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1.
Curr Biol ; 32(9): 1961-1973.e4, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35349792

RESUMO

Multicellularity evolved in fungi and animals, or the opisthokonts, from their common amoeboflagellate ancestor but resulted in strikingly distinct cellular organizations. The origins of this multicellularity divergence are not known. The stark mechanistic differences that underlie the two groups and the lack of information about ancestral cellular organizations limits progress in this field. We discovered a new type of invasive multicellular behavior in Fonticula alba, a unique species in the opisthokont tree, which has a simple, bacteria-feeding sorocarpic amoeba lifestyle. This invasive multicellularity follows germination dependent on the bacterial culture state, after which amoebae coalesce to form dynamic collectives that invade virgin bacterial resources. This bacteria-dependent social behavior emerges from amoeba density and allows for rapid and directed invasion. The motile collectives have animal-like properties but also hyphal-like search and invasive behavior. These surprising findings enrich the diverse multicellularities present within the opisthokont lineage and offer a new perspective on fungal origins.


Assuntos
Dictyosteliida , Animais , Bactérias , Eucariotos , Fungos , Filogenia
2.
Philos Trans R Soc Lond B Biol Sci ; 376(1820): 20190756, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33487113

RESUMO

Dictyostelid social amoebas respond to starvation by self-organizing into multicellular slugs that migrate towards light to construct spore-bearing structures. These behaviours depend on excitable networks that enable amoebas to produce propagating waves of the chemoattractant cAMP, and to respond by directional movement. cAMP additionally regulates cell differentiation throughout development, with differentiation and cell movement being coordinated by interaction of the stalk inducer c-di-GMP with the adenylate cyclase that generates cAMP oscillations. Evolutionary studies indicate how the manifold roles of cAMP in multicellular development evolved from a role as intermediate for starvation-induced encystation in the unicellular ancestor. A merger of this stress response with the chemotaxis excitable networks yielded the developmental complexity and cognitive capabilities of extant Dictyostelia. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.


Assuntos
Evolução Biológica , Cognição , Dictyosteliida/fisiologia , Percepção de Quorum , Transdução de Sinais
3.
Protist ; 171(5): 125756, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33126017

RESUMO

Dictyostelid cellular slime molds (dictyostelids) are important soil microorganisms that feed mostly on bacteria in the soil and leaf litter layer. The Russian Far East is the easternmost part of Russia and thus is located in the Middle East of Siberia. In September 2018, 14 samples of mixed soil/humus were collected from the most southeastern portion of the Russian Far East, including Sakhalin Island, Ussuriysk and Vladivostok, and then processed for dictyostelids. Seven species in four genera were recovered. Four of these species (Cavenderia fasciculata, Heterostelium tenuissimum, Dictyostelium longosporum and Polysphondylium patagonicum) were recorded for the first time from Russia, and one species (H. multibrachiatum sp. nov.) in described herein as new to science.


Assuntos
Dictyosteliida/classificação , Solo/parasitologia , Dictyosteliida/genética , Filogenia , RNA Ribossômico 18S/genética , Federação Russa , Especificidade da Espécie
4.
Mycologia ; 112(5): 1026-1042, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33006910

RESUMO

Dictyostelids are a monophyletic group of sorocarp-forming social amoebae in the major eukaryotic division Amoebozoa. Members of this taxon, which is made up of almost 200 described species, are common in terrestrial soils globally. Still, the alpha diversity is not well known in many areas, and new species are frequently recovered. The highest species richness is found in the tropics. Here, five new species are described from soil samples collected in Madagascar. These species-Cavenderia basinodulosa, C. canoespora, Heterostelium radiatum, H. versatile, and Raperostelium stabile-are described based on both morphological characteristics and molecular data, with sequence data from the rDNA small subunit (SSU). The five new species are morphologically disparate, ranging from relatively small, robust taxa such as R. stabile to taxa with variable morphologies such as the larger H. radiatum and H. versatile and the yellow-tinted and irregularly branched species C. canoespora and C. basinulosa. These new species, together with earlier work where 13 other species were described from the island, suggest that there is a range of genetically diverse and highly morphologically variable dictyostelid taxa occurring on Madagascar, suggesting biogeographic patterns even within these very small organisms.


