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PubMedDate not supplied

[The role of the mononuclear phagocyte system in regulating protein biosynthesis in rat organs and tissues in ontogeny].

In experiments on Wistar rats, we demonstrate that activation of mononuclear phagocytes by a lipopolysaccharide (prodigiosin) results in a marked increase of protein biosynthesis in various organs and tissues. This control mechanism is most distinct in mature rats and undergoes involution in older rats. Cell elements in the mononuclear phagocytes (resident macrophages) originate from the bone marrow. Decrease in the reserve capacity of the bone marrow with age in response to prodigiosin administration suggests an important role of this mechanism during aging.

Aging↗
PubMed1983

Cloning of a Streptomyces gene for an O-methyltransferase involved in antibiotic biosynthesis.

The red pigmented antibiotic of Streptomyces coelicolor A3(2) is chemically very similar to the Serratia marcescens pigment, prodigiosin. We have demonstrated by co-synthesis experiments between non-producing mutants of both species that their biosynthetic pathways are similar, and have discovered identities between specific mutants of each organism. Molecular cloning techniques have been employed in order to isolate Streptomyces chromosomal DNA segments which "complement" a mutant defective in the penultimate step of the red biosynthetic pathway: an O-methyltransferase enzyme. In one case, the lesion appears to be repaired by integrative recombination into the chromosome; another case may represent expression from the autonomously replicating recombinant plasmid.

Anti-Bacterial Agents↗
PubMed2005

Potent in vitro anticancer activity of metacycloprodigiosin and undecylprodigiosin from a sponge-derived actinomycete Saccharopolyspora sp. nov.

Bioassay-guided fractionation of CHCl3 extract from the fermentation broth of a sponge Mycale plumose-derived actinomycete Saccharopolyspora sp. nov., led to the isolation of two known prodigiosin analogs--metacycloprodigiosin (1) and undecylprodigiosin (2). These compounds exhibited significant cytotoxic activities against five cancer cell lines: P388, HL60, A-549, BEL-7402, and SPCA4. This is the first report on the significant cytotoxicity of metacycloprodigiosin (1) against human cancer cell lines.

Animals↗
PubMed2006

Producing mechanism of an algicidal compound against red tide phytoplankton in a marine bacterium gamma-proteobacterium.

Strain MS-02-063, gamma-proteobacterium, isolated from a coast area of Nagasaki, Japan, produced a red pigment which belongs to prodigiosin members. This pigment, PG-L-1, showed potent algicidal activity against various red tide phytoplanktons in a concentration-dependent manner. An understanding of a mechanism of PG-L-1 production by this marine bacterium may yield important new insights and strategies for preventing blooms of harmful flagellate algae in natural marine environments. Therefore, we analyzed the mechanisms of PG-L-1 production. In our previous study, the pigment production by this marine bacterium was completely inhibited at 1.56 microg/ml of erythromycin or 3.13 microg/ml of chloramphenicol, while minimal inhibitory concentrations for cell growth of erythromycin and chloramphenicol against this bacterium were >100 and 25 microg/ml, respectively. It is interesting to note that the ability of the pigment production in erythromycin-treated bacterium recovered by an addition of homoserine lactone. In fact, the pigment production was inhibited by beta-cyclodextrin that inhibits autoinducer activities by a complex with N-acyl homoserine lactones. N-acyl homoserine lactones with autoinducer activities are ubiquitous bacterial signaling molecules that regulate gene expression in a cell density dependent process known as quorum sensing. Therefore, it was suggested that PG-L-1 produced by strain MS-02-063 is controlled by the homoserine lactone quorum sensing. It is speculated that this quorum sensing is involved in the production of algicidal agents of other marine bacteria. This bacterium and other algicidal bacteria might be concerned in regulating the blooms of harmful flagellate algae through the quorum sensing system.

Animals↗
PubMed2005

Gut microbiota and parasite transmission by insect vectors.

In the gut of some insect vectors, parasites ingested with the bloodmeal decrease in number before coming into contact with host tissues. Many factors could be responsible for this reduction in parasite number but the potentially important role of the large communities of naturally occurring microorganisms that exist alongside the newly ingested parasites in the vector midgut has been largely overlooked. Some previous reports exist of the inhibition of parasite development by vector gut microbiota and of the killing of Trypanosoma cruzi and Plasmodium spp. by prodigiosin produced by bacteria. Based on this evidence, we believe that the microbiota present in the midgut of vector insects could have important roles as determinants of parasite survival and development in insect vector hosts and, therefore, contribute to the modulation of vector competence for many important diseases.

