Publications by authors named "Dinka Mandakovic"

15 Publications

  • Page 1 of 1

Tomato Cultivars With Variable Tolerances to Water Deficit Differentially Modulate the Composition and Interaction Patterns of Their Rhizosphere Microbial Communities.

Front Plant Sci 2021 13;12:688533. Epub 2021 Jul 13.

Laboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile.

Since drought is the leading environmental factor limiting crop productivity, and plants have a significant impact in defining the assembly of plant-specific microbial communities associated with roots, we aimed to determine the effect of thoroughly selected water deficit tolerant and susceptible cultivars on their rhizosphere microbiome and compared their response with plant-free soil microbial communities. We identified a total of 4,248 bacterial and 276 fungal different operational taxonomic units (OTUs) in soils by massive sequencing. We observed that tomato cultivars significantly affected the alpha and beta diversity of their bacterial rhizosphere communities but not their fungal communities compared with bulk soils (BSs), showing a plant effect exclusively on the bacterial soil community. Also, an increase in alpha diversity in response to water deficit of both bacteria and fungi was observed in the susceptible rhizosphere (SRz) but not in the tolerant rhizosphere (TRz) cultivar, implying a buffering effect of the tolerant cultivar on its rhizosphere microbial communities. Even though water deficit did not affect the microbial diversity of the tolerant cultivar, the interaction network analysis revealed that the TRz microbiota displayed the smallest and least complex soil network in response to water deficit with the least number of connected components, nodes, and edges. This reduction of the TRz network also correlated with a more efficient community, reflected in increased cooperation within kingdoms. Furthermore, we identified some specific bacteria and fungi in the TRz in response to water deficit, which, given that they belong to taxa with known beneficial characteristics for plants, could be contributing to the tolerant phenotype, highlighting the metabolic bidirectionality of the holobiont system. Future assays involving characterization of root exudates and exchange of rhizospheres between drought-tolerant and susceptible cultivars could determine the effect of specific metabolites on the microbiome community and may elucidate their functional contribution to the tolerance of plants to water deficit.
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http://dx.doi.org/10.3389/fpls.2021.688533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313812PMC
July 2021

Increased dietary availability of selenium in rainbow trout (Oncorhynchus mykiss) improves its plasma antioxidant capacity and resistance to infection with Piscirickettsia salmonis.

Vet Res 2021 May 1;52(1):64. Epub 2021 May 1.

Laboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de Chile, El Líbano, Macul, 5524, Santiago, Chile.

Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is the most important infectious disease in the Chilean salmon farming industry. An opportunity to control this disease is to use functional micronutrients to modulate host mechanisms of response to the infection. Since P. salmonis may affect the host antioxidant system in salmonids, particularly that dependent on selenium (Se), we hypothesized that fish's dietary selenium supplementation could improve the response to the bacterial infection. To address this, we defined a non-antibiotic, non-cytotoxic concentration of selenium to evaluate its effect on the response to in vitro infections of SHK-1 cells with P. salmonis. The results indicated that selenium supplementation reduced the cytopathic effect, intracellular bacterial load, and cellular mortality of SHK-1 by increasing the abundance and activity of host glutathione peroxidase. We then prepared diets supplemented with selenium up to 1, 5, and 10 mg/kg to feed juvenile trout for 8 weeks. At the end of this feeding period, we obtained their blood plasma and evaluated its ability to protect SHK-1 cells from infection with P. salmonis in ex vivo assays. These results recapitulated the observed ability of selenium to protect against infection with P. salmonis by increasing the concentration of selenium and the antioxidant capacity in fish's plasma. To the best of our knowledge, this is the first report of the protective capacity of selenium against P. salmonis infection in salmonids, becoming a potential effective host-directed dietary therapy for SRS and other infectious diseases in animals at a non-antibiotic concentration.
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http://dx.doi.org/10.1186/s13567-021-00930-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088010PMC
May 2021

Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection.

Vet Res 2020 Oct 28;51(1):134. Epub 2020 Oct 28.

Laboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de Chile, Av. El Líbano 5524, Macul, 7830490, Santiago, Chile.

Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens.
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http://dx.doi.org/10.1186/s13567-020-00845-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592559PMC
October 2020

Isolation and Identification of Soil Bacteria from Extreme Environments of Chile and Their Plant Beneficial Characteristics.

Microorganisms 2020 Aug 10;8(8). Epub 2020 Aug 10.

Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, El Libano 5524, 7810000 Santiago, Chile.