Assuntos
Biodiversidade , Dictyosteliida/classificação , Dictyosteliida/genética , Filogenia , Microbiologia do Solo , DNA Ribossômico/genética , Variação Genética , Madagáscar
5.
J Exp Zool B Mol Dev Evol ; 332(8): 365-370, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31742864

RESUMO

Throughout his life, John Tyler Bonner contributed to major transformations in the fields of developmental and evolutionary biology. He pondered the evolution of complexity and the significance of randomness in evolution, and was instrumental in the formation of evolutionary developmental biology. His contributions were vast, ranging from highly technical scientific articles to numerous books written for a broad audience. This historical vignette gathers reflections by several prominent researchers on the greatness of John Bonner and the implications of his work.


Assuntos
Evolução Biológica , Biologia do Desenvolvimento , Dictyosteliida , História do Século XX , História do Século XXI
6.
J Exp Zool B Mol Dev Evol ; 332(8): 331-338, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31380606

RESUMO

John Bonner presented a provocative conjecture that the means by which organisms evolve has itself evolved. The elements of his postulated nonuniformitarianism in the essay under discussion-the emergence of sex, the enhanced selection pressures on larger multicellular forms-center on a presumed close mapping of genotypic to phenotypic change. A different view emerges from delving into earlier work of Bonner's in which he proposed the concept of "neutral phenotypes" and "neutral morphologies" allied to D'Arcy Thompson's analysis of physical determinants of form and studied the conditional elicitation of intrinsic organizational properties of cell aggregates in social amoebae. By comparing the shared and disparate mechanistic bases of morphogenesis and developmental outcomes in the embryos of metazoans (animals), closely related nonmetazoan holozoans, more distantly related dictyostelids, and very distantly related volvocine algae, I conclude, in agreement with Bonner's earlier proposals, that understanding the evolution of multicellular evolution requires knowledge of the inherent forms of diversifying lineages, and that the relevant causative factors extend beyond genes and adaptation to the physics of materials.


Assuntos
Evolução Biológica , Animais , Clorófitas , Biologia do Desenvolvimento , Dictyosteliida , Morfogênese
7.
mSphere ; 4(2)2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971444

RESUMO

Christmas Island (10°30'S, 105°40'E) is an Australian external territory located in the Indian Ocean, approximately 350 km south of Java and Sumatra and about 1,550 km northwest of the closest point on the Australian mainland. In May 2017, 20 samples of soil/humus were collected on Christmas Island and processed for dictyostelid cellular slime molds. Four species were recovered. Two of these (Dictyostelium purpureum and Cavenderia aureostipes) are common and widely distributed throughout the world, but two other species (Dictyostelium insulinativitatis sp. nov. and Dictyostelium barbarae sp. nov.) were found to be new to science and are described here.IMPORTANCE Reported here are the results of a study for dictyostelids carried out on Christmas Island, Indian Ocean. Six isolates representing four species of dictyostelid cellular slime molds were obtained from two of the four localities from which samples were collected on the island. Two of the species (Dictyostelium insulinativitatis and D. barbarae) belong to the Dictyosteliaceae, genus Dictyostelium, and are new to science. These are described based on both morphology and phylogeny. The diversity and abundance of dictyostelids on Christmas Island appear to be low, which might in part be due to the abundance of land crabs, which considerably reduce the extent of the litter layer on the forest floor.