Animals↗
PubMed1997

Characterization of a series of vacuolar type H(+)-ATPase inhibitors on CTL-mediated cytotoxicity.

Four vacuolar type H(+)-ATPase (V-ATPase) inhibitors, i.e. concanamycin A (CMA), bafilomycin A1 (BMA), destruxin E (DRE) and prodigiosin 25-C (PRG) profoundly blocked the perforin-dependent cytotoxicity mediated by CD8+ CTL clone. Cytoplasmic acidic compartments were not detected under fluorescent microscopy after treatment of the cells with these V-ATPase inhibitors. In the lytic granule fractions, BMA, CMA, DRE and PRG completely abrogated the perforin activity, although these drugs slightly decreased the granzyme A activity. Under the same conditions, BMA and CMA markedly reduced the perforin content, while DRE and PRG had no significant effects as assayed by immunoblotting using anti-perforin antibody. These data suggest that perforin is predominantly inactivated even without proteolysis in DRE- or PRG-treated cells. We propose that acidic pH is essential to maintain not only quantity but also quality of perform in the lytic granules.

Animals↗
PubMed2000

Effect of some antibiotics on pigmentation in Serratia marcescens.

Serratia marcescens is characterized by its ability to produce a red pigment called prodigiosin. It is well known that there are some substances affecting pigmentation in bacteria. Cefoxitin, erythromycin, tobramycin, co-trimoxazole, imipenem and nitrofurantoin were found to have an inhibitory effect on pigmentation in a S. marcescens strain isolated from urine. It was also shown that the LD50 dose determined by inoculation of eight-week-old BALB/c mice with serial dilutions of overnight cultures of pigmented and nonpigmented variants was lower (LD50 = 300 x 10(3.94)) in the nonpigmented variant than in the pigmented one (LD50 = 300 x 10(5.58)). In addition, the Sereny test showed that in contrast to the pigmented variant, the nonpigmented variant caused keratitis in guinea pig eye.

Animals↗
PubMed1996

Strains of the genus Serratia as beneficial rhizobacteria of oilseed rape with antifungal properties.

Isolates of Serratia have been isolated from the rhizosphere of oilseed rape. The percentage of Serratia in this microenvironment was determined as 12.4% of the total antifungal bacteria. Serratia liquefaciens, S. plymuthica and S. rubidaea were found. All of the isolates showed an antifungal activity against different phytopathogenic fungi in vitro but the efficiency of strains was different. The antifungal mechanisms of 18 selected strains were investigated. Direct antifungal effect may be based on antibiosis (production of prodigiosin and pyrrolnitrin) and production of lytic enzymes (chitinases and beta-1,3-glucanases). Potent siderophores were secreted by the strains to improve the availability of iron. No strain was able to produce cyanide. Most of the strains secrete the plant growth hormone indole-acetic-acid which can directly promote the growth of roots. The mechanisms were specific for each isolate.

Acetic Acid↗
PubMed2006

The biosynthesis and regulation of bacterial prodiginines.

The red-pigmented prodiginines are bioactive secondary metabolites produced by both Gram-negative and Gram-positive bacteria. Recently, these tripyrrole molecules have received renewed attention owing to reported immunosuppressive and anticancer properties. The enzymes involved in the biosynthetic pathways for the production of two of these molecules, prodigiosin and undecylprodigiosin, are now known. However, the biochemistry of some of the reactions is still poorly understood. The physiology and regulation of prodiginine production in Serratia and Streptomyces are now well understood, although the biological role of these pigments in the producer organisms remains unclear. However, research into the biology of pigment production will stimulate interest in the bioengineering of strains to synthesize useful prodiginine derivatives.

Antineoplastic Agents↗
PubMed1997

The rap and hor proteins of Erwinia, Serratia and Yersinia: a novel subgroup in a growing superfamily of proteins regulating diverse physiological processes in bacterial pathogens.

The enteric bacterium Serratia marcescens is an opportunistic human pathogen. The strain ATCC39006 makes the red pigment, prodigiosin (Pig), and the beta-lactam antibiotic carbapenem (Car). Mutants were isolated that were concomitantly defective for Pig and Car production. These mutants were found to have a mutation in the rap gene (Regulation of Antibiotic and Pigment). Sequence analysis of the rap gene revealed a predicted protein product showing strong homology to SlyA, originally thought to be a haemolytic virulence determinant in Salmonella typhimurium. Homologues of rap were detected in several bacterial genera, including Salmonella, Yersinia, Enterobacter, and species of the plant pathogen, Erwinia. The Erwinia hoeEr (homologue of rap) and the Yersinia horYe genes were also found to be very similar to rap and slyA. Marker exchange mutagenesis of horEr revealed that it encoded a regulatory protein controlling the production of antibiotic and exoenzyme virulence determinants in the phytopathogen, Erwinia carotovora subspecies carotovora. We have shown that these new homologues of SlyA form a highly conserved subgroup of a growing superfamily of bacterial regulatory proteins controlling diverse physiological processes in human, animal and plant pathogens.