The isolation of soil bacteria from extreme environments represents a major challenge, but also an opportunity to characterize the metabolic potential of soil bacteria that could promote the growth of plants inhabiting these harsh conditions. The aim of this study was to isolate and identify bacteria from two Chilean desert environments and characterize the beneficial traits for plants through a biochemical approach. By means of different culture strategies, we obtained 39 bacterial soil isolates from the Coppermine Peninsula (Antarctica) and 32 from Lejía Lake shore soil (Atacama Desert). The results obtained from the taxonomic classification and phylogenetic analysis based on 16S rDNA sequences indicated that the isolates belonged to four phyla (Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes), and that the most represented genus at both sites was . Regarding biochemical characterization, all strains displayed in vitro PGP capabilities, but these were in different proportions that grouped them according to their site of origin. This study contributes with microbial isolates from natural extreme environments with biotechnological potentials in improving plant growth under cold stress.
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http://dx.doi.org/10.3390/microorganisms8081213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466141PMC
August 2020

Fungal Diversity Analysis of Grape Musts from Central Valley-Chile and Characterization of Potential New Starter Cultures.

Microorganisms 2020 Jun 24;8(6). Epub 2020 Jun 24.

Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago 7810000, Chile.

Autochthonous microorganisms are an important source of the distinctive metabolites that influence the chemical profile of wine. However, little is known about the diversity of fungal communities associated with grape musts, even though they are the source of local yeast strains with potential capacities to become starters during fermentation. By using internal transcribed spacer (ITS) amplicon sequencing, we identified the taxonomic structure of the yeast community in unfermented and fermented musts of a typical L. var. Sauvignon blanc from the Central Valley of Chile throughout two consecutive seasons of production. Unsurprisingly, represented the most abundant fungal genus in unfermented and fermented musts, mainly due to the contribution of (42.7%) and (80%). Unfermented musts were highly variable between seasons and showed higher values of fungal diversity than fermented musts. Since microbial physiological characterization is primarily achieved in culture, we isolated nine species belonging to six genera of fungi from the unfermented must samples. All isolates were characterized for their potential capacities to be used as new starters in wine. Remarkably, only could co-exist with a commercial strain under fermentative conditions, representing a feasible candidate strain for wine production.
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http://dx.doi.org/10.3390/microorganisms8060956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356840PMC
June 2020

Genome-scale metabolic models of Microbacterium species isolated from a high altitude desert environment.

Sci Rep 2020 03 27;10(1):5560. Epub 2020 Mar 27.

Laboratorio de Bioinformática y Expresión Génica, INTA-Universidad de Chile, El Líbano, 5524, Santiago, Chile.

The Atacama Desert is the most arid desert on Earth, focus of important research activities related to microbial biodiversity studies. In this context, metabolic characterization of arid soil bacteria is crucial to understand their survival strategies under extreme environmental stress. We investigated whether strain-specific features of two Microbacterium species were involved in the metabolic ability to tolerate/adapt to local variations within an extreme desert environment. Using an integrative systems biology approach we have carried out construction and comparison of genome-scale metabolic models (GEMs) of two Microbacterium sp., CGR1 and CGR2, previously isolated from physicochemically contrasting soil sites in the Atacama Desert. Despite CGR1 and CGR2 belong to different phylogenetic clades, metabolic pathways and attributes are highly conserved in both strains. However, comparison of the GEMs showed significant differences in the connectivity of specific metabolites related to pH tolerance and CO production. The latter is most likely required to handle acidic stress through decarboxylation reactions. We observed greater GEM connectivity within Microbacterium sp. CGR1 compared to CGR2, which is correlated with the capacity of CGR1 to tolerate a wider pH tolerance range. Both metabolic models predict the synthesis of pigment metabolites (β-carotene), observation validated by HPLC experiments. Our study provides a valuable resource to further investigate global metabolic adaptations of bacterial species to grow in soils with different abiotic factors within an extreme environment.
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http://dx.doi.org/10.1038/s41598-020-62130-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101325PMC
March 2020

Soil Bacterial Communities From the Chilean Andean Highlands: Taxonomic Composition and Culturability.

Front Bioeng Biotechnol 2019 5;7:10. Epub 2019 Feb 5.

Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile.