Assuntos
Dictyosteliida/classificação , Dictyosteliida/isolamento & purificação , Filogenia , Solo , Austrália , Oceano Índico
8.
Sci Rep ; 9(1): 5, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626889

RESUMO

Dictyostelid cellular slime molds (dictyostelids) are key components of soil microbes. The Qinghai-Tibet Plateau is characterized by unique and important forest types because of the considerable range in elevation which exists. During the period of 2012, 2013 and 2016, 12 species of dictyostelids were yielded from samples collected in this region, including two new species and three new records for China. Six other species were new records for this region. Ontogeny, morphology, ultrastructure and systematic molecular analyses (SSU & ITS) of D. minimum and D. multiforme confirm that they are Goup 4 new species. The ornamentation of the surface of dictyostelids' spores is the first time to be observed until now. In the SSU phylogenetic tree generated in the present study, Synstelium, not assigned to order and family before, was assigned to the clade Acytosteliaceae in the Acytosteliales firstly. To our knowledge, the study reported herein is the first investigation of dictyostelid biodiversity carried out at elevations above 2000 m. Sorocarp size, sorus size, spore length, ratio of sorus and sorophore, and ratio of sorus and spore size were positively correlated with increasing elevation and no linear correlated with forest type, according to the results of linear regression analysis.


Assuntos
Dictyosteliida/classificação , Dictyosteliida/ultraestrutura , Biodiversidade , China , Ecossistema , Filogenia , Microbiologia do Solo , Tibet
9.
BMC Evol Biol ; 18(1): 198, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577752

RESUMO

BACKGROUND: Dictyostelid cellular slime molds (dictyostelids) are common inhabitants of the soil and leaf litter layer of fields and forests, along with animal dung, where they feed mostly on bacteria. However, reports on the species diversity of dictyostelids in South Asia, particularly Thailand, are limited. The research reported in this paper was carried out to increase our knowledge of the species diversity of this group of organisms in northern Thailand. RESULTS: Forty soil samples were collected at four localities in northern Thailand to assess the species richness of dictyostelids. These samples yielded five dictyostelid isolates that were not morphologically consistent with any described species. Based on molecular signatures, all five of these isolates were assigned to the family Cavenderiaceae, genus Cavenderia. All five share a number of morphological similarities with other known species from this family. The new taxa differ from previously described species primarily in the size and complexity of their fruiting bodies (sorocarps). This paper describes these new species (Cavenderia aureostabilis, C. bhumiboliana, C. protodigitata, C. pseudoaureostipes, and C. subdiscoidea) based on a combination of morphological characteristics and their phylogenetic positions. CONCLUSIONS: At least 15 taxa of dictyostelids were obtained from the four localities in northern Thailand, which indicates the high level of species diversity in this region. Five species were found to be new to science. These belong to the family Cavenderiaceae, genus Cavenderia, and were described based on both morphology and phylogeny.


Assuntos
Amoeba/classificação , Dictyosteliida/classificação , Animais , Filogenia , Especificidade da Espécie , Tailândia
10.
Annu Rev Microbiol ; 72: 293-307, 2018 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-29924686

RESUMO

Sex in social amoebae (or dictyostelids) has a number of striking features. Dictyostelid zygotes do not proliferate but grow to a large size by feeding on other cells of the same species, each zygote ultimately forming a walled structure called a macrocyst. The diploid macrocyst nucleus undergoes meiosis, after which a single meiotic product survives to restart haploid vegetative growth. Meiotic recombination is generally initiated by the Spo11 enzyme, which introduces DNA double-strand breaks. Uniquely, as far as is known among sexual eukaryotes, dictyostelids lack a SPO11 gene. Despite this, recombination occurs at high frequencies during meiosis in dictyostelids, through unknown mechanisms. The molecular processes underlying these events, and the evolutionary drivers that brought them into being, may shed light on the genetic conflicts that occur within and between genomes, and how they can be resolved.


Assuntos
Dictyosteliida/enzimologia , Dictyosteliida/crescimento & desenvolvimento , Endodesoxirribonucleases/genética , Meiose , DNA de Protozoário/genética , DNA de Protozoário/metabolismo , Dictyosteliida/genética , Recombinação Genética
11.
ACS Chem Biol ; 13(6): 1506-1513, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29792671