Amino Acid Sequence↗
PubMed2005

Genomic blueprint of Hahella chejuensis, a marine microbe producing an algicidal agent.

Harmful algal blooms, caused by rapid growth and accumulation of certain microalgae in the ocean, pose considerable impacts on marine environments, aquatic industries and even public health. Here, we present the 7.2-megabase genome of the marine bacterium Hahella chejuensis including genes responsible for the biosynthesis of a pigment which has the lytic activity against a red-tide dinoflagellate. H.chejuensis is the first sequenced species in the Oceanospiralles clade, and sequence analysis revealed its distant relationship to the Pseudomonas group. The genome was well equipped with genes for basic metabolic capabilities and contained a large number of genes involved in regulation or transport as well as with characteristics as a marine heterotroph. Sequence analysis also revealed a multitude of genes of functional equivalence or of possible foreign origin. Functions encoded in the genomic islands include biosynthesis of exopolysacchrides, toxins, polyketides or non-ribosomal peptides, iron utilization, motility, type III protein secretion and pigmentation. Molecular structure of the algicidal pigment, which was determined through LC-ESI-MS/MS and NMR analyses, indicated that it is prodigiosin. In conclusion, our work provides new insights into mitigating algal blooms in addition to genetic make-up, physiology, biotic interactions and biological roles in the community of a marine bacterium.

Adaptation, Physiological↗
PubMed2003

Zooshikella ganghwensis gen. nov., sp. nov., isolated from tidal flat sediments.

Two red pigment-producing bacterial strains with a metallic green sheen were isolated from a sediment sample of getbol, the Korean tidal flat. Phylogenetic analysis based on 16S rDNA sequences showed that these isolates represent a phyletic lineage within the gamma-Proteobacteria that is distantly related to the genus Hahella. No bacterial species with validly published names showed > or = 92% 16S rRNA similarity with the getbol isolates. The strains were gram-negative, chemo-organotrophic, aerobic and required NaCl (1-7%) for growth. They produced pigments with maximum absorption at 540 nm, which indicated the presence of prodigiosin, a well-known red pigment previously detected in Serratia marcescens. The major isoprenoid quinone was ubiquinone-9. The predominant cellular fatty acids were saturated and monounsaturated straight-chain fatty acids. The DNA G + C contents ranged from 40 to 42 mol%. The combination of physiological, biochemical and chemotaxonomic data clearly separated the test strains from other phylogenetically related genera in the gamma-Proteobacteria. On the basis of polyphasic evidence from this study, it is proposed that the two getbol isolates should be classified in a novel genus, Zooshikella gen. nov., as Zooshikella ganghwensis sp. nov.

Fatty Acids↗
PubMed2006

Metabolic and regulatory engineering of Serratia marcescens: mimicking phage-mediated horizontal acquisition of antibiotic biosynthesis and quorum-sensing capacities.

Serratia marcescens is an important cause of opportunistic human infections. Many, but not all, strains produce prodigiosin, a secondary metabolic, red-pigment antibiotic, the biosynthesis of which is directed by the pig gene cluster. Quorum sensing (QS) involves the production and detection of chemical signal molecules as a means to regulate gene expression in response to population cell density. Several strains of S. marcescens have previously been shown to possess an N-acyl-L-homoserine lactone (aHSL) QS system. This study aimed to determine the impact of introducing, by phage-mediated horizontal gene transfer, a biosynthetic gene cluster (pig) and a regulatory locus (aHSL QS) into strains lacking the respective trait. The pig cluster from S. marcescens ATCC 274 (Sma 274) was transferred to the non-pigmented strain, S. marcescens strain 12 (Sma 12). In the engineered strain, pigment was expressed and brought under the control of the recipient's native regulatory systems (aHSL QS and luxS). Moreover, transfer of the aHSL locus from Sma 12 to the non-QS Sma 274 resulted in the imposition of aHSL control onto a variety of native traits, including pigment production. In addition, during this study, the QS regulon of the clinical strain, Sma 12, was characterized, and some novel QS-regulated traits in S. marcescens were identified. The results have implications for the evolution and dissemination of biosynthetic and QS loci, illustrating the genetic modularity and ease of acquisition of these traits and the capacity of phages to act as vectors for horizontal gene transfer.

