ferrosoférrico/metabolismo , Flavina-Adenina Dinucleótido/metabolismo , Hierro/metabolismo , Lípidos/análisis , Liposomas/metabolismo , Magnetosomas/metabolismo , Magnetospirillum/metabolismo , Proteínas de la Membrana/metabolismo , NAD/metabolismo , Ubiquitinas/metabolismoRESUMEN
Metal sulfides are a common group of extracellular bacterial biominerals. However, only a few cases of intracellular biomineralization are reported in this group, mostly limited to greigite (Fe3 S4 ) in magnetotactic bacteria. Here, a previously unknown periplasmic biomineralization of copper sulfide produced by the magnetotactic bacterium Desulfamplus magnetovallimortis strain BW-1, a species known to mineralize greigite (Fe3 S4 ) and magnetite (Fe3 O4 ) in the cytoplasm is reported. BW-1 produces hundreds of spherical nanoparticles, composed of 1-2 nm substructures of a poorly crystalline hexagonal copper sulfide structure that remains in a thermodynamically unstable state. The particles appear to be surrounded by an organic matrix as found from staining and electron microscopy inspection. Differential proteomics suggests that periplasmic proteins, such as a DegP-like protein and a heavy metal-binding protein, could be involved in this biomineralization process. The unexpected periplasmic formation of copper sulfide nanoparticles in BW-1 reveals previously unknown possibilities for intracellular biomineralization that involves intriguing biological control and holds promise for biological metal recovery in times of copper shortage.