RESUMO

Among the amoebozoan species capable of forming fruiting bodies, the dictyostelid social amoebae stand out since they form true multicellular organisms by means of single cell aggregation. Upon food depletion, cells migrate across gradients of extracellular signals initiated by cells in aggregation centers. The model species that is widely used to study multicellular development of social amoebae, Dictyostelium discoideum, uses cyclic adenosine monophosphate (cAMP) as a chemoattractant to coordinate aggregation. Molecular phylogeny studies suggested that social amoebae evolved in four major groups, of which groups 1 and 2 are paraphyletic to groups 3 and 4. During early development, intercellular communication with cAMP appears to be restricted to group 4 species. Cells of group 1 and 2 taxa do not respond chemotactically to extracellular cAMP and likely use a dipeptide chemoattractant known as glorin ( N-propionyl-γ-L-glutamyl-L-ornithin-δ-lactam-ethylester) to regulate aggregation. Directional migration of glorin-responsive cells requires the periodic breakdown of the chemoattractant. Here, we identified an extracellular enzymatic activity (glorinase) in the glorin-responsive group 2 taxon Polysphondylium pallidum leading to the inactivation of glorin. We determined the inactivation mechanism to proceed via hydrolytic ethyl ester cleavage of the γ-glutamyl moiety of glorin. Synthetic glorinamide, in which the ethyl ester group was substituted by an ethyl amide group, had glorin-like biological activity but was resistant to degradation by glorinase. Our observations pave the way for future investigations toward an ancient eukaryotic chemotaxis system.


Assuntos
Fatores Quimiotáticos/metabolismo , Dictyosteliida/metabolismo , Dipeptídeos/metabolismo , Ésteres/metabolismo , Lactamas/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Fatores Quimiotáticos/química , Dictyosteliida/crescimento & desenvolvimento , Dipeptídeos/química , Ésteres/química , Hidrólise , Lactamas/química , Proteínas de Protozoários/metabolismo
12.
Proc Natl Acad Sci U S A ; 115(14): E3201-E3210, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29555751

RESUMO

AID/APOBEC deaminases (AADs) convert cytidine to uridine in single-stranded nucleic acids. They are involved in numerous mutagenic processes, including those underpinning vertebrate innate and adaptive immunity. Using a multipronged sequence analysis strategy, we uncover several AADs across metazoa, dictyosteliida, and algae, including multiple previously unreported vertebrate clades, and versions from urochordates, nematodes, echinoderms, arthropods, lophotrochozoans, cnidarians, and porifera. Evolutionary analysis suggests a fundamental division of AADs early in metazoan evolution into secreted deaminases (SNADs) and classical AADs, followed by diversification into several clades driven by rapid-sequence evolution, gene loss, lineage-specific expansions, and lateral transfer to various algae. Most vertebrate AADs, including AID and APOBECs1-3, diversified in the vertebrates, whereas the APOBEC4-like clade has a deeper origin in metazoa. Positional entropy analysis suggests that several AAD clades are diversifying rapidly, especially in the positions predicted to interact with the nucleic acid target motif, and with potential viral inhibitors. Further, several AADs have evolved neomorphic metal-binding inserts, especially within loops predicted to interact with the target nucleic acid. We also observe polymorphisms, driven by alternative splicing, gene loss, and possibly intergenic recombination between paralogs. We propose that biological conflicts of AADs with viruses and genomic retroelements are drivers of rapid AAD evolution, suggesting a widespread presence of mutagenesis-based immune-defense systems. Deaminases like AID represent versions "institutionalized" from the broader array of AADs pitted in such arms races for mutagenesis of self-DNA, and similar recruitment might have independently occurred elsewhere in metazoa.


Assuntos
Imunidade Adaptativa/imunologia , Citidina Desaminase/classificação , Citidina Desaminase/genética , Evolução Molecular , Ácidos Nucleicos/genética , Vertebrados/imunologia , Vírus/patogenicidade , Sequência de Aminoácidos , Animais , Clorófitas/genética , Clorófitas/imunologia , Citidina Desaminase/química , Citidina Desaminase/imunologia , Dictyosteliida/genética , Dictyosteliida/imunologia , Interações Hospedeiro-Patógeno , Humanos , Filogenia , Conformação Proteica , Retroelementos , Homologia de Sequência , Vertebrados/genética , Vertebrados/virologia
13.
Protist ; 169(1): 1-28, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29367151