Anti-Bacterial Agents↗
PubMed2005

Enhanced undecylprodigiosin production from Serratia marcescens SS-1 by medium formulation and amino-acid supplementation.

Serratia marcescens Simon Swift-1 (SS-1) was used to produce a prodigiosin-like pigment, undecylprodigiosin (UP), known to have antitumor activities and potential as an anticancer drug. Modified media containing components of Luria-Bertani (LB) broth and selected amino acids were used to improve UP production from S. marcescens SS-1. Optimal culture conditions (e.g., temperature, pH, agitation rate) for UP production were also identified. It was found that S. marcescens SS-1 was able to produce 690 mg l-1 of UP when it was grown with 5 g l-1 yeast extract alone (YE medium) under the optimal culture conditions of 30 degrees C, 200 rpm, and pH 8. The UP production of 690 mg l-1 is nearly 23-fold of that obtained from original LB medium. Addition of amino acids containing pyrrole-like structures further enhanced UP production. Nearly 2 and 1.4 g l-1 of UP was produced when the SS-1 strain was cultivated with YE medium supplemented with proline and histidine (5 g l-1), respectively. Moreover, the addition of aspartic acid (5 g l-1) also resulted in a high UP production of 1.4 g l-1. Optimal dosages of the three amino acids were subsequently determined and the highest UP production (2.5 g l-1) was achieved with the addition of 10 g l-1 of proline. This suggests that the supplementation of amino acids related to the formation of a UP precursor (e.g., pyrrolylpyrromethene) could enhance UP production by the SS-1 strain.

Amino Acids↗
PubMed1999

Fatty acid profiles in pigmented and non-pigmented strains of S. marcescens.

Wild, pigmented strains of Serratia marcescens and their non-pigmented mutants were compared on the basis of fatty acid profiles and lipid content. Classic biochemical tests show only minor differences, as well as fatty acid ratio C18:C16. The total amount of lipid synthesized and the saturated/unsaturated fatty acids ratio disclose a sharp total lipid reduction and a high percentage of unsaturated fatty acids in the pigmented strains, placing them in separated clusters compared with the nonpigmented mutants. It is hypothesized that the synthesis of the polyacetate required for the completion of the prodigiosin molecule may result in waste of methyl groups and thus affect the total amount of lipids.

Chromatography, Gas↗
PubMed1999

New immunosuppressive drug PNU156804 blocks IL-2-dependent proliferation and NF-kappa B and AP-1 activation.

We had previously shown that the drug undecylprodigiosin (UP) blocks human lymphocyte proliferation in vitro. We have now investigated the mechanism of action of a new analogue of UP, PNU156804, which shows a more favorable activity profile than UP in mice. We demonstrate here that the biological effect of PNU156804 in vitro is indistinguishable from UP: PNU156804 blocks human T cell proliferation in mid-late G1, as determined by cell cycle analysis, expression of cyclins, and cyclin-dependent kinases and retinoblastoma phosphorylation. In addition, we show that PNU156804 does not block significantly the induction of either IL-2 or IL-2R alpha- and gamma-chains but inhibits IL-2-dependent T cell proliferation. We have investigated several molecular pathways that are known to be activated by IL-2 in T cells. We show that PNU156804 does not inhibit c-myc and bcl-2 mRNA induction. On the other hand, PNU156804 efficiently inhibits the activation of the NF-kappa B and AP-1 transcription factors. PNU156804 inhibition of NF-kappa B activation is due to the inhibition of the degradation of I kappa B-alpha and I kappa B-beta. PNU156804 action is restricted to some signaling pathways; it does not affect NF-kappa B activation by PMA in T cells but blocks that induced by CD40 cross-linking in B lymphocytes. We conclude that the prodigiosin family of immunosuppressants is a new family of molecules that show a novel target specificity clearly distinct from that of other immunosuppressive drugs such as cyclosporin A, FK506, and rapamycin.

B-Lymphocytes↗
PubMed2002

Uptake of nickel (II) by Serratia marcescens.

Bioaccumulation and biosorption of various nickel salts by Serratia marcescens (NCIM 2078) were investigated Biosorption of nickel was found maximum for the nickel nitrate and nickel chloride as 28.08 and 25.51 mg-1 nickel was obtained in dry biomass of S. marcescens, respectively. The possible role of pigment prodigiosin in uptake of nickel is discussed.

Biomass↗