The Atacama Desert is a highly complex, extreme ecosystem which harbors microorganisms remarkable for their biotechnological potential. Here, a soil bacterial prospection was carried out in the high Altiplano region of the Atacama Desert (>3,800 m above sea level; m a.s.l.), where direct anthropogenic interference is minimal. We studied: (1) soil bacterial community composition using high-throughput sequencing of the 16S rRNA gene and (2) bacterial culturability, by using a soil extract medium (SEM) under a factorial design of three factors: temperature (15 and 30°C), nutrient content (high and low nutrient disposal) and oxygen availability (presence and absence). A total of 4,775 OTUs were identified and a total of 101 isolates were selected for 16S rRNA sequencing, 82 of them corresponded to unique or non-redundant sequences. To expand our view of the Altiplano landscape and to obtain a better representation of its microbiome, we complemented our Operational Taxonomic Units (OTUs) and isolate collection with data from other previous data from our group and obtained a merged set of OTUs and isolates that we used to perform our study. Taxonomic comparisons between culturable microbiota and metabarcoding data showed an overrepresentation of the phylum Firmicutes (44% of isolates vs. 2% of OTUs) and an underrepresentation of Proteobacteria (8% of isolates vs. 36% of OTUs). Within the Next Generation Sequencing (NGS) results, 33% of the OTUs were unknown up to genus, revealing an important proportion of putative new species in this environment. Biochemical characterization and analysis extracted from the literature indicated that an important number of our isolates had biotechnological potential. Also, by comparing our results with similar studies on other deserts, the Altiplano highland was most similar to a cold arid desert. In summary, our study contributes to expand the knowledge of soil bacterial communities in the Atacama Desert and complements the pipeline to isolate selective bacteria that could represent new potential biotechnological resources.
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http://dx.doi.org/10.3389/fbioe.2019.00010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371850PMC
February 2019

Bacterial communities associated to Chilean altiplanic native plants from the Andean grasslands soils.

Sci Rep 2019 01 31;9(1):1042. Epub 2019 Jan 31.

FONDAP Center for Genome Regulation, Santiago, Chile.

The rhizosphere is considered the primary place for soil microbiome differentiation and plays a key role in plant survival, especially for those subjected to environmental stress. Using high-throughput sequencing of the 16S rRNA gene, we analyzed and compared soil bacterial communities associated to four of the most abundant high altitude native plant species of the Chilean Andean grasslands. We examined three soil compartments: the rhizosphere (bacteria firmly attached to the roots), the rhizosphere-surrounding soil (bacteria loosely attached to the roots) and the bulk soil (plant-free soil). The rhizosphere microbiome was in all cases the least diverse, exposing that the bulk soil was a more complex environment. Taxonomic analysis revealed an abrupt change between the rhizosphere and the rest of the non-rhizospheric soils. Thus, while rhizobacterial communities were enriched in Proteobacteria (mainly Alphaproteobacteria), Actinobacteria (mostly Blastocatellia) dominated in bulk soils. Finally, we detected certain taxonomic rhizosphere signatures, which could be attributed to a particular genotype. Overall, our results indicate that the thin layer of soil surrounding the roots constitute a distinctive soil environment. This study contributes to expand the knowledge about soil bacterial communities in the Chilean highlands and takes the first step to understand the processes that might lead to the rhizosphere differentiation in that area.
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http://dx.doi.org/10.1038/s41598-018-37776-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355873PMC
January 2019

Microbiome analysis and bacterial isolation from Lejía Lake soil in Atacama Desert.

Extremophiles 2018 Jul 23;22(4):665-673. Epub 2018 Apr 23.

Laboratorio de Bioinformática y Expresión Génica, INTA-Universidad de Chile, El Líbano, 5524, Santiago, Chile.

As a consequence of the severe climatic change affecting our entire world, many lakes in the Andes Cordillera are likely to disappear within a few decades. One of these lakes is Lejía Lake, located in the central Atacama Desert. The objectives of this study were: (1) to characterize the bacterial community from Lejía Lake shore soil (LLS) using 16S rRNA sequencing and (2) to test a culture-based approach using a soil extract medium (SEM) to recover soil bacteria. This extreme ecosystem was dominated by three phyla: Bacteroidetes, Proteobacteria, and Firmicutes with 29.2, 28.2 and 28.1% of the relative abundance, respectively. Using SEM, we recovered 7.4% of the operational taxonomic units from LLS, all of which belonged to the same three dominant phyla from LLS (6.9% of Bacteroidetes, 77.6% of Proteobacteria, and 15.3% of Firmicutes). In addition, we used SEM to recover isolates from LLS and supplemented the culture medium with increasing salt concentrations to isolate microbial representatives of salt tolerance (Halomonas spp.). The results of this study complement the list of microbial taxa diversity from the Atacama Desert and assess a pipeline to isolate selective bacteria that could represent useful elements for biotechnological approaches.
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http://dx.doi.org/10.1007/s00792-018-1027-6DOI Listing
July 2018

Structure and co-occurrence patterns in microbial communities under acute environmental stress reveal ecological factors fostering resilience.