RESUMO

Traditional morphology-based taxonomy of dictyostelids is rejected by molecular phylogeny. A new classification is presented based on monophyletic entities with consistent and strong molecular phylogenetic support and that are, as far as possible, morphologically recognizable. All newly named clades are diagnosed with small subunit ribosomal RNA (18S rRNA) sequence signatures plus morphological synapomorphies where possible. The two major molecular clades are given the rank of order, as Acytosteliales ord. nov. and Dictyosteliales. The two major clades within each of these orders are recognized and given the rank of family as, respectively, Acytosteliaceae and Cavenderiaceae fam. nov. in Acytosteliales, and Dictyosteliaceae and Raperosteliaceae fam. nov. in Dictyosteliales. Twelve genera are recognized: Cavenderia gen. nov. in Cavenderiaceae, Acytostelium, Rostrostelium gen. nov. and Heterostelium gen. nov. in Acytosteliaceae, Tieghemostelium gen. nov., Hagiwaraea gen. nov., Raperostelium gen. nov. and Speleostelium gen. nov. in Raperosteliaceae, and Dictyostelium and Polysphondylium in Dictyosteliaceae. The "polycephalum" complex is treated as Coremiostelium gen. nov. (not assigned to family) and the "polycarpum" complex as Synstelium gen. nov. (not assigned to order and family). Coenonia, which may not be a dictyostelid, is treated as a genus incertae sedis. Eighty-eight new combinations are made at species and variety level, and Dictyostelium ammophilum is validated.


Assuntos
Dictyosteliida/classificação , DNA de Protozoário/genética , DNA Ribossômico/genética , Dictyosteliida/genética , Dictyosteliida/crescimento & desenvolvimento , Dictyosteliida/isolamento & purificação , Filogenia , RNA Ribossômico 18S/genética
14.
J Nat Prod ; 80(10): 2716-2722, 2017 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-28921976

RESUMO

Eight chlorinated alkylresorcinols, monochasiol A-H (1-8), were isolated from the fruiting bodies of Dictyostelium monochasioides. Compounds 1-8 were synthesized to confirm their structures and to obtain sufficient material for performing biological tests. Monochasiol A (1) selectively inhibited the concanavalin A-induced interleukin-2 production in Jurkat cells, a human T lymphocyte cell line. Monochasiols were biogenetically synthesized by the combination of biosynthetic enzymes relating to the principal polyketides, MPBD and DIF-1, produced by Dictyostelium discoideum.


Assuntos
Dictyostelium/química , Hidrocarbonetos Clorados , Resorcinóis , Sobrevivência Celular/efeitos dos fármacos , Concanavalina A/farmacologia , Dictyosteliida/química , Células HeLa , Hexanonas/metabolismo , Humanos , Hidrocarbonetos Clorados/química , Hidrocarbonetos Clorados/isolamento & purificação , Hidrocarbonetos Clorados/farmacologia , Interleucina-2/biossíntese , Células Jurkat , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Policetídeos/metabolismo , Resorcinóis/química , Resorcinóis/isolamento & purificação , Resorcinóis/farmacologia
15.
Protist ; 168(3): 311-325, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28499132

RESUMO

Dictyostelids are free-living phagocytes that feed on bacteria in diverse habitats. When bacterial prey is in short supply or depleted, they undergo multicellular development culminating in the formation of dormant spores. In this work, we tested isolates representing four dictyostelid species from two genera (Dictyostelium and Polysphondylium) for the potential to feed on biofilms preformed on glass and polycarbonate surfaces. The abilities of dictyostelids were monitored for three hallmarks of activity: 1) spore germination on biofilms, 2) predation on biofilm enmeshed bacteria by phagocytic cells and 3) characteristic stages of multicellular development (streaming and fructification). We found that all dictyostelid isolates tested could feed on biofilm enmeshed bacteria produced by human and plant pathogens: Klebsiella oxytoca, Pseudomonas aeruginosa, Pseudomonas syringae, Erwinia amylovora 1189 (biofilm former) and E. amylovora 1189 Δams (biofilm deficient mutant). However, when dictyostelids were fed planktonic E. amylovora Δams the bacterial cells exhibited an increased susceptibility to predation by one of the two dictyostelid strains they were tested against. Taken together, the qualitative and quantitative data presented here suggest that dictyostelids have preferences in bacterial prey which affects their efficiency of feeding on bacterial biofilms.


Assuntos
Biofilmes , Dictyosteliida/fisiologia , Erwinia amylovora/fisiologia , Cadeia Alimentar , Klebsiella oxytoca/fisiologia , Pseudomonas/fisiologia , Dictyostelium/fisiologia
16.
Genome Biol Evol ; 8(9): 2663-71, 2016 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-27189989

RESUMO

The emergence of the nucleus was a major event of eukaryogenesis. How the nuclear envelope (NE) arose and acquired functions governing chromatin organization and epigenetic control has direct bearing on origins of developmental/stage-specific expression programs. The configuration of the NE and the associated lamina in the last eukaryotic common ancestor (LECA) is of major significance and can provide insight into activities within the LECA nucleus. Subsequent lamina evolution, alterations, and adaptations inform on the variation and selection of distinct mechanisms that subtend gene expression in distinct taxa. Understanding lamina evolution has been difficult due to the diversity and limited taxonomic distributions of the three currently known highly distinct nuclear lamina. We rigorously searched available sequence data for an expanded view of the distribution of known lamina and lamina-associated proteins. While the lamina proteins of plants and trypanosomes are indeed taxonomically restricted, homologs of metazoan lamins and key lamin-binding proteins have significantly broader distributions, and a lamin gene tree supports vertical evolution from the LECA. Two protist lamins from highly divergent taxa target the nucleus in mammalian cells and polymerize into filamentous structures, suggesting functional conservation of distant lamin homologs. Significantly, a high level of divergence of lamin homologs within certain eukaryotic groups and the apparent absence of lamins and/or the presence of seemingly different lamina proteins in many eukaryotes suggests great evolutionary plasticity in structures at the NE, and hence mechanisms of chromatin tethering and epigenetic gene control.


Assuntos
Evolução Molecular , Laminas/genética , Lâmina Nuclear/genética , Animais , Dictyosteliida/classificação , Dictyosteliida/genética , Células HEK293 , Humanos , Laminas/química , Lâmina Nuclear/metabolismo , Filogenia , Phytophthora infestans/classificação , Phytophthora infestans/genética , Polimorfismo Genético , Proteínas de Protozoários/química , Proteínas de Protozoários/genética
17.
Mycologia ; 108(1): 80-109, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26490703

RESUMO

Two series of samples collected for isolation of dictyostelid cellular slime molds (dictyostelids) in Madagascar yielded a relatively large number of isolates of Polysphondylium. Most of these turned out to be species new to science that show varying degrees of clustering from unclustered to coremiform as well as an ability to migrate. Migratory ability (phototaxis) is a common feature of species assigned to Group 2 of the Polysphondylia and is common in the new species from Madagascar. Another common feature, clustering, appears to be a strategy for keeping fruiting bodies erect for a longer time in a climate that is relatively dry, whereas migratory ability may function seasonally when there is more rainfall. Thirteen species are described herein. Each of these is characterized by a particular set of distinguishing features, and collectively they expand our concept of the genus Polysphondylium.


Assuntos
Dictyosteliida/classificação , Sequência de Bases , DNA de Protozoário/química , DNA de Protozoário/genética , Dictyosteliida/citologia , Dictyosteliida/genética , Geografia , Madagáscar , Dados de Sequência Molecular , Filogenia , Esporos de Protozoários
18.
Med Chem ; 11(7): 666-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25925558