Sci Rep 2018 04 12;8(1):5875. Epub 2018 Apr 12.

Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile.

Understanding the factors that modulate bacterial community assembly in natural soils is a longstanding challenge in microbial community ecology. In this work, we compared two microbial co-occurrence networks representing bacterial soil communities from two different sections of a pH, temperature and humidity gradient occurring along a western slope of the Andes in the Atacama Desert. In doing so, a topological graph alignment of co-occurrence networks was used to determine the impact of a shift in environmental variables on OTUs taxonomic composition and their relationships. We observed that a fraction of association patterns identified in the co-occurrence networks are persistent despite large environmental variation. This apparent resilience seems to be due to: (1) a proportion of OTUs that persist across the gradient and maintain similar association patterns within the community and (2) bacterial community ecological rearrangements, where an important fraction of the OTUs come to fill the ecological roles of other OTUs in the other network. Actually, potential functional features suggest a fundamental role of persistent OTUs along the soil gradient involving nitrogen fixation. Our results allow identifying factors that induce changes in microbial assemblage configuration, altering specific bacterial soil functions and interactions within the microbial communities in natural environments.
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http://dx.doi.org/10.1038/s41598-018-23931-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897386PMC
April 2018

Genomic-Based Restriction Enzyme Selection for Specific Detection of Piscirickettsia salmonis by 16S rDNA PCR-RFLP.

Front Microbiol 2016 9;7:643. Epub 2016 May 9.

Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de ChileSantiago, Chile; Fondap Center for Genoma RegulationSantiago, Chile; Laboratorio de Genómica Aplicada, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de ChileSantiago, Chile.

The gram negative facultative bacterium P. salmonis is the etiological agent of Salmonid Rickettsial Septicaemia (SRS), a severe disease that causes important economic losses in the global salmon farmer industry. Despite efforts to control this disease, the high frequency of new epizootic events indicate that the vaccine and antibiotics treatments have limited effectiveness, therefore the preventive and diagnostic approaches must be improved. A comparison of several methodologies for SRS diagnostic indicate differences in their specificity and its capacity to detect other bacteria coexisting with P. salmonis in culture media (contamination) and fish samples (coinfection), aspects relevant for research, vaccine development and clinical diagnostic. By computer-simulation analyses, we identified a group of restriction enzymes that generate unique P. salmonis 16S rDNA band patterns, distinguishable from all other bacteria. From this information, we designed and developed a PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) assay, which was validated using 16S rDNA universal primers and restriction enzyme PmaCI for the amplification and digestion, respectively. Experimental validation was performed by comparing the restriction pattern of P. salmonis with the restriction patterns generated by bacteria that cohabit with P. salmonis (fish bacterial isolates and culture media contaminants). Our results indicate that the restriction enzyme selection pipeline was suitable to design a more specific, sensible, faster and cheaper assay than the currently used P. salmonis detection methodologies.
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http://dx.doi.org/10.3389/fmicb.2016.00643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860512PMC
May 2016

CyDiv, a Conserved and Novel Filamentous Cyanobacterial Cell Division Protein Involved in Septum Localization.

Front Microbiol 2016 10;7:94. Epub 2016 Feb 10.

Laboratorio de Ecología Microbiana y Toxicología Ambiental, Department of Molecular Genetics and Microbiology, Pontificia Universidad Católica de Chile Santiago, Chile.

Cell division in bacteria has been studied mostly in Escherichia coli and Bacillus subtilis, model organisms for Gram-negative and Gram-positive bacteria, respectively. However, cell division in filamentous cyanobacteria is poorly understood. Here, we identified a novel protein, named CyDiv (Cyanobacterial Division), encoded by the all2320 gene in Anabaena sp. PCC 7120. We show that CyDiv plays a key role during cell division. CyDiv has been previously described only as an exclusive and conserved hypothetical protein in filamentous cyanobacteria. Using polyclonal antibodies against CyDiv, we showed that it localizes at different positions depending on cell division timing: poles, septum, in both daughter cells, but also in only one of the daughter cells. The partial deletion of CyDiv gene generates partial defects in cell division, including severe membrane instability and anomalous septum localization during late division. The inability to complete knock out CyDiv strains suggests that it is an essential gene. In silico structural protein analyses and our experimental results suggest that CyDiv is an FtsB/DivIC-like protein, and could therefore, be part of an essential late divisome complex in Anabaena sp. PCC 7120.
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http://dx.doi.org/10.3389/fmicb.2016.00094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748335PMC
February 2016

Complete genome sequence of Microbacterium sp. CGR1, bacterium tolerant to wide abiotic conditions isolated from the Atacama Desert.