RESUMO

The diisopentenyloxy quinolobactin derivative 3-methylbut-2-enyl-4-methoxy-8-[(3-methylbut-2-enyl)oxy] quinoline-2-carboxylate, also named as Ppc-1, has been initially isolated from the fruiting bodies of the cellular slime mold Polysphondylium pseudo-candidum. Given that few data are available in the literature concerning the biological properties of this compound, this study was undertaken to evaluate its antibacterial and anti-inflammatory properties. Ppc-1 exerted antibacterial activity on the Gram negative periodontopathogen Porphyromonas gingivalis, while it had no such effect on the other bacterial species tested. The antibacterial activity of Ppc-1 appeared to result from its ability to permeate the cell membrane. Using the U937-3xκB-LUC human monocytic cell line, Ppc-1 was found to dose-dependently inhibit the lipopolysaccharide-induced NF-κB activation, a signaling pathway that has been associated with inflammatory mediator secretion. In conclusion, Ppc-1, by exhibiting a dual mode of action including antibacterial and anti-inflammatory activities, may represent a promising targeted therapeutic agent for periodontal diseases.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Dictyosteliida/química , Hemiterpenos/farmacologia , Quinolinas/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo
19.
PLoS One ; 10(2): e0117088, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25668511

RESUMO

Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived from slime molds and other microorganisms for their effects on mitochondrial oxygen consumption. We identified Ppc-1 as a novel molecule which stimulates oxygen consumption without adverse effects on ATP production. The kinetic behavior of Ppc-1 suggests its function as a mitochondrial uncoupler. Serial administration of Ppc-1 into mice suppressed weight gain with no abnormal effects on liver or kidney tissues, and no evidence of tumor formation. Serum fatty acid levels were significantly elevated in mice treated with Ppc-1, while body fat content remained low. After a single administration, Ppc-1 distributes into various tissues of individual animals at low levels. Ppc-1 stimulates adipocytes in culture to release fatty acids, which might explain the elevated serum fatty acids in Ppc-1-treated mice. The results suggest that Ppc-1 is a unique mitochondrial regulator which will be a valuable tool for mitochondrial research as well as the development of new drugs to treat obesity.


Assuntos
Dictyosteliida/metabolismo , Mitocôndrias/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Perda de Peso/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Ácidos Graxos/metabolismo , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/metabolismo , Consumo de Oxigênio/efeitos dos fármacos
20.
Dev Growth Differ ; 56(7): 526-33, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25208883

RESUMO

Cellulose is a major and important component of the extracellular matrix during the development of Dictyostelium discoideum. Upon starvation, solitary amoebae of D. discoideum gather and form fruiting bodies in which cells differentiate into stalk cells and spores. The stalk tubes and walls of spores and stalk cells are made of cellulose. In the genus Acytostelium, however, all cells are destined to become spores and the stalks comprise only a cellulose tube, suggesting species-specific regulation of cellulose synthesis. In this study, we cloned a putative cellulose synthase gene (cesA) of Acytostelium subglobosum and performed comparative analyses with the D. discoideum cellulose synthase gene (dcsA). Although the deduced amino acid sequences were highly conserved between cesA and dcsA, the numbers of transmembrane spans preceding the catalytic domain were dissimilar; 2 and 3, respectively. Since ectopic expression of cesA in dcsA(-) null cells failed to restore the developmental defects of the mutant, we constructed a series of chimerical genes for complementation analyses and found that the catalytic domain of cesA was functional in D. discoideum cells if the preceding transmembrane region was swapped with dcsA. The non-functional products that contained the cesA-derived transmembrane region were localized to lysosomes. These results indicate that the transmembrane region of cellulose synthase is essential for proper accumulation of cellulose during the development of D. discoideum and that its differential localization in A. subglobosum may be related to the characteristic morphogenesis in this species.


Assuntos
Celulose/biossíntese , Dictyosteliida/enzimologia , Dictyosteliida/crescimento & desenvolvimento , Glucosiltransferases/genética , Morfogênese/fisiologia , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Sequência Conservada/genética , Teste de Complementação Genética , Vetores Genéticos/genética , Glucosiltransferases/metabolismo , Immunoblotting , Microscopia de Fluorescência , Dados de Sequência Molecular , Morfogênese/genética , Reprodução/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Especificidade da Espécie
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