J Biotechnol 2015 Dec 29;216:149-50. Epub 2015 Oct 29.

Laboratorio de Bioinformática y Expresión Génica, INTA-Universidad de Chile, El Líbano 5524 Santiago, Chile; Fondap Center for Genome Regulation (CGR), Avenida Blanco Encalada 2085 Santiago, Chile. Electronic address:

Microbacterium sp. CGR1 (RGM2230) is an isolate from the Atacama Desert that displays a wide pH, salinity and temperature tolerance. This strain exhibits riboflavin overproducer features and traits for developing an environmental arsenic biosensor. Here, we report the complete genome sequence of this strain, which represents the first genome of the genus Microbacterium sequenced and assembled in a single contig. The genome contains 3,634,864bp, 3299 protein-coding genes, 45 tRNAs, six copies of 5S-16S-23S rRNA and a high genome average GC-content of 68.04%.
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http://dx.doi.org/10.1016/j.jbiotec.2015.10.020DOI Listing
December 2015

Intercellular transfer along the trichomes of the invasive terminal heterocyst forming cyanobacterium Cylindrospermopsis raciborskii CS-505.

FEMS Microbiol Lett 2015 Mar 4;362(5). Epub 2014 Dec 4.

Department of Molecular Genetics and Microbiology, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago 8331150, Chile

Cylindrospermopsis raciborskii CS-505 is an invasive freshwater filamentous cyanobacterium that when grown diazotrophically may develop trichomes of up to 100 vegetative cells while differentiating only two end heterocysts, the sole sites for their N2-fixation process. We examined the diazotrophic growth and intercellular transfer mechanisms in C. raciborskii CS-505. Subjecting cultures to a combined-nitrogen-free medium to elicit N2 fixation, the trichome length remained unaffected while growth rates decreased. The structures and proteins for intercellular communication showed that while a continuous periplasmic space was apparent along the trichomes, the putative septal junction sepJ gene is divided into two open reading frames and lacks several transmembrane domains unlike the situation in Anabaena, differentiating a 5-fold higher frequency of heterocysts. FRAP analyses also showed that the dyes calcein and 5-CFDA were taken up by heterocysts and vegetative cells, and that the transfer from heterocysts and 'terminal' vegetative cells showed considerably higher transfer rates than that from vegetative cells located in the middle of the trichomes. The data suggest that C. raciborskii CS-505 compensates its low-frequency heterocyst phenotype by a highly efficient transfer of the fixed nitrogen towards cells in distal parts of the trichomes (growing rapidly) while cells in central parts suffers (slow growth).
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http://dx.doi.org/10.1093/femsle/fnu009DOI Listing
March 2015

Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells.

J Immunol 2007 Jun;178(11):6949-57

Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

Previously, we found that human dendritic cells (hDCs) pulsed with a melanoma cell lysate (MCL) and stimulated with TNF-alpha (MCL/TNF) acquire a mature phenotype in vitro and are able to trigger tumor-specific immune responses when they are used in melanoma immunotherapy in patients. In this study, we describe that MCL/TNF induces gap junction (GJ)-mediated intercellular communications and promotes melanoma Ag transfer between ex vivo produced hDCs from melanoma patients. hDCs also exhibit increased expression of the GJ-related protein connexin 43, which contributes to GJ plaque formation after MCL/TNF stimulation. The addition of GJ inhibitors suppresses intercellular tumor Ag transfer between hDCs, thus reducing melanoma-specific T cell activation. In summary, we demonstrate that MCL/TNF-stimulated hDCs can establish functional GJ channels that participate in melanoma Ag transfer, facilitating Ag cross-presentation and an effective dendritic cell-mediated melanoma-specific T cell response. These results suggest that GJs formed between hDCs used in cancer vaccination protocols could be essentials for the establishment of a more efficient antitumor response.
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http://dx.doi.org/10.4049/jimmunol.178.11.6949DOI Listing
June 2007
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